Lactiplantibacillusplantarum ATG-K2 Exerts an Anti-Obesity Effect in High-Fat Diet-Induced Obese Mice by Modulating the Gut Microbiome.

Obesity is a major health problem. Compelling evidence supports the beneficial effects of probiotics on obesity. However, the anti-obesity effect of probiotics remains unknown. In this study, we investigated the anti-obesity effects and potential mechanisms of Lactiplantibacillus plantarum ATG-K2 using 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese mice. 3T3-L1 cells were incubated to determine the effect of lipid accumulation with lysate of L. plantarum ATG-K2. Mice were fed a normal fat diet or HFD with L. plantarum ATG-K2 and Orlistat for 8 weeks. L. plantarum ATG-K2 inhibited lipid accumulation in 3T3-L1 adipocytes, and reduced body weight gain, WAT weight, and adipocyte size in HFD-induced obese mice, concurrently with the downregulation of PPARγ, SREBP1c, and FAS and upregulation of PPARα, CTP1, UCP1, Prdm16, and ND5. Moreover, L. plantarum ATG-K2 decreased TG, T-CHO, leptin, and TNF-α levels in the serum, with corresponding gene expression levels in the intestine. L. plantarum ATG-K2 modulated the gut microbiome by increasing the abundance of the Lactobacillaceae family, which increased SCFA levels and branched SCFAs in the feces. L. plantarum ATG-K2 exhibited an anti-obesity effect and anti-hyperlipidemic effect in 3T3-L1 adipocytes and HFD-induced obese mice by alleviating the inflammatory response and regulating lipid metabolism, which may be influenced by modulation of the gut microbiome and its metabolites. Therefore, L. plantarum ATG-K2 can be a preventive and therapeutic agent for obesity.

The effect of knee joint rotation in the sagittal and axial plane on the measurement accuracy of coronal alignment of the lower limb.

BACKGROUND: Although the measurement of coronal alignment of the lower limb on conventional full-length weight-bearing anteroposterior (FLWAP) radiographs was reported to be influenced by the knee joint rotation, no comparative analysis was performed considering the effects of knee joint rotation on the sagittal and axial planes simultaneously using the three-dimensional images while taking into account the actual weight-bearing conditions. The aim of this study was to investigate the effect of knee joint rotation on the measurement accuracy of coronal alignment of the lower limb on the FLWAP radiograph. METHODS: Radiographic images of 90 consecutive patients (180 lower limbs) who took both the FLWAP radiograph and the EOS image were retrospectively reviewed. The relationship among delta values of mechanical tibiofemoral angle (mTFA) between the FLWAP radiographs and the EOS images (ΔmTFA), knee flexion/extension angle (sagittal plane rotation) on the EOS images, and patellar rotation (axial plane rotation) on the FLWAP radiographs were analyzed. Further, subgroup analysis according to each direction of knee joint rotation was performed. RESULTS: There was a significant correlation between ΔmTFA and sagittal plane rotation (r = 0.368, P <  0.001), whereas axial plane rotation was not correlated. In the analysis according to the direction, statistically significant correlation was observed only in the knee flexion group (r = 0.399, P <  0.001). The regression analysis showed a significant linear relationship between ΔmTFA and sagittal plane rotation (r2 = 0.136, P <  0.001). Additional subgroup analysis in patients with the patellar rotation greater than 3% showed a similar result of a linear relationship between ΔmTFA and sagittal plane rotation (r2 = 0.257, P <  0.001), whereas no statistically significant relationship was found in patients with the patellar rotation less than 3%. CONCLUSION: The measurement accuracy of coronal alignment of the lower limb on the FLWAP radiographs would be influenced by knee flexion, specifically when there is any subtle rotation of the knee joint in the axial plane. A strict patellar forward position without axial plane rotation of the knee could provide accurate results of the measurement even if there is a fixed flexion contracture of the knee.

The effect of medial open wedge high tibial osteotomy on the patellofemoral joint: comparative analysis according to the preexisting cartilage status.

BACKGROUND: Although it has been known that medial open wedge high tibial osteotomy (MOWHTO) would adversely affect the patellofemoral joint, no previous study examined the surgical outcome of MOWHTO according to the preexisting cartilage status of the patellofemoral joint. The aim of this study was to investigate the effect of MOWHTO on the patellofemoral joint with regard to objective and subjective aspects according to the preexisting cartilage status. METHODS: Ninety-two patients who underwent MOWHTO and a following second-look arthroscopic assessment were included in this study. The patients were divided into two groups according to the preexisting cartilage status of the patellofemoral joint: group 1 (International Cartilage Repair Society [ICRS] grade 2 or 3) and group 2 (ICRS grade 0 or 1). Comparative analysis was performed regarding clinical scores, radiographic parameters, and arthroscopic measurements between the two groups. RESULTS: Clinical outcomes showed overall improvement from baseline to the time of second-look operation, with no significant difference between the two groups at each time point. There were no significant differences in radiographic parameters between the two groups. Radiographic grade of patellofemoral osteoarthritis in both groups showed a tendency to progress, without statistical significance. In arthroscopic assessment, the size of the cartilage lesion on the patellofemoral joint increased with time in both groups (P = 0.003), but the degree of change over time between the two groups was not statistically significant. Consistently, there was no significant difference in the frequency of progression of cartilage lesion grade in the patellofemoral joint between the two groups. CONCLUSIONS: MOWHTO would contribute to osteoarthritis progression of the patellofemoral joint regardless of the preexisting cartilage status, without an association with clinical outcomes in short-term follow-up.

Multiscale Distribution Entropy Analysis of Short-Term Heart Rate Variability.

Electrocardiogram (ECG) signal has been commonly used to analyze the complexity of heart rate variability (HRV). For this, various entropy methods have been considerably of interest. The multiscale entropy (MSE) method, which makes use of the sample entropy (SampEn) calculation of coarse-grained time series, has attracted attention for analysis of HRV. However, the SampEn computation may fail to be defined when the length of a time series is not enough long. Recently, distribution entropy (DistEn) with improved stability for a short-term time series has been proposed. Here, we propose a novel multiscale DistEn (MDE) for analysis of the complexity of short-term HRV by utilizing a moving-averaging multiscale process and the DistEn computation of each moving-averaged time series. Thus, it provides an improved stability of entropy evaluation for short-term HRV extracted from ECG. To verify the performance of MDE, we employ the analysis of synthetic signals and confirm the superiority of MDE over MSE. Then, we evaluate the complexity of short-term HRV extracted from ECG signals of congestive heart failure (CHF) patients and healthy subjects. The experimental results exhibit that MDE is capable of quantifying the decreased complexity of HRV with aging and CHF disease with short-term HRV time series.

Development and assessment of a hand assist device: GRIPIT.

BACKGROUND: Although various hand assist devices have been commercialized for people with paralysis, they are somewhat limited in terms of tool fixation and device attachment method. Hand exoskeleton robots allow users to grasp a wider range of tools but are heavy, complicated, and bulky owing to the presence of numerous actuators and controllers. The GRIPIT hand assist device overcomes the limitations of both conventional devices and exoskeleton robots by providing improved tool fixation and device attachment in a lightweight and compact device. GRIPIT has been designed to assist tripod grasp for people with spinal cord injury because this grasp posture is frequently used in school and offices for such activities as writing and grasping small objects. METHODS: The main development objective of GRIPIT is to assist users to grasp tools with their own hand using a lightweight, compact assistive device that is manually operated via a single wire. GRIPIT consists of only a glove, a wire, and a small structure that maintains tendon tension to permit a stable grasp. The tendon routing points are designed to apply force to the thumb, index finger, and middle finger to form a tripod grasp. A tension-maintenance structure sustains the grasp posture with appropriate tension. Following device development, four people with spinal cord injury were recruited to verify the writing performance of GRIPIT compared to the performance of a conventional penholder and handwriting. Writing was chosen as the assessment task because it requires a tripod grasp, which is one of the main performance objectives of GRIPIT. RESULTS: New assessment, which includes six different writing tasks, was devised to measure writing ability from various viewpoints including both qualitative and quantitative methods, while most conventional assessments include only qualitative methods or simple time measuring assessments. Appearance, portability, difficulty of wearing, difficulty of grasping the subject, writing sensation, fatigability, and legibility were measured to assess qualitative performance while writing various words and sentences. Results showed that GRIPIT is relatively complicated to wear and use compared to a conventional assist device but has advantages for writing sensation, fatigability, and legibility because it affords sufficient grasp force during writing. Two quantitative performance factors were assessed, accuracy of writing and solidity of writing. To assess accuracy of writing, we asked subjects to draw various figures under given conditions. To assess solidity of writing, pen tip force and the angle variation of the pen were measured. Quantitative evaluation results showed that GRIPIT helps users to write accurately without pen shakes even high force is applied on the pen. CONCLUSIONS: Qualitative and quantitative results were better when subjects used GRIPIT than when they used the conventional penholder, mainly because GRIPIT allowed them to exert a higher grasp force. Grasp force is important because disabled people cannot control their fingers and thus need to move their entire arm to write, while non-disabled people only need to move their fingers to write. The tension-maintenance structure developed for GRIPIT provides appropriate grasp force and moment balance on the user's hand, but the other writing method only fixes the pen using friction force or requires the user's arm to generate a grasp force.

Microbial deglycosylation and ketonization of ginsenoside by Cladosporium cladosporioide and their anticancer activity.

Ginseng has been used for thousands of years in Asian countries as a traditional medicinal herb and has gained great popularity in the past decade. Ginsenosides are the major pharmacological components in ginseng. We here show that Cladosporium cladosporioide is able to convert the major ginsenoside Rb1 into four known metabolites (ginsenosides Rd, F2, CK and PPD) and two new metabolites [12ß-hydroxydammar-3-one-20(S)-O-ß-D-glucopyranoside (3-oxo-CK) and dammar-24-en-12ß,20(S)-diol-3-one (3-oxo-PPD)]. CK, PPD and 3-oxo-PPD were shown to have a potent antiproliferative activity against A549 lung cancer cells. We found that Rb1 → Rd → F2 → CK → PPD or 3-oxo-CK → 3-oxo-PPD represents the ginsenoside metabolic pathway.

Phytochemical constituents from the florets of tiger grass Thysanolaena latifolia from Nepal.

Phytochemical investigation on the florets of Thysanolaena latifolia leads to the isolation of a new compound 6″-O-acetylorientin-2″-O-α-L-rhamnopyranoside (1), named amrisoside and other 34 known compounds. The chemical structures of the compounds were determined from the interpretation of spectroscopic data including NMR, MS, and IR. This is the first report of phytochemical constituents from the monotypic genus Thysanolaena.

UPLC-MS/MS-Based Profiling of Eicosanoids in RAW264.7 Cells Treated with Lipopolysaccharide.

While both the pro- and anti-inflammatory effects of several eicosanoids have been widely studied, the degree of inflammation in cells that results from various eicosanoids has yet to be comprehensively studied. The objective of this study was to assess the effect of lipopolysaccharide (LPS) treatment on eicosanoid content in RAW264.7 cells. An Ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS)-based profiling method was used to analyze the eicosanoid contents of RAW264.7 cells treated with different LPS concentrations. The profiling data were subjected to statistical analyses, such as principal component analysis (PCA) and hierarchical clustering analysis. LPS treatment increased nitric oxide production and secretion of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, in a concentration-dependent manner. In total, 79 eicosanoids were identified in the cells. RAW264.7 cells treated with different LPS concentrations were well differentiated in the PCA score plot. A heatmap was used to identify the eicosanoids that were up- or down-regulated according to the degree of inflammation and LPS concentration. Thirty-nine eicosanoids were upregulated and seven were down-regulated by LPS treatment in a concentration-dependent manner. Our novel UPLC-MS/MS technique can profile eicosanoids, and can evaluate the correlations between inflammation and eicosanoid metabolism.

Three New Isoprenylated Flavonoids from the Root Bark of Morus alba.

Phytochemical investigation of the root bark of Morus alba has led to the isolation and identification of three new isoprenylated flavonoids, namely sanggenon U (1), sanggenon V (2), and sanggenon W (3), along with four known isoprenylated flavonoids: euchrenone a7 (4), sanggenon J (5), kuwanon E (6), and kuwanon S (7). All compounds were isolated by repeated silica gel (SiO2), octadecyl SiO2 (ODS), and Sephadex LH-20 open column chromatography. The structure of the compounds were determined based on spectroscopic analyses, including nuclear magnetic resonance (NMR), mass spectrometry (MS), circular dichroism (CD), and infrared (IR). In addition, compounds 1-4 were isolated for the first time from the root bark of M. alba in this study.

Antimelanogenic Effects of Picrionoside A Isolated from the Leaves of Korean Ginseng.

This study was initiated to isolate active metabolites from the leaves of Panax ginseng. Among them, picrionoside A, a megastigmane glucoside, was isolated from the leaves of P. ginseng C. A. MAYER and its chemical structure was determined based on spectroscopic methods, including FAB-MS, one-dimensional (1D)-NMR, 2D-NMR, and IR spectroscopy. Picrionoside A from P. ginseng has not been investigated previously, and its biological or pharmaceutical activities have not been reported elsewhere. The IC50 value of mushroom tyrosinase-inhibitory activity of picrionoside A was 9.8 µM, and the rate of inhibition of synthesized melanin content in melan-a cells was 17.1% at a concentration of 80 µM without cytotoxicity. Furthermore, picrionoside A dramatically reduced body pigmentation in the zebrafish model. Taken together, the results suggest that picrionoside A isolated from the leaves of P. ginseng may be an effective skin-whitening agent that could be a potent candidate material in the cosmetic industry.

Global Profiling of Various Metabolites in Platycodon grandiflorum by UPLC-QTOF/MS.

In this study, a method of metabolite profiling based on UPLC-QTOF/MS was developed to analyze Platycodon grandiflorum. In the optimal UPLC, various metabolites, including major platycosides, were separated well in 15 min. The metabolite extraction protocols were also optimized by selecting a solvent for use in the study, the ratio of solvent to sample and sonication time. This method was used to profile two different parts of P. grandiflorum, i.e., the roots of P. grandiflorum (PR) and the stems and leaves of P. grandiflorum (PS), in the positive and negative ion modes. As a result, PR and PS showed qualitatively and quantitatively different metabolite profiles. Furthermore, their metabolite compositions differed according to individual plant samples. These results indicate that the UPLC-QTOF/MS-based profiling method is a good tool to analyze various metabolites in P. grandiflorum. This metabolomics approach can also be applied to evaluate the overall quality of P. grandiflorum, as well as to discriminate the cultivars for the medicinal plant industry.

The potential of minor ginsenosides isolated from the leaves of Panax ginseng as inhibitors of melanogenesis.

Three minor ginsenosides, namely, ginsenoside Rh6 (1), vina-ginsenoside R4 (2) and vina-ginsenoside R13 (3), were isolated from the leaves of hydroponic Panax ginseng. The chemical structures were determined based on spectroscopic methods, including fast atom bombardment mass spectroscopy (FAB-MS), 1D-nuclear magnetic resonance (NMR), 2D-NMR, and, infrared (IR) spectroscopy. The melanogenic inhibitory activity of compounds 1, 2 and 3 was 23.9%, 27.8% and 35.2%, respectively, at a concentration of 80 µM. Likewise, the three compounds showed inhibitory activity on body pigmentation on a zebrafish model, which is commonly used as a model for biomedical or cosmetic research. These results from in vitro and in vivo systems suggest that the three aforementioned compounds isolated from Panax ginseng may have potential as new skin whitening compounds.

Two New Cyototoxic Cardenolides from the Whole Plants of Adonis multiflora Nishikawa & Koki Ito.

A phytochemical investigation of the whole plants of Adonis multiflora Nishikawa & Koki Ito. resulted in the isolation and identification of two new cardenolides--adonioside A (1) and adonioside B (6)--as well as four known cardenolides: tupichinolide (2) oleandrine (3), cryptostigmin II (4), and cymarin (5). Their structures were elucidated on the basis of NMR, MS, and IR spectroscopic analyses. Compounds 1, 2, 5, and 6 showed significant cytotoxicity against six human cancer cell lines (HCT-116, HepG2, HeLa, SK-OV-3, and SK-MEL-5, and SK-BR-3).

Microbial ketonization of ginsenosides F1 and C-K by Lactobacillus brevis.

Ginsenosides are the major pharmacological components in ginseng. We isolated lactic acid bacteria from Kimchi to identify microbial modifications of ginsenosides. Phylogenetic analysis of 16S rRNA gene sequences indicated that the strain DCY65-1 belongs to the genus Lactobacillus and is most closely related to Lactobacillus brevis. On the basis of TLC and HPLC analysis, we found two metabolic pathways: F1 → 6α,12ß-dihydroxydammar-3-one-20(S)-O-ß-D-glucopyranoside and C-K → 12ß-hydroxydammar-3-one-20(S)-O-ß-D-glucopyranoside. These results suggest that strain DCY65-1 is capable of potent ketonic decarboxylation, ketonizing the hydroxyl group at C-3. The F1 metabolite had a more potent inhibitory effect on mushroom tyrosinase than did the substrate. Therefore, the F1 and C-K derivatives may be more pharmacologically active compounds, which should be further characterized.

High-performance, transparent, and stretchable electrodes using graphene-metal nanowire hybrid structures.

Transparent electrodes that can remain electrically conductive and stable under large mechanical deformations are highly desirable for applications in flexible and wearable electronics. This paper describes a comprehensive study of the electrical, optical, and mechanical properties of hybrid nanostructures based on two-dimensional graphene and networks of one-dimensional metal nanowires, and their use as transparent and stretchable electrodes. Low sheet resistance (33 Ω/sq) with high transmittance (94% in visible range), robust stability against electric breakdown and oxidation, and superb flexibility (27% in bending strain) and stretchability (100% in tensile strain) are observed, and these multiple functionalities of the hybrid structures suggest a future promise for next generation electronics. The use of hybrid electrodes to fabricate oxide semiconductor transistors and single-pixel displays integrated on wearable soft contact lenses with in vivo tests are demonstrated.

Flavonoids from Machilus japonica stems and their inhibitory effects on LDL oxidation.

Stems of Machilus japonica were extracted with 80% aqueous methanol (MeOH) and the concentrated extract was successively extracted with ethyl acetate (EtOAc), normal butanol (n-BuOH), and water. Six flavonoids were isolated from the EtOAc fraction: (+)-taxifolin, afzelin, (-)-epicatechin, 5,3'-di-O-methyl-(-)-epicatechin, 5,7,3'-tri-O-methyl-(-)-epicatechin, and 5,7-di-O-methyl-3',4'-methylenedioxyflavan-3-ol. The chemical structures were identified using spectroscopic data including NMR, mass spectrometry and infrared spectroscopy. This is the first report of isolation of these six compounds from M. japonica. The compounds were evaluated for their diphenyl picryl hydrazinyl scavenging activity and inhibitory effects on low-density lipoprotein oxidation. Compounds 1 and 3-6 exhibited DPPH antioxidant activity equivalent with that of ascorbic acid, with half maximal inhibitory concentration (IC50) values of 0.16, 0.21, 0.17, 0.15 and 0.07 mM, respectively. The activity of compound 1 was similar to the positive control butylated hydroxytoluene, which had an IC50 value of 1.9 µM, while compounds 3 and 5 showed little activity. Compounds 1, 3, and 5 exhibited LDL antioxidant activity with IC50 values of 2.8, 7.1, and 4.6 µM, respectively.

Multiscale distribution entropy analysis of short epileptic EEG signals.

This paper proposes an information-theoretic measure for discriminating epileptic patterns in short-term electroencephalogram (EEG) recordings. Considering nonlinearity and nonstationarity in EEG signals, quantifying complexity has been preferred. To decipher abnormal epileptic EEGs, i.e., ictal and interictal EEGs, via short-term EEG recordings, a distribution entropy (DE) is used, motivated by its robustness on the signal length. In addition, to reflect the dynamic complexity inherent in EEGs, a multiscale entropy analysis is incorporated. Here, two multiscale distribution entropy (MDE) methods using the coarse-graining and moving-average procedures are presented. Using two popular epileptic EEG datasets, i.e., the Bonn and the Bern-Barcelona datasets, the performance of the proposed MDEs is verified. Experimental results show that the proposed MDEs are robust to the length of EEGs, thus reflecting complexity over multiple time scales. In addition, the proposed MDEs are consistent irrespective of the selection of short-term EEGs from the entire EEG recording. By evaluating the Man-Whitney U test and classification performance, the proposed MDEs can better discriminate epileptic EEGs than the existing methods. Moreover, the proposed MDE with the moving-average procedure performs marginally better than one with the coarse-graining. The experimental results suggest that the proposed MDEs are applicable to practical seizure detection applications.

Potential neuroprotective flavonoid-based inhibitors of CDK5/p25 from Rhus parviflora.

Rhus parviflora (Anacardiaceae) is an indigenous medicinal shrub found in South Asia with flavonoid rich edible fruit. This study examined flavonoid derivatives of R. parviflora fruit with CDK5/p25 inhibition activity. Evaluation by in vitro assay and docking simulations for CDK5/p25 revealed that the aurones, sulfuretin (1) and aureusidin (2), the aurone glycoside, aureusidin-6-O-ß-D-glucopyranoside (3) and hovetrichoside C (4), the flavonoid glycoside, quercetin-3-O-ß-D-galactopyranoside (5), and the biflavonoid, cupressuflavone (6), had the potential to inhibit CDK5/p25, which could be useful in the treatment of neurodegenerative disorders such as Alzheimer's disease. Compound2 showed the significant in vitro inhibition capacity (IC50 value of 4.81 µM) as well as binding affinity with docking energy of -8.73 (kcal/mol) for active sites CYS83 and GLN130 of CDK5/p25 enzyme in comparison to reference compound R-roscovitine.

Neolignans from the fruits of Magnolia obovata and their inhibition effect on NO production in LPS-induced RAW 264.7 cells.

Three new neolignans, named 9-methoxyobovatol (6), magnobovatol (7), and 2-hydroxyobovaaldehyde (9), along with six known ones, magnolol (1), honokiol (2), isomagnolol (3), obovatol (4), obovatal (5), and obovaaldehyde (8), were isolated from the fruits of Magnolia obovata using silica gel and ODS column chromatography. From the results of spectroscopic data including EIMS, IR, 1H- and 13C-NMR, DEPT, and 2D-NMR (gCOSY, gHSQC, gHMBC), the chemical structures were determined. All isolated compounds were evaluated for inhibition activity on nitric oxide production in LPS-induced RAW 264.7 cells, and compounds 1-4, 6, 7, and 9 showed significant activity with IC50 values of 15.8 ± 0.3, 3.3 ± 1.2, 14.1 ± 0.9, 6.2 ± 1.2, 14.8 ± 2.3, 14.2 ± 1.2, and 14.8 ± 3.2 µM, respectively, without any visible toxic effect.

Brazilin inhibits growth and induces apoptosis in human glioblastoma cells.

Brazilin, isolated from the methanol extract of the heart wood of Caesalpinia sappan, sensitizes cancer cells to apoptosis. Glioblastoma multiforme (GBM), which accounts for most cases of central nervous system malignancy, has a very poor prognosis and lacks effective therapeutic interventions. We, therefore, investigated the effects of different concentrations of and different periods of exposure to brazilin on cell proliferation and apoptosis in the glioma U87 cell line. Cell proliferation was investigated by MTT assays and growth curve analysis, apoptosis was assessed by FACS analysis and western blot studies. Brazilin showed dose-dependent inhibition of cell proliferation and induction of apoptosis in glioma cells. It also increased the ratio of cleaved poly-(ADP)-ribose polymerase and decreased the expression of caspase-3 and caspase-7.