Effect of Spermidine on Endothelial Function in Systemic Lupus Erythematosus Mice.

Endothelial dysfunction is common in Systemic Lupus Erythematosus (SLE), even in the absence of cardiovascular disease. Evidence suggests that impaired mitophagy contributes to SLE. Mitochondrial dysfunction is also associated with impaired endothelial function. Spermidine, a natural polyamine, stimulates mitophagy by the PINK1-parkin pathway and counters age-associated endothelial dysfunction. However, the effect of spermidine on mitophagy and vascular function in SLE has not been explored. To address this gap, 9-week-old female lupus-prone (MRL/lpr) and healthy control (MRL/MpJ) mice were randomly assigned to spermidine treatment (lpr_Spermidine and MpJ_Spermidine) for 8 weeks or as control (lpr_Control and MpJ_Control). lpr_Control mice exhibited impaired endothelial function (e.g., decreased relaxation to acetylcholine), increased markers of inflammation, and lower protein content of parkin, a mitophagy marker, in the thoracic aorta. Spermidine treatment prevented endothelial dysfunction in MRL-lpr mice. Furthermore, aortas from lpr_Spermidine mice had lower levels of inflammatory markers and higher levels of parkin. Lupus phenotypes were not affected by spermidine. Collectively, these results demonstrate the beneficial effects of spermidine treatment on endothelial function, inflammation, and mitophagy in SLE mice. These results support future studies of the beneficial effects of spermidine on endothelial dysfunction and cardiovascular disease risk in SLE.

A Proteomic Approach to Understand the Clinical Significance of Acute Myeloid Leukemia-Derived Extracellular Vesicles Reflecting Essential Characteristics of Leukemia.

Extracellular vesicle (EV) proteins from acute myeloid leukemia (AML) cell lines were analyzed using mass spectrometry. The analyses identified 2450 proteins, including 461 differentially expressed proteins (290 upregulated and 171 downregulated). CD53 and CD47 were upregulated and were selected as candidate biomarkers. The association between survival of patients with AML and the expression levels of CD53 and CD47 at diagnosis was analyzed using mRNA expression data from The Cancer Genome Atlas database. Patients with higher expression levels showed significantly inferior survival than those with lower expression levels. ELISA results of the expression levels of CD53 and CD47 from EVs in the bone marrow of patients with AML at diagnosis and at the time of complete remission with induction chemotherapy revealed that patients with downregulated CD53 and CD47 expression appeared to relapse less frequently. Network model analysis of EV proteins revealed several upregulated kinases, including LYN, CSNK2A1, SYK, CSK, and PTK2B. The potential cytotoxicity of several clinically applicable drugs that inhibit these kinases was tested in AML cell lines. The drugs lowered the viability of AML cells. The collective data suggest that AML cell-derived EVs could reflect essential leukemia biology.

BMI and perceived weight on suicide attempts in Korean adolescents: findings from the Korea Youth Risk Behavior Survey (KYRBS) 2020 to 2021.

BACKGROUND: Suicide is a leading cause of death in South Korea (hereafter 'Korea'), and there is evidence that body weight and perceived weight affecting suicide have a significant effect on suicidal behavior in adolescence. This study investigated the association between body mass index (BMI), perceived weight, and suicide attempts in adolescents. METHODS: We included nationally representative data for a total of 106,320 students in our final analysis. We calculated and stratified BMI (underweight, normal weight, overweight) to determine the correlation between BMI and suicide attempts. We stratified the participants into three groups (perceived as underweight, normal weight, and overweight) for subjective body weight perception to analyze the relationship between subjective body weight perception and suicide attempts. We further analyzed the combination of BMI and subjective body weight perception to determine the relationship between suicide attempts and distorted subjective weight perception. RESULTS: Compared with perceiving oneself as having a normal weight, the odds ratios (ORs) for suicide attempts were significantly increased in the group perceiving themselves as overweight. In addition, those who perceived themselves as overweight but were underweight according to their BMI were at significantly increased risk of suicide attempts relative to those who perceived themselves as about the right weight. CONCLUSIONS: There was a significant association with suicide attempts in the underweight and perceived overweight group. This shows the importance of combining BMI and perceived weight when examining the relationship between weight and suicide attempts in adolescents.

Smooth Muscle-Alpha Actin R149C Pathogenic Variant Downregulates Integrin Recruitment at Cell-Matrix Adhesions and Decreases Cellular Contractility.

Thoracic aortic aneurysm is found in patients with ACTA2 pathogenic variants. ACTA2 missense variants are associated with impaired aortic smooth muscle cell (SMC) contraction. This study tested the hypothesis that the Acta2R149C/+ variant alters actin isoform expression and decreases integrin recruitment, thus, reducing aortic contractility. Stress relaxation measurements in thoracic aortic rings showed two functional regimes with a reduction of stress relaxation in the aorta from Acta2R149C/+ mice at low tension, but not at high tension values. Contractile responses to phenylephrine and potassium chloride were 50% lower in Acta2R149C/+ mice than in wild-type (WT) mice. Additionally, SMC were immunofluorescently labeled for specific proteins and imaged by confocal or total internal reflection fluorescence microscopy. The quantification of protein fluorescence of Acta2R149C/+ SMC showed a downregulation in smooth muscle α-actin (SMα-actin) and a compensatory upregulation of smooth muscle γ-actin (SMγ-actin) compared to WT cells. These results suggest that downregulation of SMα-actin leads to reduced SMC contractility, while upregulation of SMγ-actin may lead to increased SMC stiffness. Decreased α5ß1 and α2ß1 integrin recruitment at cell-matrix adhesions further reduce the ability of mutant cells to participate in cell-matrix crosstalk. Collectively, the results suggest that mutant Acta2R149C/+ aortic SMC have reduced contractility and interaction with the matrix, which are potential long-term contributing factors to thoracic aortic aneurysms.

Associations between ambient air pollution, obesity, and serum vitamin D status in the general population of Korean adults.

BACKGROUND: Although a growing body of evidence suggests air pollution is associated with low serum vitamin D status, few studies have reported whether obesity status affects this relationship. The aim of this study was to identify associations between ambient air pollution exposure, obesity, and serum vitamin D status in the general population of South Korea. METHODS: This study was conducted in a cross-sectional design. A total of 30,242 Korean adults from a nationwide general population survey were included for our final analysis. Air pollutants included particulate matter with an aerodynamic diameter ≤ 10 µm (PM10), nitrogen dioxide (NO2), and carbon monoxide (CO). We measured serum 25-hydroxyvitamin D concentration to assess vitamin D status for each participant. Multiple linear and logistic regression analyses were performed to identify associations between ambient air pollution and vitamin D status in each subgroup according to body mass index level. RESULTS: The annual average concentrations of PM10, NO2, and CO were significantly associated with a lower serum vitamin D concentration and higher risk of vitamin D deficiency. The results show a significant association between serum vitamin D status and PM10 exposure in obese subgroup. Based on the gender, females with obesity showed more strong association (negative) between different air pollutants and low serum vitamin D concentration and a higher risk of vitamin D deficiency. However, this pattern was not observed in men. CONCLUSIONS: This study provides the first evidence that women with obesity may be more vulnerable to vitamin D deficiency in the context of persistent exposure to air pollution.

Comparative Lipidomic Analysis of Extracellular Vesicles Derived from Lactobacillus plantarum APsulloc 331261 Living in Green Tea Leaves Using Liquid Chromatography-Mass Spectrometry.

Lactobacillus plantarum is a popular probiotic species due to its safe and beneficial effects on humans; therefore, novel L. plantarum strains have been isolated and identified from various dietary products. Given that bacteria-derived extracellular vesicles (EVs) have been considered as efficient carriers of bioactive materials and shown to evoke cellular responses effectively, L. plantarum-derived EVs are expected to efficiently elicit health benefits. Herein, we identified L. plantarum APsulloc 331261 living in green tea leaves and isolated EVs from the culture medium. We performed quantitative lipidomic analysis of L. plantarum APsulloc 331261 derived EVs (LEVs) using liquid chromatography-mass spectrometry. In comparison to L. plantarum APsulloc 331261, in LEVs, 67 of 320 identified lipid species were significantly increased and 19 species were decreased. In particular, lysophosphatidylserine(18:4) and phosphatidylcholine(32:2) were critically increased, showing over 21-fold enrichment in LEVs. In addition, there was a notable difference between LEVs and the parent cells in the composition of phospholipids. Our results suggest that the lipidomic profile of bacteria-derived EVs is different from that of the parent cells in phospholipid content and composition. Given that lipids are important components of EVs, quantitative and comparative analyses of EV lipids may improve our understanding of vesicle biogenesis and lipid-mediated intercellular communication within or between living organisms.

Dual effects of duplex RNA harboring 5'-terminal triphosphate on gene silencing and RIG-I mediated innate immune response.

Duplex RNA harboring the 5'-terminal triphosphate RNA is hypothesized to not only execute selective gene silencing via RNA interference, but also induce type I interferon (IFN) through activation of the retinoic acid inducible gene I (RIG-I). We evaluated gene silencing efficacy of the shRNA containing 5'-triphosphate (3p-shRNA) targeting the hepatitis C virus (HCV) RNA genome in hepatic cells. Gene silencing efficacy of the 3p-shRNA was diminished due to the presence of the 5'-triphosphate moiety in shRNA, whereas the shRNA counterpart without 5'-triphosphate (HO-shRNA) showed a strong antiviral activity without significant induction of type I IFN in the cells. 3p-shRNA was observed to be a better activator of the RIG-I signaling than the HO-shRNA with an elevated induction of type I IFN in cells that express RIG-I. Taken together, we suggest that competition for the duplex RNA bearing 5'-triphosphate between RIG-I and RNA interference factors may compromise efficacy of selective gene silencing.

A Herbal Formula, Atofreellage, Ameliorates Atopic Dermatitis-Like Skin Lesions in an NC/Nga Mouse Model.

We evaluated the anti-atopic dermatitis (AD) effect of Atofreellage (AF), a herbal formula composed of 10 medicinal plants. AD was induced on the dorsal skin areas of NC/Nga mice (male, seven weeks old) by daily application of 2,4-dinitrochlorobenzene (DNCB) for five weeks. After three weeks of DNCB application, 200 µL of AF (0, 25, 50 or 100 mg/mL) was applied to the skin lesions. Histological findings, blood cell populations, serum levels of immunoglobulin E (IgE), histamine, pro-inflammatory cytokines, and inflammatory signaling in the skin tissue, and T-helper cell type 2 (Th2)-related cytokines in splenocytes were analyzed. Histopathological findings showed AF treatment notably attenuated the thickness of dorsal skin, and eosinophil infiltration. AF treatment (especially 100 mg/mL) also demonstrably ameliorated the blood cell population abnormalities, as the notable elevation of serum concentrations of IgE, histamine, TNF-α, IL-6 and IL-1ß were remarkably normalized by AF treatment. Western blot analysis evidenced the apparent normalization of inflammatory signals (ERK, p38 MAP kinase, JNK, and NF-κB) in the skin tissue. Additionally, AF treatment notably attenuated the activation of Th2-dominant cytokines (IL-13, IL-4, and IL-5) in Con A-treated splenocytes in an ex vivo assay. In conclusion, this study provides experimental evidence for the clinical relevance of Atofreellage.

Beneficial effects of rapamycin on endothelial function in systemic lupus erythematosus.

Introduction: Endothelial function is significantly impaired in patients with SLE compared to healthy controls. Elevated activation of the mammalian target of rapamycin complex 1 (mTORC1) is reported in humans and mice with SLE. However, it is unclear if elevated mTORC1 in SLE contributes to impaired mitophagy and endothelial dysfunction. Therefore, we tested the hypothesis that inhibiting mTORC1 with rapamycin would increase mitophagy and attenuate endothelial dysfunction and inflammatory responses in SLE. Methods: Nine-week-old female lupus-prone (MRL/lpr) and healthy control (MRL/MpJ) mice were randomly assigned into rapamycin treatment (lpr_Rapamycin and MpJ_Rapamycin) or control (lpr_Control and MpJ_Control) groups. Rapamycin was injected i.p. 3 days per week for 8 weeks. After 8 weeks, endothelium-dependent vasorelaxation to acetylcholine (ACh) and endothelium-independent vasorelaxation to sodium nitroprusside (SNP) were measured in thoracic aortas using a wire myograph. Results: MTORC1 activity was increased in aorta from lpr mice as demonstrated by increased phosphorylation of s6rp and p70s6k and significantly inhibited by rapamycin (s6rp, p < 0.0001, p70s6k, p = 0.04, respectively). Maximal responses to Ach were significantly impaired in lpr_Control (51.7% ± 6.6%) compared to MpJ_Control (86.7% ± 3.6%) (p < 0.0001). Rapamycin prevented endothelial dysfunction in the thoracic aorta from lupus mice (lpr_Rapamycin) (79.6% ± 4.2%) compared to lpr_Control (p = 0.002). Maximal responses to SNP were not different across groups. Phosphorylation of endothelial nitric oxide synthase also was 42% lower in lpr_Control than MpJ_Control and 46% higher in lpr_Rapamycin than lpr_Control. The inflammatory marker, vascular cell adhesion protein 1 (Vcam 1), was elevated in aorta from lupus mice compared with healthy mice (p = 0.001), and significantly reduced with Rapamycin treatment (p = 0.0021). Mitophagy markers were higher in lupus mice and reduced by rapamycin treatment, suggesting altered mitophagy in lpr mice. Conclusion: Collectively, these results demonstrate the beneficial effects of inhibiting mTORC1 on endothelial function in SLE mice and suggest inflammation and altered mitophagy contribute to endothelial dysfunction in SLE.

MYH11 rare variant augments aortic growth and induces cardiac hypertrophy and heart failure with pressure overload.

Smooth muscle cell-specific myosin heavy chain, encoded by MYH11, is selectively expressed in smooth muscle cells (SMCs). Pathogenic variants in MYH11 predispose to a number of disorders, including heritable thoracic aortic disease associated with patent ductus arteriosus, visceral myopathy, and megacystis-microcolon-intestinal hypoperistalsis syndrome. Rare variants of uncertain significance occur throughout the gene, including MYH11 p.Glu1892Asp, and we sought to determine if this variant causes thoracic aortic disease in mice. Genomic editing was used to generate Myh11 E1892D/E1892D mice. Wild-type (WT) and mutant mice underwent cardiovascular phenotyping and with transverse aortic constriction (TAC). Myh11 E1892D/E1892D and WT mice displayed similar growth, blood pressure, root and ascending aortic diameters, and cardiac function up to 13 months of age, along with similar contraction and relaxation on myographic testing. TAC induced hypertension similarly in Myh11 E1892D/E1892D and WT mice, but mutant mice showed augmented ascending aortic enlargement and increased elastic fragmentation on histology. Unexpectedly, male Myh11 E1892D/E1892D mice two weeks post-TAC had decreased ejection fraction, stroke volume, fractional shortening, and cardiac output compared to similarly treated male WT mice. Importantly, left ventricular mass increased significantly due to primarily posterior wall thickening, and cardiac histology confirmed cardiomyocyte hypertrophy and increased collagen deposition in the myocardium and surrounding arteries. These results further highlight the clinical heterogeneity associated with MYH11 rare variants. Given that MYH11 is selectively expressed in SMCs, these results implicate a role of vascular SMCs in the heart contributing to cardiac hypertrophy and failure with pressure overload.

Mapping the spatial distribution of primary and secondary PM2.5 in a multi-industrial city by combining monitoring and modeling results.

Industrial cities are strongly influenced by primary emissions of PM2.5 from local industries. In addition, gaseous precursors, such as sulfur oxides (SOX), nitrogen oxides (NOX), and volatile organic compounds (VOCs), emitted from industrial sources, undergo conversion into secondary inorganic and organic aerosols (SIAs and SOAs). In this study, the spatial distributions of primary and secondary PM2.5 in Ulsan, the largest industrial city in South Korea, were visualized. PM2.5 components (ions, carbons, and metals) and PM2.5 precursors (SO2, NO2, NH3, and VOCs) were measured to estimate the concentrations of secondary inorganic ions (SO42-, NO3-, and NH4+) and secondary organic aerosol formation potential (SOAFP). The spatial distributions of SIAs and SOAs were then plotted by combining atmospheric dispersion modeling, receptor modeling, and monitoring data. Spatial distribution maps of primary and secondary PM2.5 provide fundamental insights for formulating management policies in different districts of Ulsan. For instance, among the five districts in Ulsan, Nam-gu exhibited the highest levels of primary PM2.5 and secondary nitrate. Consequently, controlling both PM2.5 and NO2 emissions becomes essential in this district. The methodology developed in this study successfully identified areas with dominant contributions from both primary emissions and secondary formation. This approach can be further applied to prioritize control measures during periods of elevated PM levels in other industrial cities.

Genetic background influences arterial vasomotor function in male and female mice.

The purpose of this study was to assess the influence of genetic background and sex on nitric oxide (NO)-mediated vasomotor function in arteries from different vascular territories. Vasomotor function was assessed in thoracic aorta, abdominal aorta, carotid arteries, and femoral arteries from the following mouse strains: SJL/J, DBA/2J, NZW/LacJ, and C57BL/6J. Contractile responses were assessed using the α1-adrenergic receptor agonist phenylephrine (PE, 10-9 -10-5 M). Vasorelaxation responses were assessed by examining relaxation to an endothelium-dependent vasodilator acetylcholine (ACh, 10-9 -10-5 M) and an endothelium-independent vasodilator sodium nitroprusside (SNP, 10-9 -10-5 M). To evaluate the role of NO, relaxation responses to ACh and SNP were assessed in the absence or presence of a nitric oxide synthase inhibitor (N omega-nitro-l-arginine methyl ester hydrochloride: 10-4 M). Vasomotor responses to ACh and PE varied across strains and among the arteries tested with some strains exhibiting artery-specific impairment. Results indicated some concentration-response heterogeneity in response to ACh and SNP between vessels from females and males, but no significant differences in responses to PE. Collectively, these findings indicate that vasomotor responses vary by genetic background, sex, and artery type.

Nonlinear Associations between Blood Cadmium Concentration and Thyroid Hormones According to Smoking Status in Korean Adults: The Korea National Health and Nutrition Examination Survey (KNHANES).

Research on the association between blood cadmium (BCd) exposure and thyroid hormone levels in the general population has been inconclusive. Therefore, we examined the associations between BCd and thyroid hormones according to smoking status in Korean adults (N = 1170, Men = 722, Women = 448) using multiple linear regression and restricted cubic splines analysis with data from the Korean National Health and Nutrition Examination Survey (2013). The geometric mean of BCd was 0.74 µg/L in all study participants and was higher in smokers (1.01 µg/L) than in nonsmokers (0.65 µg/L). Restricted cubic splines analysis revealed nonlinear trends between BCd and free thyroxine in smokers (p for nonlinearity = 0.02). By contrast, there were no significant associations between BCd and thyroid hormones in either men or women. In conclusion, nonlinear associations may exist between BCd and free thyroxine in smokers. Our study provides empirical support for the future formulation of an acceptable concentration range of BCd and offers a new concept for preventing thyroid problems.

Effects of vitamin D on associations between air pollution and mental health outcomes in Korean adults: Results from the Korea National Health and Nutrition Examination Survey (KNHANES).

BACKGROUND: Evidence suggests that low individual vitamin D levels enhance adverse effects associated with air pollution on mental health conditions. The aim of this study was to identify associations between ambient air pollution exposure, mental health, and serum vitamin D status in the general population of South Korea. METHODS: We included national representative data for 29,373 adults in the final analysis. We measured serum 25-hydroxyvitamin D concentrations to assess vitamin D status for each participant. We assessed mental health factors (i.e., perceived stress, depressive symptoms, and suicidal ideation), and analyzed associations between these factors and individuals' annual average exposures to air pollutants, including particulate matter with an aerodynamic diameter ≤ 10 µm (PM10), nitrogen dioxide (NO2), sulfur dioxide, and carbon monoxide (CO). RESULTS: Using an adjusted model, we found PM10 affected mental health outcomes, such as perceived stress (odds ratio [OR] = 1.04; 95 % confidence interval [CI] = 1.00-1.09), depression symptoms (OR = 1.12; 95 % CI = 1.06-1.18), and suicidal ideation (OR = 1.11; 95 % CI = 1.05-1.17). Effects of the pollutants NO2 and CO were significant only in the group with perceived stress and depressive symptoms. PM10 and NO2 exposures were significantly associated with increased odds of adverse mental health in participants with vitamin D deficiency. LIMITATIONS: Since the cross-sectional design of KNHANES data, it is not possible to evaluate the causal relationship between air pollution exposure, vitamin D status and mental health. CONCLUSIONS: This study results suggest that associations between ambient air pollution and mental health outcomes were stronger in participants with vitamin D deficiency.

Chemical Constituents from the Roots of Angelica reflexa That Improve Glucose-Stimulated Insulin Secretion by Regulating Pancreatic ß-Cell Metabolism.

The aim of this study was to discover bioactive constituents of Angelica reflexa that improve glucose-stimulated insulin secretion (GSIS) in pancreatic ß-cells. Herein, three new compounds, namely, koseonolin A (1), koseonolin B (2), and isohydroxylomatin (3), along with 28 compounds (4-31) were isolated from the roots of A. reflexa by chromatographic methods. The chemical structures of new compounds (1-3) were elucidated through spectroscopic/spectrometric methods such as NMR and HRESIMS. In particular, the absolute configuration of the new compounds (1 and 3) was performed by electronic circular dichroism (ECD) studies. The effects of the root extract of A. reflexa (KH2E) and isolated compounds (1-31) on GSIS were detected by GSIS assay, ADP/ATP ratio assay, and Western blot assay. We observed that KH2E enhanced GSIS. Among the compounds 1-31, isohydroxylomatin (3), (-)-marmesin (17), and marmesinin (19) increased GSIS. In particular, marmesinin (19) was the most effective; this effect was superior to treatment with gliclazide. GSI values were: 13.21 ± 0.12 and 7.02 ± 0.32 for marmesinin (19) and gliclazide at a same concentration of 10 µM, respectively. Gliclazide is often performed in patients with type 2 diabetes (T2D). KH2E and marmesinin (19) enhanced the protein expressions associated with pancreatic ß-cell metabolism such as peroxisome proliferator-activated receptor γ, pancreatic and duodenal homeobox 1, and insulin receptor substrate-2. The effect of marmesinin (19) on GSIS was improved by an L-type Ca2+ channel agonist and K+ channel blocker and was inhibited by an L-type Ca2+ channel blocker and K+ channel activator. Marmesinin (19) may improve hyperglycemia by enhancing GSIS in pancreatic ß-cells. Thus, marmesinin (19) may have potential use in developing novel anti-T2D therapy. These findings promote the potential application of marmesinin (19) toward the management of hyperglycemia in T2D.

New Sesquiterpene Glycosides from the Flowers of Aster koraiensis and Their Inhibition Activities on EGF- and TPA-Induced Cell Transformation.

In total, four new eudesmane-type sesquiterpene glycosides, askoseosides A-D (1-4), and 18 known compounds (5-22) were isolated from the flowers of Aster koraiensis via chromatographic techniques. Chemical structures of the isolated compounds were identified by spectroscopic/spectrometric methods, including NMR and HRESIMS, and the absolute configuration of the new compounds (1 and 2) was performed by electronic circular dichroism (ECD) studies. Further, the anticancer activities of the isolated compounds (1-22) were evaluated using the epidermal growth factor (EGF)-induced as well as the 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced cell transformation assay. Among the 22 compounds, compounds 4, 9, 11, 13-15, 17, 18, and 22 significantly inhibited both EGF- and TPA-induced colony growth. In particular, askoseoside D (4, EGF: 57.8%; TPA: 67.1%), apigenin (9, EGF: 88.6%; TPA: 80.2%), apigenin-7-O-ß-d-glucuronopyranoside (14, EGF: 79.2%; TPA: 70.7%), and 1-(3',4'-dihydroxycinnamoyl) cyclopentane-2,3-diol (22, EGF: 60.0%; TPA: 72.1%) showed higher potent activities.

Accuracy of Impression Techniques for Dental Implants Placed in Five Different Orientations.

PURPOSE: The purpose of this study was to evaluate the impression accuracy of two implants placed in different orientations and compare the impression accuracy obtained with the dual-arch impression technique using hybrid impression copings and the conventional open-tray impression technique. MATERIALS AND METHODS: Five mandibular dentiform models were prepared by placing implants in the second premolar and second molar regions in the following different orientations: parallel to each other; 15-degree mesiodistal angulation; 30-degree mesiodistal angulation; 15-degree buccolingual angulation; and 30-degree buccolingual angulation. After making 10 impressions for each model with the open-tray impression technique and dual-arch impression technique with hybrid impression copings, cast models were fabricated for each impression (n = 10). Scan bodies were mounted on the five dentiform models and the fabricated 100 cast models were scanned using a desktop scanner. The three-dimensional deviation of the scan bodies on the cast models was calculated and compared to the reference data from the dentiform models. A two-way analysis of variance was conducted (α = .05). RESULTS: The root mean square deviation values obtained from the implants placed with 30-degree mesiodistal angulation were 93.05 ± 6.21 µm with the open-tray impression technique and 104.01 ± 8.89 µm with the dual-arch impression technique, which were the largest deviation values for both techniques (P < .001). Compared to the open-tray impression technique, the dual-arch impression technique with the hybrid impression copings showed significantly lower accuracy when the angulation between the implants was 15 degrees mesiodistally (P < .001), 30 degrees mesiodistally (P = .016), or 30 degrees buccolingually (P < .001). However, there was no significant difference between the accuracy of the two impression techniques for parallel implants (P = .74). CONCLUSION: When the two implants were inclined 30 degrees mesiodistally, both implant impression techniques showed the largest deviation and the dual-arch impression technique showed lower accuracy compared to the conventional open-tray impression technique. Parallel placement of implants may improve impression accuracy and enable use of the dual-arch impression technique.

Evaluation of Meibum Lipid Composition According to Tear Interferometric Patterns: RRH: Meibum Composition According to Interferometric Patterns.

PURPOSE: To determine the relationship between tear film interferometric patterns and properties of lipid, including rheological properties. DESIGN: Prospective, cross-sectional laboratory investigation. METHOD: This study included 105 subjects (94 dry eye patients and 11 normal participants). The subjects were divided into 3 categories (group 1, normal; group 2, thin; and group 3, irregular) according to interferometric patterns. According to tear interferometric patterns, ultra-performance liquid chromatography (LC) quadrupole-linear ion trap/mass spectrometry (MS)-based analysis was used to investigate lipid profiling of meibum. Rheological properties were examined by using a Langmuir-Blodgett trough with saline solution. RESULTS: Normal subjects showed Pearl-like patterns, and dry eye patients showed either irregular or thin patterns. Group 2 tended to be the evaporative type, and group 3 tended to be the aqueous-deficient type. Lipid profiling using LC-MS identified 280 lipid species of 25 lipid classes. In the meibum of the patient groups, the content of cholesteryl esters and nonpolar lipids was lower than that in the normal group. However, the content of polar lipids such as sphingolipids and phospholipids in the patient groups was higher than that in the normal group. Rheological properties showed that the lift-off areas were comparable among the 3 groups and the surface tension was the highest in group 1, followed by group 3 and group 2. CONCLUSIONS: The findings of this study suggest that tear interferometric patterns are associated with lipid profiling of meibum and its rheological properties. These results may contribute toward the development of new treatment modalities.

Systematic Review and Meta-Analysis of Endurance Exercise Training Protocols for Mice.

Inbred and genetically modified mice are frequently used to investigate the molecular mechanisms responsible for the beneficial adaptations to exercise training. However, published paradigms for exercise training in mice are variable, making comparisons across studies for training efficacy difficult. The purpose of this systematic review and meta-analysis was to characterize the diversity across published treadmill-based endurance exercise training protocols for mice and to identify training protocol parameters that moderate the adaptations to endurance exercise training in mice. Published studies were retrieved from PubMed and EMBASE and reviewed for the following inclusion criteria: inbred mice; inclusion of a sedentary group; and exercise training using a motorized treadmill. Fifty-eight articles met those inclusion criteria and also included a "classical" marker of training efficacy. Outcome measures included changes in exercise performance, V ˙ O2max, skeletal muscle oxidative enzyme activity, blood lactate levels, or exercise-induced cardiac hypertrophy. The majority of studies were conducted using male mice. Approximately 48% of studies included all information regarding exercise training protocol parameters. Meta-analysis was performed using 105 distinct training groups (i.e., EX-SED pairs). Exercise training had a significant effect on training outcomes, but with high heterogeneity (Hedges' g=1.70, 95% CI=1.47-1.94, Tau2=1.14, I2 =80.4%, prediction interval=-0.43-3.84). Heterogeneity was partially explained by subgroup differences in treadmill incline, training duration, exercise performance test type, and outcome variable. Subsequent analyses were performed on subsets of studies based on training outcome, exercise performance, or biochemical markers. Exercise training significantly improved performance outcomes (Hedges' g=1.85, 95% CI=1.55-2.15). Subgroup differences were observed for treadmill incline, training duration, and exercise performance test protocol on improvements in performance. Biochemical markers also changed significantly with training (Hedges' g=1.62, 95% CI=1.14-2.11). Subgroup differences were observed for strain, sex, exercise session time, and training duration. These results demonstrate there is a high degree of heterogeneity across exercise training studies in mice. Training duration had the most significant impact on training outcome. However, the magnitude of the effect of exercise training varies based on the marker used to assess training efficacy.

Crosstalk Between the Immune System and Plant-Derived Nanovesicles: A Study of Allergen Transporting.

Background: Nanometer-sized membrane-surrounded vesicles from different parts of plants including fruits are gaining increasing attention due to their anti-inflammatory and anticancer effects demonstrated by in vitro and in vivo studies, and as nanovectors for molecular delivery of exogenous substances. These nanomaterials are very complex and contain a diverse arsenal of bioactive molecules, such as nucleic acids, proteins, and lipids. Our knowledge about the transport of allergens in vesicles isolated from plant food is limited today. Methods: Here, to investigate the allergenicity of strawberry-derived microvesicles (MVs), nanovesicles (NVs), and subpopulations of NV, we have set up a multidisciplinary approach. The strategy combines proteomics-based protein identification, immunological investigations, bioinformatics, and data mining to gain biological insights useful to evaluate the presence of potential allergens and the immunoglobulin E (IgE) inhibitory activity of vesicle preparations. Results: Immunological test showed that several proteins of strawberry-derived vesicles compete for IgE binding with allergens spotted on the FABER biochip. This includes the known strawberry allergens Fra a 1, Fra a 3, and Fra a 4, and also other IgE-binding proteins not yet described as allergens in this food, such as gibberellin-regulated proteins, 2S albumin, pectate lyase, and trypsin inhibitors. Proteomics identified homologous sequences of the three strawberry allergens and their isoforms in total protein extract (TPE) but only Fra a 1 and Fra a 4 in the vesicle samples. Label-free quantitative proteomic analysis revealed no significant enrichment of these proteins in strawberry vesicles with respect to TPE. Conclusion: Immunological tests and bioinformatics analysis of proteomics data sets revealed that MVs and NVs isolated from strawberries can carry functional allergens their isoforms as well as proteins potentially allergenic based on their structural features. This should be considered when these new nanomaterials are used for human nutraceutical or biomedical applications.