ABSTRACT
Smooth muscle cell-specific myosin heavy chain, encoded by MYH11 , is selectively expressed in smooth muscle cells ( SMC s). 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. Author Summary: In this study, we explore the impact of a specific genetic variant, MYH11 p.Glu1892Asp, on the heart and blood vessels in mice. The MYH11 gene is crucial for smooth muscle cells, which are found in the walls of blood vessels and play an important role in various vascular diseases. We created mice with this genetic variant to see if it would lead to thoracic aortic disease, a condition affecting the main artery from the heart. We found that mice with the variant were similar to normal mice in many aspects, such as growth, blood pressure, and heart function, for up to 13 months. However, when we induced high blood pressure in the mice, the mutant mice showed more significant enlargement of the aorta and damage to the elastic fibers in the aortic walls. Interestingly, male mutant mice also developed heart problems, such as reduced heart pumping ability and increased heart muscle thickness, after the high blood pressure challenge. This was accompanied by signs of heart muscle cell enlargement and increased tissue stiffness. These findings suggest that this rare MYH11 variant can contribute to a range of heart and vascular issues, particularly under conditions of pressure overload, and highlight the importance of smooth muscle cells in the development of these problems.
ABSTRACT
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.
Subject(s)
Air Pollutants , Volatile Organic Compounds , Air Pollutants/analysis , Particulate Matter/analysis , Cities , Nitrogen Dioxide , Environmental Monitoring/methods , Nitrates , Volatile Organic Compounds/analysis , Aerosols/analysis , SeasonsABSTRACT
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.
Subject(s)
Acetylcholine , Vasodilator Agents , Mice , Male , Female , Animals , Mice, Inbred DBA , Mice, Inbred C57BL , Vasodilator Agents/pharmacology , Acetylcholine/pharmacology , Vasodilation/physiology , Femoral Artery/physiology , Nitric Oxide/pharmacology , NG-Nitroarginine Methyl Ester/pharmacology , Genetic Background , Endothelium, Vascular/physiologyABSTRACT
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.
Subject(s)
Overweight , Suicide, Attempted , Adolescent , Humans , Body Mass Index , Body Weight , Overweight/epidemiology , Thinness/epidemiology , Republic of Korea/epidemiology , Risk-Taking , Body ImageABSTRACT
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.
Subject(s)
Actins , Aortic Aneurysm, Thoracic , Mice , Animals , Actins/metabolism , Integrins/genetics , Integrins/metabolism , Myocytes, Smooth Muscle/metabolism , Aortic Aneurysm, Thoracic/metabolism , Cell-Matrix Junctions/metabolism , Muscle, Smooth/metabolismABSTRACT
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.
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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.
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Air Pollutants , Air Pollution , Vitamin D Deficiency , Humans , Adult , Nitrogen Dioxide/analysis , Nutrition Surveys , Cross-Sectional Studies , Air Pollutants/adverse effects , Air Pollutants/analysis , Particulate Matter/adverse effects , Particulate Matter/analysis , Vitamin D , Vitamins , Vitamin D Deficiency/epidemiology , Outcome Assessment, Health Care , Environmental Exposure/adverse effectsABSTRACT
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.
Subject(s)
Dental Implants , Dental Impression Technique , Dental Impression Materials , Models, DentalABSTRACT
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.
Subject(s)
Air Pollutants , Air Pollution , Vitamin D Deficiency , Adult , Air Pollutants/adverse effects , Air Pollutants/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Carbon Monoxide/analysis , Cross-Sectional Studies , Female , Humans , Male , Nitrogen Dioxide/analysis , Obesity/complications , Obesity/epidemiology , Particulate Matter/adverse effects , Particulate Matter/analysis , Vitamin D , Vitamins/analysisABSTRACT
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.
Subject(s)
Dry Eye Syndromes , Lacerations , Cross-Sectional Studies , Dry Eye Syndromes/diagnosis , Humans , Lipids , Meibomian Glands , Prospective Studies , Tears/chemistryABSTRACT
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.
ABSTRACT
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 Ë 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.
ABSTRACT
Periostin plays a crucial role in fibrosis, which is involved in kidney aging. A few studies have shown that lipid metabolism is involved in kidney aging. We investigated the role of periostin in lipid metabolism during kidney aging. Renal function, fibrosis, and inflammatory markers were studied using urine, blood, and tissue samples from wild-type (WT) C57BL/6 mice and Postn-null mice of 2 and 24 months of age. Lipids were quantitatively profiled using liquid chromatography-tandem mass spectrometry in the multiple reaction monitoring mode. Renal function was worse and tubular atrophy/interstitial fibrosis, periostin expression, and inflammatory and fibrotic markers were more severe in aged WT mice than in young WT mice. In aged Postn-null mice, these changes were mitigated. Thirty-five differentially regulated lipids were identified. Phosphatidylcholines, cholesteryl ester, cholesterol, ceramide-1-phosphate, and CCL5 expression were significantly higher in aged WT mice than in aged Postn-null mice. Particularly, linoleic acid, linolenic acid, arachidonic acid, and docosahexaenoic acid differed strongly between the two groups. Lysophosphatidylcholine acyltransferase 2, which converts lysophosphatidylcholine to phosphatidylcholine, was significantly higher in aged WT mice than in aged Postn-null mice. Periostin expression in the kidneys increased with age, and periostin ablation delayed aging. Changes in lipids and their metabolism were found in Postn-null mice. Further research on the precise mechanisms of and relationships between lipid expression and metabolism, kidney aging, and periostin expression is warranted.
Subject(s)
Aging/physiology , Cell Adhesion Molecules/metabolism , Kidney/pathology , Lipid Metabolism/genetics , Animals , Cell Adhesion Molecules/genetics , Gene Expression Regulation , Male , Mice , Mice, Knockout , Random AllocationABSTRACT
Aspilia africana has been used for generations to treat many diseases in Africa. Its biological activities, including antioxidant and anti-inflammatory potential, are attributed to a number of secondary metabolites, including alkaloids and polyphenolics. The antioxidant activities of A. africana callus (CA), juvenile in vitro leaf (IL) and root (IR), ex vitro root (SR) and leaf (SL), and wild leaf (WL) dried samples were assessed based on their diphenylpicrylhydrazyl (DPPH) free radical scavenging abilities. The total phenolic and flavonoid content of different plant samples was compared. Further, high-pressure liquid chromatography (HPLC) was used to quantitatively determine chlorogenic acid content in the A. africana plant samples. Fourier transform near-infrared (FT-NIR) analysis was also carried out to compare the antioxidant phytochemical content in the A. africana plant tissues. Among the samples, IR, with the highest total phenolic content (167.84 ± 1.057 mg GAE/g), total flavonoid content (135.06 ± 0.786 mg RUE/g), and chlorogenic acid (5.23 ± 0.298 mg/g) content, had the most potent antioxidant activity (IC50 = 27.25 ± 5.028 µg/mL), followed by WL. The lowest polyphenolic content and antioxidant activity were observed in SR. The antioxidant activities of A. africana tissues were positively correlated with the total phenolic and flavonoid content in the samples. The differences in antioxidant activities of A. africana tissues could be attributed to the difference in their polyphenolic content. Our study reports, for the first time, the antioxidant activities of A. africana callus and roots (in vitro and ex vitro). The A. africana samples IR, CA, and WL could be valuable natural sources of antioxidants that could be further exploited for the development of useful pharmaceutical products.
ABSTRACT
In contrast to nonalcoholic fatty liver disease (NAFLD), metabolic-associated fatty liver disease (MAFLD) as an innovative definition can coexist with significant alcohol consumption. Massive clinical observations have indicated that high-fat/-calorie diet induced metabolic dysfunction along with alcohol intake deteriorates steatotic liver injury. To explore the potential mechanisms of fatty diet together with alcohol-induced steatohepatitis, we adopted a rat model by comparing a half-dose combination of fat diet (20%) and alcohol (10%) with their corresponding double dose of 40% fat diet and 20% alcohol for 8 weeks. The notable alterations in histopathology, acceleration in the oxidation parameters (ROS, NO and lipid peroxidation) and serum transaminase levels were shown in the concomitant group. Concomitant use of a high-fat diet and alcohol provoked hepatic endoplasmic reticulum stress, but did not activate mitochondria-mediated apoptosis parameters compared to F. In contrast, the notable activation of caspase-12 and nuclear translocation of CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) were observed only in the combined treatment group. The concomitant dietary fat intake and alcohol consumption lead to liver injury initially and later to steatohepatitis by the overdose of fat or alcohol, and in which the CHOP and caspase-12 might be involved in synergistic acceleration of steatohepatitis through a mitochondria-independent manner.
ABSTRACT
Ginseng is a traditional herbal medicine in eastern Asian countries. Most active constituents in ginseng are prepared via fermentation or organic acid pretreatment. Extracellular vesicles (EVs) are released by most organisms from prokaryotes to eukaryotes and play central roles in intra- and inter-species communications. Plants produce EVs upon exposure to microbes; however, their direct functions and utility for human health are barely known, except for being proposed as delivery vehicles. In this study, we isolated EVs from ginseng roots (GrEVs) or the culture supernatants of ginseng cells (GcEVs) derived from Panax ginseng C.A. Meyer and investigated their biological effects on human skin cells. GrEV or GcEV treatments improved the replicative senescent or senescence-associated pigmented phenotypes of human dermal fibroblasts or ultraviolet B radiation-treated human melanocytes, respectively, by downregulating senescence-associated molecules and/or melanogenesis-related proteins. Based on comprehensive lipidomic analysis using liquid chromatography mass spectrometry, the lipidomic profile of GrEVs differed from that of the parental root extracts, showing significant increases in 70 of 188 identified lipid species and prominent increases in diacylglycerols, some phospholipids (phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine), and sphingomyelin, revealing their unique vesicular properties. Therefore, our results imply that GEVs represent a novel type of bioactive and sustainable nanomaterials that can be applied to human tissues for improving tissue conditions and targeted delivery of active constituents.
Subject(s)
Chromatography, High Pressure Liquid/methods , Extracellular Vesicles/drug effects , Mass Spectrometry/methods , Panax/chemistry , Plants, Medicinal/chemistry , Skin/drug effects , Cell Proliferation , HumansABSTRACT
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.
Subject(s)
Biomarkers, Tumor/metabolism , Extracellular Vesicles/metabolism , Leukemia, Myeloid, Acute/metabolism , Adolescent , Adult , Aged , Antigens, CD/genetics , Antigens, CD/metabolism , Cells, Cultured , Female , Humans , Male , Middle Aged , Protein Kinases/metabolism , Proteomics , Young AdultABSTRACT
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.