Angelica gigas extract inhibits acetylation of eNOS via IRE1α sulfonation/RIDD-SIRT1-mediated posttranslational modification in vascular dysfunction.

Angelica gigas NAKAI (AG) is a popular traditional medicinal herb widely used to treat dyslipidemia owing to its antioxidant activity. Vascular disease is intimately linked to obesity-induced metabolic syndrome, and AG extract (AGE) shows beneficial effects on obesity-associated vascular dysfunction. However, the effectiveness of AGE against obesity and its underlying mechanisms have not yet been extensively investigated. In this study, 40 high fat diet (HFD) rats were supplemented with 100-300 mg/kg/day of AGE to determine its efficacy in regulating vascular dysfunction. The vascular relaxation responses to acetylcholine were impaired in HFD rats, while the administration of AGE restored the diminished relaxation pattern. Endothelial dysfunction, including increased plaque area, accumulated reactive oxygen species, and decreased nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) Ser1177 phosphorylation, were observed in HFD rats, whereas AGE reversed endothelial dysfunction and its associated biochemical signaling. Furthermore, AGE regulated endoplasmic reticulum (ER) stress and IRE1α sulfonation and its subsequent sirt1 RNA decay through controlling regulated IRE1α-dependent decay (RIDD) signaling, ultimately promoting NO bioavailability via the SIRT1-eNOS axis in aorta and endothelial cells. Independently, AGE enhanced AMPK phosphorylation, additionally stimulating SIRT1 and eNOS deacetylation and its associated NO bioavailability. Decursin, a prominent constituent of AGE, exhibited a similar effect in alleviating endothelial dysfunctions. These data suggest that AGE regulates dyslipidemia-associated vascular dysfunction by controlling ROS-associated ER stress responses, especially IRE1α-RIDD/sirt1 decay and the AMPK-SIRT1 axis.

Integration of Single-Cell RNA-Seq Datasets: A Review of Computational Methods.

With the increased number of single-cell RNA sequencing (scRNA-seq) datasets in public repositories, integrative analysis of multiple scRNA-seq datasets has become commonplace. Batch effects among different datasets are inevitable because of differences in cell isolation and handling protocols, library preparation technology, and sequencing platforms. To remove these batch effects for effective integration of multiple scRNA-seq datasets, a number of methodologies have been developed based on diverse concepts and approaches. These methods have proven useful for examining whether cellular features, such as cell subpopulations and marker genes, identified from a certain dataset, are consistently present, or whether their condition-dependent variations, such as increases in cell subpopulations in particular disease-related conditions, are consistently observed in different datasets generated under similar or distinct conditions. In this review, we summarize the concepts and approaches of the integration methods and their pros and cons as has been reported in previous literature.

Efficacy and Safety of Sesame Oil Cake Extract on Memory Function Improvement: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Pilot Study.

The goal of treatment for mild cognitive impairment (MCI) is to reduce the existing clinical symptoms, delay the progression of cognitive impairment and prevent the progression to Alzheimer's disease (AD). At present, there is no effective drug therapy for AD treatment. However, early intake of dietary supplements may be effective in alleviating and delaying the MCI. This study aims to evaluate the effects of sesame oil cake extract (SOCE) supplementation on cognitive function in aged 60 years or older adults with memory impairment. A total of 70 subjects received either SOCE (n = 35) or placebo (n = 35) for 12 weeks based on random 1:1 assignment to these two groups. Cognitive function was evaluated by a computerized neurocognitive function test (CNT), and changes in the concentrations of plasma amyloid ß (Aß) proteins and urine 8-OHdG (8-hydroxy-2'-deoxyguanosine) were investigated before and after the experiment. Verbal learning test index items of the CNT improved markedly in the SOCE group compared to the placebo group (p < 0.05). Furthermore, plasma amyloid-ß (1-40) and amyloid-ß (1-42) levels in the SOCE group decreased significantly compared to that in the placebo group (p < 0.05). There was no statistically significant difference in urine 8-OHdG between the two groups (p > 0.05). Collectively, intake of SOCE for 12 weeks appears to have a beneficial effect on the verbal memory abilities and plasma ß-amyloid levels of older adults with memory impairment.

Pectin-Lyase-Modified Ginseng Extract and Ginsenoside Rd Inhibits High Glucose-Induced ROS Production in Mesangial Cells and Prevents Renal Dysfunction in db/db Mice.

Diabetes increases the incidence rate of chronic renal disease. Pectin-lyase-modified ginseng (GS-E3D), with enhanced ginsenoside Rd content, has been newly developed. In this study, renal protective roles of GS-E3D in type-2 diabetic db/db mice were investigated. The generation of reactive oxygen species (ROS) induced by high glucose (25 mM) was reduced by ES-E3D (75%) and ginsenoside Rd (60%). Diabetic db/db mice received 100 or 250 mg/kg/day of GS-E3D daily via oral gavage for 6 weeks. Albuminuria and urinary 8-hydroxy-2'-deoxyguanosine (8-OhdG, an oxidative stress marker) levels were increased in db/db mice and the levels recovered after GS-E3D treatment. In renal tissues, TUNEL-positive cells were decreased after GS-E3D treatment, and the increased apoptosis-related protein expressions were restored after GS-E3D treatment. Therefore, GS-E3D has a potent protective role in diabetes-induced renal dysfunction through antioxidative and antiapoptotic activities. These results may help patients to select a dietary supplement for diabetes when experiencing renal dysfunction.

Anthocyanins attenuate endothelial dysfunction through regulation of uncoupling of nitric oxide synthase in aged rats.

Endothelial dysfunction is one of the main age-related arterial phenotypes responsible for cardiovascular disease (CVD) in older adults. This endothelial dysfunction results from decreased bioavailability of nitric oxide (NO) arising downstream of endothelial oxidative stress. In this study, we investigated the protective effect of anthocyanins and the underlying mechanism in rat thoracic aorta and human vascular endothelial cells in aging models. In vitro, cyanidin-3-rutinoside (C-3-R) and cyanidin-3-glucoside (C-3-G) inhibited the d-galactose (d-gal)-induced senescence in human endothelial cells, as indicated by reduced senescence-associated-ß-galactosidase activity, p21, and p16INK4a . Anthocyanins blocked d-gal-induced reactive oxygen species (ROS) formation and NADPH oxidase activity. Anthocyanins reversed d-gal-mediated inhibition of endothelial nitric oxide synthase (eNOS) serine phosphorylation and SIRT1 expression, recovering NO level in endothelial cells. Also, SIRT1-mediated eNOS deacetylation was shown to be involved in anthocyanin-enhanced eNOS activity. In vivo, anthocyanin-rich mulberry extract was administered to aging rats for 8 weeks. In vivo, mulberry extract alleviated endothelial senescence and oxidative stress in the aorta of aging rats. Consistently, mulberry extract also raised serum NO levels, increased phosphorylation of eNOS, increased SIRT1 expression, and reduced nitrotyrosine in aortas. The eNOS acetylation was higher in the aging group and was restored by mulberry extract treatment. Similarly, SIRT1 level associated with eNOS decreased in the aging group and was restored in aging plus mulberry group. These findings indicate that anthocyanins protect against endothelial senescence through enhanced NO bioavailability by regulating ROS formation and reducing eNOS uncoupling.

Effects of a Lifestyle-Modification Program on Blood-Glucose Regulation and Health Promotion in Diabetic Patients: A Randomized Controlled Trial.

BACKGROUND: We aimed to investigate the efficacy of the lifestyle intervention (LSI) program in controlling blood glucose regulation and health promotion in type 2 diabetic (T2D) patients. METHODS: Thirty adults with a diagnosed with diabetes were randomly assigned to LSI and control groups. The LSI group maintained their daily routines after participating twice in the LSI program, while control group maintained 4 weeks of daily life without participating in an intervention. RESULTS: HbA1c levels in the LSI group decreased significantly after participation (p = 0.025) compared with levels before the study, but there was no significant difference between the groups. The weight and body mass index (BMI) of the LSI group tended to decrease significantly compared with the control group (p = 0.054 and p = 0.055, respectively), and the waist circumference (WC) of the LSI group decreased significantly compared with that of the control group (p = 0.048). In the effects of the LSI program according to the polymorphism of GCKR genes, changes in glycated albumin (GA) (%), HbA1c, WC, BMI, and weight showed a significant decrease in the non-risk (TT genotype) GCKR group compared with the risk group (CC and TC genotype). CONCLUSION: Application of the four-week LSI program to diabetics revealed positive effects on blood-glucose control and improvement in obesity indicators. In particular, the risk group with variations in the GCKR gene was associated with more genetic effects on indicators such as blood glucose and obesity than was the non-risk group.

Aucuba japonica extract inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy, with its bioactive components preventing VEGF-induced retinal vascular hyperpermeability.

Neovascularization in the retina is common pathophysiology of diabetic retinal microvasculopathy and exudative macular degeneration. Our study assessed the inhibitory activity of an ethanol-based extract of Aucuba japonica (AJE) on abnormal angiogenesis in the retina with a hyperoxia-induced neovascular retinopathy model. The inhibitory effects of aucubin, quercetin, and kaempferol, bioactive compounds, from A. japonica, on retinal vascular hyperpermeability were also examined. On the 7th postnatal day (P7), the C57BL/6 pups were exposed to a hyperoxic environment with 75% oxygen to develop the experimental angiogenesis in retinas. On the 12th postnatal day (P12), the pups were then returned to the normal atmospheric pressure of oxygen. From P12 to P16, the administration was intraperitoneal. The dose per day was 250 mg per kg weight. Retinal neovascularization was measured with retinal flat mounts prepared on P17. We also measured the vascular leakage mediated by the vascular endothelial growth factor (VEGF) in retinas. Mice treated with AJE had markedly smaller neovascular lesions, in comparison with vehicle-administered mice. AJE downregulated the expression of both VEGF protein and mRNA. In addition, aucubin, quercetin, and kaempferol ameliorated VEGF-induced retinal vascular leakage. The results of our study suggest that AJE is a potent antiangiogenic substance. AJE could also serve as a therapeutic agent for abnormal growth of vessels in the retina in patients with ischemic retinopathy. The bioactive compounds of AJE may be responsible for its antiangiogenic abilities.

Effects of Porphyra tenera Supplementation on the Immune System: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial.

OBJECTIVE: The purpose of this study was to determine if Porphyra tenera extract (PTE) has immune-enhancing effects and is safe in healthy adults. METHODS: Subjects who met the inclusion criteria (3 × 103 ≤ peripheral blood leukocyte level ≥ 8 × 103 cells/µL) were recruited for this study. Enrolled subjects (n = 120) were randomly assigned to either the PTE group (n = 60) and were given 2.5 g/day of PTE (as PTE) in capsule form or the placebo group (n = 60) and were given crystal cellulose capsules with the identical appearance, weight, and flavor as the PTE capsules for 8 weeks. Outcomes were assessed based on measuring natural killer (NK) cell activity, cytokines level, and upper respiratory infection (URI), and safety parameters were assessed at baseline and 8 weeks. RESULTS: Compared with baseline, NK cell activity (%) increased for all effector cell-to-target cell ratios in the PTE group after 8 weeks; however, changes were not observed in the placebo group (p < 0.10). Subgroup analysis of 101 subjects without URI showed that NK cell activity in the PTE group tended to increase for all effector cell/target cell (E:T) ratios (E:T = 12.5:1 p = 0.068; E:T = 25:1 p = 0.036; E:T = 50:1 p = 0.081) compared with the placebo group. A significant difference between the two groups was observed for the E:T = 25:1 ratio, which increased from 20.3 ± 12.0% at baseline to 23.2 ± 12.4% after 8 weeks in the PTE group (p = 0.036). A significant difference was not observed in cytokine between the two groups. CONCLUSION: PTE supplementation appears to enhance immune function by improving NK cell activity without adverse effects in healthy adults.

The Validity of the YMCA 3-Minute Step Test for Estimating Maximal Oxygen Uptake in Healthy Korean and Vietnamese Adults.

BACKGROUND: Cardiorespiratory fitness (CRF) is a fundamental component of physical fitness. While maximal oxygen uptake (VO2max) is the gold standard for quantifying CRF, standard maximal exercise tests using direct measurements VO2max are dependent on the availability of laboratory equipment, and thereby expensive and time consuming. Recently, an equation was formulated to indirectly estimate VO2max using the YMCA 3-minute step test. METHODS: The study included 15 Korean (KR) and 15 Vietnamese (VN) healthy adults aged 19-35 years. All subjects completed a YMCA 3-minute step test (YMCA 3MST) and a maximal exercise treadmill test to predict VO2max and VO2max measures, respectively. RESULTS: There was a significant relationship between VO2max predicted from the YMCA 3MST and actual VO2max measurements from the treadmill test (r = 0.80, p < 0.0001; KR group: r = 0.81, p < 0.0001; VN group: r = 0.93, p < 0.0001). Bland-Altman analysis revealed statistical agreement between tests, although there was a systematic overestimation of 3.36 mL/kg/min for the KR group. CONCLUSION: The equation for predicting VO2max from the YMCA 3MST was validated among the study subjects. However, future research should explore the validity and reliability of the YMCA 3MST equation for estimating VO2max in other populations.

Serum Follicle-Stimulating Hormone Levels Are Associated with Cardiometabolic Risk Factors in Post-Menopausal Korean Women.

: Menopause compounds many cardiometabolic risk factors through endogenous estrogen withdrawal. This study aimed to find the association between serum follicle-stimulating hormone (FSH) levels and cardiometabolic risk factors in post-menopausal Korean women. A total of 608 post-menopausal women from eight randomized double-blind, placebo-controlled clinical trials on menopause during the year 2012-2019 were analyzed. Cardiometabolic risk factors such as body mass index, waist circumference, systolic blood pressure, fasting glucose, triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), and TG/HDL-C ratio were significantly improved as the FSH quartiles increased. Metabolic syndrome (MetS) and the number of components of MetS decreased as FSH quartiles increased. In regression analysis, FSH level was negatively associated with cardiometabolic risk factors including body mass index, body weight, waist circumference, fasting glucose and TG, while it was positively associated with HDL-C. The odds ratio of MetS in the first quartile of FSH was 2.682 compared with that in the fourth quartile of FSH in a logistic regression model. Serum FSH levels had a negative correlation with cardiometabolic risk factors in post-menopausal Korean women, suggesting that a low FSH can be a predictor for cardiovascular disease in post-menopausal women.

A Lightweight Deep Learning Model for Fast Electrocardiographic Beats Classification With a Wearable Cardiac Monitor: Development and Validation Study.

BACKGROUND: Electrocardiographic (ECG) monitors have been widely used for diagnosing cardiac arrhythmias for decades. However, accurate analysis of ECG signals is difficult and time-consuming work because large amounts of beats need to be inspected. In order to enhance ECG beat classification, machine learning and deep learning methods have been studied. However, existing studies have limitations in model rigidity, model complexity, and inference speed. OBJECTIVE: To classify ECG beats effectively and efficiently, we propose a baseline model with recurrent neural networks (RNNs). Furthermore, we also propose a lightweight model with fused RNN for speeding up the prediction time on central processing units (CPUs). METHODS: We used 48 ECGs from the MIT-BIH (Massachusetts Institute of Technology-Beth Israel Hospital) Arrhythmia Database, and 76 ECGs were collected with S-Patch devices developed by Samsung SDS. We developed both baseline and lightweight models on the MXNet framework. We trained both models on graphics processing units and measured both models' inference times on CPUs. RESULTS: Our models achieved overall beat classification accuracies of 99.72% for the baseline model with RNN and 99.80% for the lightweight model with fused RNN. Moreover, our lightweight model reduced the inference time on CPUs without any loss of accuracy. The inference time for the lightweight model for 24-hour ECGs was 3 minutes, which is 5 times faster than the baseline model. CONCLUSIONS: Both our baseline and lightweight models achieved cardiologist-level accuracies. Furthermore, our lightweight model is competitive on CPU-based wearable hardware.

Anti-angiogenic effect of EGHB010, a standardized herbal formula of Paeoniae radix and Glycyrrhizae radix.

EGHB010 is a standardized herbal formula of the rhizome mixture of Paeonia lactiflora Pallas and Glycyrrhiza uralensis Fisch. Neovascularization in the retina is a common pathophysiology of diabetic retinal microvasculopathy and exudative macular degeneration. In this study, we evaluated the inhibitory effects of EGHB010 on abnormal retinal angiogenesis in a hyperoxia-induced neovascular retinopathy model. Vascular endothelial growth factor (VEGF)-mediated vascular tube formation was assayed in human umbilical vascular endothelial cells (HUVECs). Experimental angiogenesis in the retinas was induced by exposing C57BL/6 pups to hyperoxic environment (75% oxygen) on postnatal day 7 (P7) and then returning them to normal oxygen pressure on P12. EGHB010 (50 and 100 mg/kg/day) was administered intraperitoneally for 5 days (P12 - P16). Retinal flat mounts were prepared to measure the extent of retinal neovascularization on P17. The incubation of HUVECs with EGHB010 (1-25 µg/mL) resulted in the inhibition of VEGF-mediated tube formation in a dose-dependent manner. EGHB010 at doses of 50 and 100 mg/kg/day inhibited the formation of retinal neovascular tufts by 31.15±2.28% and 59.83±2.92%, respectively. Together, our results indicate that EGHB010 is a potent anti-angiogenic agent and may have potential for the control of abnormal retinal vessel growth in patients with ischemic retinopathy.

Biosignal-Based Attention Monitoring to Support Nuclear Operator Safety-Relevant Tasks.

In the main control room (MCR) of a nuclear power plant (NPP), the quality of an operator's performance can depend on their level of attention to the task. Insufficient operator attention accounted for more than 26% of the total causes of human errors and is the highest category for errors. It is therefore necessary to check whether operators are sufficiently attentive either as supervisors or peers during reactor operation. Recently, digital control technologies have been introduced to the operating environment of an NPP MCR. These upgrades are expected to enhance plant and operator performance. At the same time, because personal computers are used in the advanced MCR, the operators perform more cognitive works than physical work. However, operators may not consciously check fellow operators' attention in this environment indicating potentially higher importance of the role of operator attention. Therefore, remote measurement of an operator's attention in real time would be a useful tool, providing feedback to supervisors. The objective of this study is to investigate the development of quantitative indicators that can identify an operator's attention, to diagnose or detect a lack of operator attention thus preventing potential human errors in advanced MCRs. To establish a robust baseline of operator attention, this study used two of the widely used biosignals: electroencephalography (EEG) and eye movement. We designed an experiment to collect EEG and eye movements of the subjects who were monitoring and diagnosing nuclear operator safety-relevant tasks. There was a statistically significant difference between biosignals with and without appropriate attention. Furthermore, an average classification accuracy of about 90% was obtained by the k-nearest neighbors and support vector machine classifiers with a few EEG and eye movements features. Potential applications of EEG and eye movement measures in monitoring and diagnosis tasks in an NPP MCR are also discussed.

Aucubin, An Active Ingredient in Aucuba japonica, Prevents N-methyl-N-nitrosourea-induced Retinal Degeneration in Mice.

In the present study, we examined the potent retinoprotective effects of an ethanol-based extract of Aucuba japonica (AJE) and its active ingredient, aucubin, on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration in mice. Retinal degeneration was induced by an intraperitoneal injection of MNU (60 mg/kg). AJE (250 mg/kg) and aucubin (15 mg/kg) were orally administered for 1 week after the MNU injection. Electroretinography (ERG) and histological examinations were performed. Retinal apoptosis and oxidative DNA damage were also quantified. The retinoprotective abilities of AJE and aucubin were also assessed in primary cultured retinal cells. Morphologically, MNU induced a remarkable decrease in the outer nuclear layer, which contains photoreceptor cells. However, this layer was well preserved in the AJE- and aucubin-administered mice. The ERG responses significantly decreased in both a- and b-wave amplitudes in the MNU-injected mice. In the AJE and aucubin-treated mice, ERG responses were significantly increased. In addition, a terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay and immunohistochemical staining for 8-hydroxydeoxyguanosine (8-OHdG) revealed that both AJE and aucubin attenuated MNU-induced photoreceptor cell apoptosis and oxidative DNA damage. Furthermore, the in vitro assay also showed that AJE and aucubin have potent anti-oxidative and anti-apoptotic activities in primary cultured retinal cells. These results indicate that AJE and aucubin have potent retinoprotective effects, and that this retinoprotective activity is as a result of the potency of the bioactive compound, aucubin. These pharmacological characteristics suggest the additional application of AJE or aucubin in the treatment of patients with retinal degenerative diseases.

Ethyl Pyruvate Prevents Renal Damage Induced by Methylglyoxal-Derived Advanced Glycation End Products.

The renal accumulation of advanced glycation end products (AGEs) is a causative factor of various renal diseases, including chronic kidney disease and diabetic nephropathy. AGE inhibitors, such as aminoguanidine and pyridoxamine, have the therapeutic activities for reversing the increase in renal AGE burden. This study evaluated the inhibitory effects of ethyl pyruvate (EP) on methylglyoxal- (MGO-) modified AGE cross-links with proteins in vitro. We also determined the potential activity of EP in reducing the renal AGE burden in exogenously MGO-injected rats. EP inhibited MGO-modified AGE-bovine serum albumin (BSA) cross-links to collagen (IC50 = 0.19 ± 0.03 mM) in a dose-dependent manner, and its activity was stronger than aminoguanidine (IC50 = 35.97 ± 0.85 mM). In addition, EP directly trapped MGO (IC50 = 4.41 ± 0.08 mM) in vitro. In exogenous MGO-injected rats, EP suppressed AGE burden and MGO-induced oxidative injury in renal tissues. These activities of EP on the MGO-mediated AGEs cross-links with protein in vitro and in vivo showed its pharmacological potential for inhibiting AGE-induced renal diseases.

Antiglycation Activity of Aucubin In Vitro and in Exogenous Methylglyoxal Injected Rats.

Advanced glycation end products (AGEs) is a causative factor of various chronic diseases, including chronic kidney disease and atherosclerosis. AGE inhibitors, such as aminoguanidine and pyridoxamine, have the therapeutic activities for reversing the increase in AGEs burden. This study evaluated the inhibitory effects of aucubin on the formation of methylglyoxal (MGO)-modified AGEs in vitro. We also determined the potential activity of aucubin in reducing the AGEs burden in the kidney, blood vessel, heart, and retina of exogenously MGO-injected rats. Aucubin inhibited the formation of MGO-modified AGE-bovine serum albumin (IC50 = 0.57 ± 0.04 mmol/L) and its cross-links to collagen (IC50 = 0.55 ± 0.02 mmol/L) in a dose-dependent manner. In addition, aucubin directly trapped MGO (IC50 = 0.22 ± 0.01 mmol/L) in vitro. In exogenous MGO-injected rats, aucubin suppressed the formation of circulating AGEs and its accumulation in various tissues. These activities of aucubin on the MGO-derived AGEs in vitro and in vivo showed its pharmacological potential for inhibiting AGEs-related various chronic diseases.

Neural Correlates of Variations in Human Trust in Human-like Machines during Non-reciprocal Interactions.

As intelligent machines have become widespread in various applications, it has become increasingly important to operate them efficiently. Monitoring human operators' trust is required for productive interactions between humans and machines. However, neurocognitive understanding of human trust in machines is limited. In this study, we analysed human behaviours and electroencephalograms (EEGs) obtained during non-reciprocal human-machine interactions. Human subjects supervised their partner agents by monitoring and intervening in the agents' actions in this non-reciprocal interaction, which reflected practical uses of autonomous or smart systems. Furthermore, we diversified the agents with external and internal human-like factors to understand the influence of anthropomorphism of machine agents. Agents' internal human-likenesses were manifested in the way they conducted a task and affected subjects' trust levels. From EEG analysis, we could define brain responses correlated with increase and decrease of trust. The effects of trust variations on brain responses were more pronounced with agents who were externally closer to humans and who elicited greater trust from the subjects. This research provides a theoretical basis for modelling human neural activities indicate trust in partner machines and can thereby contribute to the design of machines to promote efficient interactions with humans.

Mulberry Extract Attenuates Endothelial Dysfunction through the Regulation of Uncoupling Endothelial Nitric Oxide Synthase in High Fat Diet Rats.

Dyslipidemia is associated with endothelial dysfunction, which is linked to nitric oxide (NO) biology. The coupling of endothelial NO synthase with cofactors is a major step for NO release. This study is aimed to investigate the vascular pharmacology effects of mulberry in rat thoracic aorta and human vascular endothelial cells. In vitro, we investigated the protective effects of the mulberry extract and its main component cyanidin-3-rutinoside (C-3-R), against oxidized low-density lipoprotein (ox-LDL)-induced endothelial nitric oxide synthase (eNOS) uncoupling. Whereas ox-LDL significantly decreased NO levels in endothelial cells, mulberry extract, and C-3-R significantly recovered NO levels and phospho-eNOS Thr495 and Ser1177 expression. In vivo, mulberry was administered to 60% of high-fat diet (w/w)-fed Sprague Dawley (SD) rats for six weeks, in which endothelium-dependent relaxations were significantly improved in organ bath studies and isometric tension recordings. Consistently, aortic expressions of phospho-eNOS and nitrotyrosine were increased. Mulberry also raised serum NO levels, increased phosphorylation of eNOS, and reduced nitrotyrosine and intracellular reactive oxygen species (ROS) in aortas, showing that mulberry preserves endothelium-dependent relaxation in aortas from high-fat diet rats. We suggest that this effect is mediated through enhanced NO bioavailability, in which the regulation of ROS and its reduced eNOS uncoupling are involved.

Immunomodulatory effects of a mycelium extract of Cordyceps (Paecilomyces hepiali; CBG-CS-2): a randomized and double-blind clinical trial.

BACKGROUND: Cordyceps is a traditional Chinese herb that produces various biopharmaceutical effects, including immune-enhancing effects. In this study, we prepared a Cordyceps mycelium culture extract (Paecilomyces hepiali, CBG-CS-2) to confirm its efficacy in enhancing the immune system and to evaluate its safety in healthy adults. METHODS: Healthy adults were divided into the intervention group (n = 39), who were given 1.68 g/day of CBG-CS-2 in capsules, and the control group (n = 40) for 8 weeks. The activities of natural killer (NK) cells and serum levels of monocyte-derived mediators were assessed initially for a baseline measurement and after 8 wks. RESULTS: The CBG-CS-2 group showed a significant 38.8 ± 17.6% enhancement from the baseline of NK cell cytotoxic activity relative to the placebo group after the administration of the capsules for 8 wks. (P < 0.019). CONCLUSION: The results suggest that the immune system functions well with CBG-CS-2 supplementation, perhaps with less accompanying inflammation. Thus, CBG-CS-2 is safe and effective for enhancing cell-mediated immunity in healthy adults. TRIAL REGISTRATION: This study was registered at Clinical Trials.gov ( NCT 02814617 ).

Ginseng Extract Modified by Pectin Lyase Inhibits Retinal Vascular Injury and Blood-Retinal Barrier Breakage in a Rat Model of Diabetes.

GS-E3D is an enzymatically modified ginseng extract by pectin lyase. In this study, we evaluated the preventive effects of GS-E3D on blood-retinal barrier (BRB) leakage in a rat model of diabetes. To produce diabetes, rats were injected with streptozotocin. GS-E3D was orally gavaged at 25, 50, and 100 mg/kg body weight for 6 weeks. We then compared the effect of GS-E3D with that of an unmodified ginseng extract (UGE) on retinal vascular leakage. The administration of GS-E3D significantly blocked diabetes-induced BRB breakdown. Immunofluorescence staining showed that GS-E3D reduced the loss of occludin in diabetic rats. In TUNEL staining, the number of apoptotic retinal microvascular cells was dose dependently decreased by GS-E3D treatment. GS-E3D decreased the accumulations of advanced glycation end products in the retinal vessels. In addition, the inhibition potential of GS-E3D on BRB breakage was stronger compared with UGE. These results indicate that GS-E3D could be a beneficial treatment option for preventing diabetes-induced retinal vascular injury.