Phenylalkyl Glycosides from the Flowers of Brugmansia arborea L. and Their Radical Scavenging Effect and Protective Effect on Pancreatic Islets Damaged by Alloxan in Zebrafish (Danio rerio) Larvae.

The study aimed to investigate the antioxidant and antidiabetic activity of Brugmansia arborea L. flower extracts, solvent fractions, and isolated compounds. B. arborea L flowers were extracted with aqueous methanol, and concentrated extract was successively partitioned into EtOAc, n-BuOH, and H2O fractions. Repeated silica gel and octadecyl silica gel column chromatographies for EtOAc and n-BuOH fractions led to the isolation of a new phenylalkyl glycoside (6), along with five known ones. Several spectroscopic data led to the structure determination of one new phenylalky glycoside as brugmansioside C (named) (6) and five known ones as benzyl-O-ß-D-glucopyranoside (1), benzyl-O-ß-D-glucosyl-(1→6)-ß-D-glucopyranoside (2), 2-phenylethyl-O-ß-D-glucopyranoside (3), 2-phenylethyl-O-ß-D-glucosyl-(1→6)-ß-D-glucopyranoside (4), and 3-phenylpropyl-O-ß-D-glucopyranoside (5). The five known ones (1-5) were isolated from B. arborea flowers for the first time in this study. The extract, solvent fractions, and all isolated compounds showed radical scavenging activities using ABTS radical, and EtOAc fraction showed the highest scavenging capacity, whereas compounds 2, 4, and 6 did not display the capacity to use the DPPH radical. The extract, solvent fractions, and all isolated compounds showed a protective effect on pancreatic islets damaged by alloxan treatment in zebrafish larvae. The pancreatic islet size treated with EtOAc, n-BuOH fractions, and all compounds significantly increased by 64.0%, 69.4%, 82.0%, 89.8%, 80.0%, 97.8%, 103.1%, and 99.6%, respectively, compared to the alloxan-induced group. These results indicate that B. arborea flowers and their isolated compounds are useful as potential antioxidant and antidiabetic agents.

Aurones and Flavonols from Coreopsis lanceolata L. Flowers and Their Anti-Oxidant, Pro-Inflammatory Inhibition Effects, and Recovery Effects on Alloxan-Induced Pancreatic Islets in Zebrafish.

(1) Background: Many flavonoids have been reported to exhibit pharmacological activity; a preparatory study confirmed that Coreopsis lanceolata flowers (CLFs) contained high flavonoid structure content; (2) Methods: CLFs were extracted in aqueous methanol (MeOH:H2O = 4:1) and fractionated into acetic ester (EtOAc), normal butanol (n-BuOH), and H2O fractions. Repeated column chromatographies for two fractions led to the isolation of two aurones and two flavonols; (3) Results: Four flavonoids were identified based on a variety of spectroscopic data analyses to be leptosidin (1), leptosin (2), isoquercetin (3), and astragalin (4), respectively. This is the first report for isolation of 2-4 from CLFs. High-performance liquid chromatography (HPLC) analysis determined the content levels of compounds 1-4 in the MeOH extract to be 2.8 ± 0.3 mg/g (1), 17.9 ± 0.9 mg/g (2), 3.0 ± 0.2 mg/g (3), and 10.9 ± 0.9 mg/g (4), respectively. All isolated compounds showed radical scavenging activities and recovery activities in Caco-2, RAW264.7, PC-12, and HepG2 cells against reactive oxygen species. MeOH extract, EtOAc fraction, and 1-3 suppressed NO formation in LPS-stimulated RAW 264.7 cells and decreased iNOS and COX-2 expression. Furthermore, all compounds recovered the pancreatic islets damaged by alloxan treatment in zebrafish; (4) Conclusions: The outcome proposes 1-4 to serve as components of CLFs in standardizing anti-oxidant, pro-inflammatory inhibition, and potential anti-diabetic agents.

Inter-subject correlations during natural viewing: A filter-bank approach.

A central question in neuroscience is how the brain processes real-world sensory input. For decades most classical studies focus on carefully controlled artificial stimuli. More recently researchers started to investigate brain activity under more realistic conditions. The main challenge in this setting is the analysis of the complex signals obtained with modern neuroimaging methods in response to natural stimuli. Inter-subject correlations (ISCs) have become a popular paradigm to study brain activation under natural stimulation. The underlying assumption of this analysis is that features of natural stimuli that are perceived and processed by all subjects exposed to the same stimulus result in similar activation patterns across subjects. Higher degrees of realism in stimulation, for instance audiovisual stimulation is more realistic than auditory stimulation, is usually associated with higher ISC values. We can confirm these findings in experiments in which we present a movie stimulus with varying degrees of realism. Extending previous findings we highlight the importance of artifact removal when evaluating ISCs and show that the impact of realism in natural stimulation on ISCs is frequency-dependent. A major challenge associated with this type of analysis is that it can be difficult to attribute the correlation strength to the physiological process of interest. In this study, we demonstrate that ISCs of neural activation as measured by electroencephalogram (EEG) recordings are influenced significantly by non-neural artifacts such as occulograms. Our findings highlight the potential of inter-subject correlations as a biomarker for immersion: If more realistic stimuli consistently lead to higher inter-subject correlations, then inter-subject correlations can serve as a quantitative marker for how engaging audiovisual stimuli are perceived.Clinical relevance- Future research will evaluate if correlation levels among subjects, who are exposed to natural stimuli are affected by neurological diseases such as Alzheimers, Parkinsons, and Schizophrenia among others.

LC-MS-Based Lipidomic Analysis of Serum Samples from Spontaneously Hypertensive Rats Treated with an Extract of Acanthopanax sessiliflorus Fruits.

Recently, lipidomics has revealed that many diseases are highly associated with altered lipid metabolism, as in the case of hypertension affecting serum lipid metabolism. In this study, an LC-MS-based lipidomic approach was used to profile serum lipids in spontaneously hypertensive rats (SHRs) treated with an extract of Acanthopanax sessiliflorus fruits (ASF), to elucidate the serum lipid metabolism alteration by hypertension and the treatment of a drug or ASF. First, UPLC-QTOF/MS profiled a total of 208 lipids from six pooled samples of normal controls, SHR, SHR + 100 mg/kg of drug, and SHR + ASF 200, 400, or 600 mg/kg. These six groups were differentiated by the PCA and sPLS-DA, and 120 lipid species were identified as differentially regulated lipids (DRLs) by ANOVA (p values < 0.05). Second, UPLC-QqQ/MS was used for the target profiling of 120 DRLs from individual samples of the six groups. Using an ANOVA, 67 lipids (38 TGs, 4 DGs, 17 PCs, 2 PEs, and 6 LPCs) were selected as validated DRLs. The mostly altered lipids, such as TG (62:13), TG (60:13), PC (34:4), PC (36:5), and PC (38:2), were decreased in SHR compared to the normal control, and received little by treatment with ASF. These results demonstrated the correlation between hypertension and serum lipid metabolism. Furthermore, both drug and ASF treatment similarly altered the lipid profiles of SHRs. Finally, we found that DRLs have the potential to help us to interpret the lipid metabolism of hypertension.

Robust detection of event-related potentials in a user-voluntary short-term imagery task.

Event-related potentials (ERPs) represent neuronal activity in the brain elicited by external visual or auditory stimulation and are widely used in brain-computer interface (BCI) systems. The ERP responses are elicited a few milliseconds after attending to an oddball stimulus; target and non-target stimuli are repeatedly flashed, and the ERP trials are averaged over time in order to improve their decoding accuracy. To reduce this time-consuming process, previous studies have attempted to evoke stronger ERP responses by changing certain experimental parameters like color, size, or the use of a face image as a target symbol. Since these exogenous potentials can be naturally evoked by merely looking at a target symbol, the BCI system could generate unintended commands while subjects are gazing at one of the symbols in a non-intentional mental state. We approached this problem of unintended command generation by assuming that a greater effort by the user in a short-term imagery task would evoke a discriminative ERP response. Three tasks were defined: passive attention, counting, and pitch-imagery. Users were instructed to passively attend to a target symbol, or to perform a mental tally of the number of target presentations, or to perform the novel task of imagining a high-pitch tone when the target symbol was highlighted. The decoding accuracy were 71.4%, 83.5%, and 89.2% for passive attention, counting, and pitch-imagery, respectively, after the fourth averaging procedure. We found stronger deflections in the N500 component corresponding to the levels of mental effort (passive attention: -1.094 ±0.88 µV, counting: -2.226 ±0.97 µV, and pitch-imagery: -2.883 ±0.74 µV), which highly influenced the decoding accuracy. In addition, the rate of binary classification between passive attention and pitch-imagery tasks was 73.5%, which is an adequate classification rate that motivated us to propose a two-stage classification strategy wherein the target symbols are estimated in the first stage and the passive or active mental state is decoded in the second stage. In this study, we found that the ERP response and the decoding accuracy are highly influenced by the user's voluntary mental tasks. This could lead to a useful approach in practical ERP systems in two respects. Firstly, the user-voluntary tasks can be easily utilized in many different types of BCI systems, and performance enhancement is less dependent on the manipulation of the system's external, visual stimulus parameters. Secondly, we propose an ERP system that classifies the brain state as intended or unintended by considering the measurable differences between passively gazing and actively performing the pitch-imagery tasks in the EEG signal thus minimizing unintended commands to the BCI system.

The Effect of Vitamin D Deficiency Correction on the Outcomes in Women After Carpal Tunnel Release.

PURPOSE: Studies suggest that vitamin D supplementation improves myelination and recovery after nerve injuries. The purpose of this study was to evaluate whether correction of vitamin D level leads to better surgical outcomes in women with both carpal tunnel syndrome (CTS) and vitamin D deficiency. METHODS: We retrospectively reviewed 84 vitamin D-deficient women with CTS who underwent carpal tunnel release and then received daily vitamin D supplementation of 1,000 IU vitamin D for 6 months. We also reviewed 35 control patients who were vitamin D-nondeficient at baseline and thus did not receive the supplementation. At baseline and 6 months after surgery, we measured serum vitamin D levels, the Disabilities of the Arm, Shoulder, and Hand (DASH) score, motor conduction velocity, and grip and pinch strengths. We compared the outcomes of CTS related to vitamin D levels. We also correlated baseline and follow-up vitamin D levels with the assessed parameters. RESULTS: At 6 months, 59 patients became vitamin D-nondeficient (≥ 20 ng/mL) and 25 were still vitamin D-deficient (< 20 ng/mL). Patients who became vitamin D-nondeficient had subtle but better DASH scores than patients who were still vitamin D-deficient or the control patients. Vitamin D levels at 6 months were found to have significant correlation with the DASH score at 6 months. Vitamin D levels at 6 months did not have significant correlation with motor conduction velocity or grip and pinch strengths. CONCLUSIONS: Women with CTS and vitamin D deficiency showed subtle but better DASH scores after surgery when vitamin D deficiency was corrected by supplementation. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Dietary zerumbone, a sesquiterpene, ameliorates hepatotoxin-mediated acute and chronic liver injury in mice.

Acute liver injury (ALI) is a life-threatening clinical syndrome. Long-lasting liver injury can lead to chronic hepatic inflammation and fibrogenic responses. Zerumbone (ZER), the main constituent of rhizomes of Zingiber zerumbet Smith, has a variety of functions including anticancer activity. We investigated the role of ZER on the progression of hepatotoxin-induced liver injury. Single or repeated injection of CCl4 was used to induce acute or chronic liver injury, respectively. Mice were orally administered with ZER (10, 50 mg/kg) during the experimental period. Histopathologic analysis and serum biochemical levels revealed that ZER had hepatoprotective activities against ALI. Similar effects of ZER on injured livers were confirmed by analyses of inflammation and apoptosis-related genes. Western blot analysis showed that protein levels of apoptotic molecules were decreased, whereas antiapoptotic protein levels were conversely increased in injured livers treated with ZER. Furthermore, chronic liver injury and its associated fibrogenesis in mice were reduced by ZER treatment. These findings from our in vivo experiments further indicate that ZER could alleviate hepatocellular toxicity and inhibit activation of primary hepatic stellate cells. Our results suggest that ZER might have potential as a safe and prophylactic alternative to prevent acute and chronic liver injury.

Regulatory Effects of Black Rice Extract on Helicobacter pylori Infection-Induced Apoptosis.

SCOPE: Black rice extract (BRE) contains cyanidin 3-O-glucoside (C3G), an anthocyanin, as the major component. In this study, we found that BRE inhibits the mRNA and protein expression of genes encoding cytotoxin-associated protein A (cagA) and vacuolating protein A (vacA) in Helicobacter pylori 60190 strain. METHODS AND RESULTS: We performed RT-PCR and western blotting to show that BRE inhibits the mRNA and protein expression of SecA. Because SecA is involved in VacA export in bacteria, our result suggests a positive correlation between BRE-induced inhibition of secA expression and VacA secretion. Further, we perform MTT assay and flow cytometry to show that BRE decreases the apoptosis of H. pylori-infected KATO III cells. Finally, we perform western blotting to show that the cell-protective effect of BRE is associated with decreased levels of active proapoptotic proteins caspases and PARP and increased levels of antiapoptotic proteins survivin and XIAP in H. pylori-infected cells. CONCLUSION: Thus, our results indicate that BRE acts as a potent inhibitor of the biogenesis of H. pylori virulence proteins and decreases the apoptosis of H. pylori-infected cells. Moreover, our results suggest that BRE can be used to exert beneficial effects in patients with gastroduodenal diseases caused by H. pylori.

Corrosion resistance and bioactivity enhancement of MAO coated Mg alloy depending on the time of hydrothermal treatment in Ca-EDTA solution.

In this study, a two-step surface treatment was developed to restrain the rapid primary degradation of a biodegradable Mg alloy and to improve their biocompatibility. Micro arc oxidation (MAO) coating was performed in alkaline electrolytes such as 1.0 M NaOH with 0.1 M glycerol and 0.1 M Na3PO4. Hydrothermal treatment was performed in 0.1 M Ca-EDTA (C10H12CaN2Na2O8) and 0.5 M NaOH solution at 90 °C for different times (6, 12, 24, and 48 h). The film morphology and chemical properties were evaluated by XRD and FE-SEM. The electrochemical and corrosion behaviors were examined in the simulated body fluid, and cytotoxicity was assessed using MC3T3-E1 cells. After MAO coating, an oxide layer containing [Formula: see text] formed on the surface. During the hydrothermal treatment in Ca-EDTA solution, calcium phosphate and Mg(OH)2 were produced via a reaction between [Formula: see text] on the surface and Ca2+ in solution. The layer with ceramics and oxides was grown on the surface with increasing hydrothermal treatment time, and improved the surface corrosion resistance. The 24 h hydrothermal-treated group showed the lowest immersion corrosion rate and high cell viability. Therefore, this treatment was the most favorable surface modification for improving the initial corrosion resistance and bioactivity of the biodegradable Mg alloy.

Comparative effectiveness and cost-effectiveness of Chuna manual therapy versus conventional usual care for nonacute low back pain: study protocol for a pilot multicenter, pragmatic randomized controlled trial (pCRN study).

BACKGROUND: While Chuna manual therapy is a Korean manual therapy widely used primarily for low back pain (LBP)-related disorders in Korea, well-designed studies on the comparative effectiveness of Chuna manual therapy are scarce. METHODS/DESIGN: This study is the protocol for a three-armed, multicenter, pragmatic randomized controlled pilot trial. Sixty severe nonacute LBP patients (pain duration of at least 3 weeks, Numeric Rating Scale (NRS) ≥5) will be recruited at four Korean medicine hospitals. Participants will be randomly allocated to the Chuna group (n = 20), usual care group (n = 20), or Chuna plus usual care group (n = 20) for 6 weeks of treatment. Usual care will consist of orally administered conventional medicine, physical therapy, and back pain care education. The trial will be conducted with outcome assessor and statistician blinding. The primary endpoint will be NRS of LBP at week 7 post randomization. Secondary outcomes include NRS of leg pain, the Oswestry Disability Index (ODI), the Patient Global Impression of Change (PGIC), the Credibility and Expectancy Questionnaire, lumbar range of motion (ROM), the EuroQol-5 Dimension (EQ-5D) health survey, the Health Utility Index III (HUI-III), and economic evaluation and safety data. Post-treatment follow-ups will be conducted at 1, 4, and 10 weeks after conclusion of treatment. DISCUSSION: This study will assess the comparative effectiveness of Chuna manual therapy compared to conventional usual care. Costs and effectiveness (utility) data will be analyzed for exploratory cost-effectiveness analysis. If this pilot study does not reach a definite conclusion due to its small sample size, these results will be used as preliminary results to calculate sample size for future large-scale clinical trials and contribute in the assessment of feasibility of a full-scale multicenter trial. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), KCT0001850 . Registered on 17 March 2016.

Ethanol extract of Pinus koraiensis leaves containing lambertianic acid exerts anti-obesity and hypolipidemic effects by activating adenosine monophosphate-activated protein kinase (AMPK).

BACKGROUND: In this study, we investigated the anti-obesity and anti-hyperlipidemic mechanisms of lambertianic acid (LA) isolated from Pinus koraiensis leaves and the ethanol extract of Pinus koraiensis leaves (EPK), both in vitro and in vivo. METHODS: Differentiated 3T3L-1 cells were treated with EPK (25 or 50 µg/mL) or LA (200 µM) and analyzed by western blotting or RT-PCR. In vitro, lipid accumulation of adipocytes was observed using Oil-Red-O staining and triglyceride analysis. The contribution of AMPK to anti-obesity activity was assessed by siRNA-mediated AMPK knockdown. After AMPK silencing, expression of AMPK was observed by western blotting. To confirm the in vitro activity, an animal study was conducted by administering a normal diet, HFD, and EPK for 6 weeks. Obesity-related physiological parameters and protein levels were measured. RESULTS: LA induced the expression of p-AMPK and inhibited PPARγ, C/EBP α, adiponectin, FAS, SREBP-1, and HMGCR expression. EPK containing LA significantly decreased lipid accumulation and triglyceride levels in the differentiated 3 T3-L1 cells. EPK treatment suppressed the expression of adipogenic transcription factors, FABP, GPDH, and cholesterol-synthesis-related factors in the differentiated 3 T3-L1 cells. EPK increased the expression of p-AMPK. The effects of EPK were reversed on inhibiting AMPK by using AMPK siRNA and compound C. In vivo analysis showed that body weight gain, serum triglyceride, total cholesterol, LDL cholesterol and AI value in the EPK treatment group were lower than those in the HFD control group. EPK induced the expression of p-AMPK and inhibited PPARγ in liver and adipose tissue. CONCLUSIONS: Overall, the results suggest that EPK containing LA exerts significant anti-obesity and cholesterol-lowering effects by activating AMPK.

Inhibitory effect of imperatorin on insulin-like growth factor-1-induced sebum production in human sebocytes cultured in vitro.

AIMS: Acne is a common skin disease that originates in the sebaceous gland. The pathogenesis of acne is very complex, involving the increase of sebum production and perifollicular inflammation. In this study, we screened the anti-lipogenic material and demonstrated its effect using cultured human sebocytes. MAIN METHODS: Normal human sebocytes were cultured by explanting the sebaceous glands. To evaluate the anti-lipogenic effect, sebocytes were treated with test materials and (14)C-acetate incorporation assay was performed. KEY FINDINGS: To screen the anti-lipogenic materials, we tested the effect of many herbal plant extracts. We found that Angelica dahurica extract inhibited the insulin-like growth factor-1 (IGF-1)-induced sebum production in terms of squalene synthesis in sebocytes. Furthermore, imperatorin isolated from A. dahurica showed remarkable inhibitory effect on squalene production as well as squalene synthase promoter activity. To investigate the putative action mechanism, we tested the effect of imperatorin on intracellular signaling. The results showed that imperatorin inhibited IGF-1-induced phosphorylation of Akt. In addition, imperatorin significantly down-regulated PPAR-γ and SREBP-1, the important transcription factors for lipid synthesis. SIGNIFICANCE: These results suggest that imperatorin has a potential for reducing sebum production in sebocytes, and can be applicable for acne treatment.

Anticancer activity of Ashwagandha against human head and neck cancer cell lines.

BACKGROUND: The aim of this study was to determine the apoptotic activity of methanol extract of Ashwagandha (MEAG) and in human head and neck squamous cell carcinoma (HNSCC) cells and to investigate the underlying mechanisms. METHODS: We investigated the effects of MEAG on programmed cell death in HNSCC cells using a Live/Dead assay, detection of nuclear morphologic changes, Mitotracker, siRNA knockdown, and RT-PCR. RESULTS: Treatment with MEAG showed dose-dependent growth-inhibitory activity that attribute to caspase-dependent apoptosis. Loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase 9 suggested that MEAG leads to activation of mitochondria-mediated apoptosis. MEAG selectively upregulated the expression of Bim protein at the transcriptional level and induced the translocation of Bim into the mitochondria. Knockdown of Bim by siRNA partially blocked MEAG-mediated apoptosis. MEAG also caused an increase in truncated Bid (t-Bid), cleaved caspase-8, and death receptor 5 (DR5). Interestingly, withaferin A (WA), a bioactive component of MEAG, clearly induced apoptosis accompanied by upregulation of Bim, t-Bid, caspase-8, and DR5 similar to the effects of MEAG. CONCLUSIONS: These suggest that MEAG and WA may be potential natural materials for the treatment of HNSCC.

The Mechanism Underlying the Antibacterial Activity of Shikonin against Methicillin-Resistant Staphylococcus aureus.

Shikonin (SKN), a highly liposoluble naphthoquinone pigment isolated from the roots of Lithospermum erythrorhizon, is known to exert antibacterial, wound-healing, anti-inflammatory, antithrombotic, and antitumor effects. The aim of this study was to examine SKN antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The SKN was analyzed in combination with membrane-permeabilizing agents Tris and Triton X-100, ATPase inhibitors sodium azide and N,N'-dicyclohexylcarbodiimide, and S. aureus-derived peptidoglycan; the effects on MRSA viability were evaluated by the broth microdilution method, time-kill test, and transmission electron microscopy. Addition of membrane-permeabilizing agents or ATPase inhibitors together with a low dose of SKN potentiated SKN anti-MRSA activity, as evidenced by the reduction of MRSA cell density by 75% compared to that observed when SKN was used alone; in contrast, addition of peptidoglycan blocked the antibacterial activity of SKN. The results indicate that the anti-MRSA effect of SKN is associated with its affinity to peptidoglycan, the permeability of the cytoplasmic membrane, and the activity of ATP-binding cassette (ABC) transporters. This study revealed the potential of SKN as an effective natural antibiotic and of its possible use to substantially reduce the use of existing antibiotic may also be important for understanding the mechanism underlying the antibacterial activity of natural compounds.

Holmium laser enucleation of the prostate is effective in the treatment of symptomatic benign prostatic hyperplasia of any size including a small prostate.

PURPOSE: Although transurethral resection of the prostate (TURP) is considered the standard surgical treatment for benign prostatic hyperplasia (BPH), Holmium laser enucleation of the prostate (HoLEP) is replacing TURP. We compared TURP with HoLEP with matching for prostate size. MATERIALS AND METHODS: We retrospectively reviewed the medical charts of patients who underwent TURP and HoLEP performed by one surgeon at our institute. All patients were categorized into 3 groups on the basis of prostate size (group 1, <40 g; group 2, 40-79 g; and group 3, >80 g), and 45 patients were selected for each method. RESULTS: No major intraoperative complications were encountered. The mean resected tissue weight was 6.3, 18.3, and 28.0 g for groups 1, 2, and 3, respectively, for TURP and 8.7, 25.0, and 39.8 g, respectively, for HoLEP. The mean operation time was 51.8, 89.3, and 101.9 minutes for TURP and 83.6, 122.8, and 131.2 minutes for HoLEP in groups 1, 2, and 3, respectively. HoLEP had better resection efficacy than TURP for any size prostate, but there was no statistical difference between the methods. Both methods resulted in an immediate and significant improvement of International Prostate Symptom Score, peak urinary flow rates, and postvoid residual urine volume. CONCLUSIONS: HoLEP is effective for BPH treatment, regardless of prostate size, even in a small prostate. The perioperative morbidity of HoLEP is also comparable to that of TURP.

The effects of adding elements of zinc and magnesium on ag-cu eutectic alloy for warming acupuncture.

The warming acupuncture for hyperthermia therapy is made of STS304. However, its needle point cannot be reached to a desirable temperature due to heat loss caused by low thermal conductivity, and the quantification of stimulation condition and the effective standard establishment of warming acupuncture are required as a heat source. Accordingly, in this study, after Ag-Cu alloys with different composition ratios were casted and then mixed with additives to improve their physical and mechanical properties, the thermal conductivity and biocompatibility of the alloy specimens were evaluated for selecting suitable material. Ag-Cu binary alloys and ternary alloys added 5 wt% Zn or 2 wt% Mg were casted and then cold drawn to manufacture needles for acupuncture, and their physical properties, thermal conductivity, and biocompatibility were evaluated for their potential use in warming acupuncture. The results of this study showed that the physical and mechanical properties of the Ag-Cu alloys were improved by additives and that the thermal conductivity, machinability, and biocompatibility of the Ag-Cu alloys were improved by Mg addition.

Essential Oil of Pinus koraiensis Exerts Antiobesic and Hypolipidemic Activity via Inhibition of Peroxisome Proliferator-Activated Receptors Gamma Signaling.

Our group previously reported that essential oil of Pinus koraiensis (EOPK) exerts antihyperlipidemic effects via upregulation of low-density lipoprotein receptor and inhibition of acyl-coenzyme A. In the present study, we investigated the antiobesity and hypolipidemic mechanism of EOPK using in vitro 3T3-L1 cells and in vivo HFD-fed rats. EOPK markedly suppressed fat accumulation and intracellular triglyceride associated with downregulation of adipogenic transcription factor expression, including PPAR γ and CEBP α in the differentiated 3T3-L1 adipocytes. Additionally, EOPK attenuated the expression levels of FABP and GPDH as target genes of PPAR γ during adipocyte differentiation. Furthermore, PPAR γ inhibitor GW9662 enhanced the decreased expression of FABP and PPAR γ and fat accumulation induced by EOPK. To confirm the in vitro activity of EOPK, animal study was performed by administering normal diet, HFD, and/or EOPK at the dose of 100 or 200 mg/kg for 6 weeks. Consistently, EOPK significantly suppressed body weight gain, serum triglyceride, total cholesterol, LDL cholesterol, and AI value and increased HDL cholesterol in a dose-dependent manner. Immunohistochemistry revealed that EOPK treatment abrogated the expression of PPAR γ in the liver tissue sections of EOPK-treated rats. Taken together, our findings suggest that EOPK has the antiobesic and hypolipidemic potential via inhibition of PPAR γ -related signaling.

Anti-inflammatory cycloartane-type saponins of Astragalus membranaceus.

A new cycloartane-type triterpene glycoside, agroastragaloside V (1) was isolated from the roots of Astragalus membranaceus. The structure was identified as 3-O-ß-(2'-O-acetyl)-D-xylopyranosyl-6-O-ß-D-glucopyranosyl-(24S)-3ß,6α,24α,25-tetrahydroxy- 9,19-cyclolanostane, by means of spectroscopic methods, including HR-FAB/MS, 1D NMR (1H, 13C, DEPT), 2D NMR (gCOSY, gHSQC, gHMBC, NOESY), and IR spectroscopy. Four known cycloartane glycosides, namely, agroastragaloside I (2), agroastragaloside II (3), isoastragaloside II (4) and astragaloside IV (5) were also isolated. All isolated compounds were tested for the ability to inhibit LPS-induced nitric oxide production in RAW264.7 macrophages.

Inhibition of Connexin 26/43 and Extracellular-Regulated Kinase Protein Plays a Critical Role in Melatonin Facilitated Gap Junctional Intercellular Communication in Hydrogen Peroxide-Treated HaCaT Keratinocyte Cells.

Though melatonin was known to regulate gap junctional intercellular communication (GJIC) in chick astrocytes and mouse hepatocytes, the underlying mechanism by melatonin was not elucidated in hydrogen peroxide- (H(2)O(2)-) treated HaCaT keratinocyte cells until now. In the current study, though melatonin at 2 mM and hydrogen peroxide (H(2)O(2)) at 300 µM showed weak cytotoxicity in HaCaT keratinocyte cells, melatonin significantly suppressed the formation of reactive oxygen species (ROS) in H(2)O(2)-treated HaCaT cells compared to untreated controls. Also, the scrape-loading dye-transfer assay revealed that melatonin enhances the intercellular communication by introducing Lucifer Yellow into H(2)O(2)-treated cells. Furthermore, melatonin significantly enhanced the expression of connexin 26 (Cx26) and connexin 43 (Cx43) at mRNA and protein levels, but not that of connexin 30 (Cx30) in H(2)O(2)-treated HaCaT cells. Of note, melatonin attenuated the phosphorylation of extracellular signal-regulated protein kinases (ERKs) more than p38 MAPK or JNK in H(2)O(2)-treated HaCaT cells. Conversely, ERK inhibitor PD98059 promoted the intercellular communication in H(2)O(2)-treated HaCaT cells. Furthermore, combined treatment of melatonin (200 µM) and vitamin C (10 µg/mL) significantly reduced ROS production in H(2)O(2)-treated HaCaT cells. Overall, these findings support the scientific evidences that melatonin facilitates gap junctional intercellular communication in H(2)O(2)-treated HaCaT keratinocyte cells via inhibition of connexin 26/43 and ERK as a potent chemopreventive agent.

Efficacy and tolerability of diphenyl-dimethyl-dicarboxylate plus garlic oil in patients with chronic hepatitis.

OBJECTIVE: To investigate the hepatoprotective effect, safety and tolerability of oral preparation comprising dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB) plus garlic oil (GO) in chronic hepatitis patients. METHODS: In this double-blind, placebo-controlled clinical trial conducted for 6 weeks with 1-week follow-up, a total of 88 patients with histologically confirmed chronic hepatitis and persistently elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were enrolled and randomly assigned to one of 4 treatment groups: placebo (Group A) and 3 escalating dose groups (2, 3, or 6 study drug capsules a day) (Groups B - D). Each study drug capsule contains 25 mg DDB plus 50 mg GO. Efficacy was assessed by monitoring changes in the circulating activities of ALT and AST as surrogate markers for liver injury. Safety and tolerability were assessed based on the evaluation of clinically adverse events and laboratory test results. RESULTS: Of 88 patients, 83 took at least one dose of study drug and 79 completed the study without any protocol violation. The majority of patients (81/83, 98%) had been infected with HBV. The proportions of patients whose ALT levels returned to normal ranges at Week 6, a primary outcome, were significantly different among 4 groups: 16% (3/19), 41% (9/22), 52% (11/21), and 88% (15/17) in Groups A, B, C, and D, respectively (p < 0.001). The proportions were significantly higher in Groups C (p = 0.022) and D (p < 0.001) but not in Group B compared to Group A. Interestingly, the proportion of Group D was higher than that of Group C (p = 0.034), suggesting a dose-response effect of DDB plus GO on the decrease of ALT levels. The mean ALT levels started to decrease from Week 1 in patients treated with DDB plus GO, whereas no decrease was seen in placebo group. The mean AST levels had a decreasing trend in all doses of DDB plus GO groups. Notably, patients treated with 6 capsules of DDB plus GO daily exhibited the statistically significant decrease in AST levels from Week 3. However, there was no difference in the proportions of patients with the AST decrease to normal ranges after 6-week therapy among 4 groups. The effects of DDB plus GO on decreases in ALT and AST levels lasted until 1 week after completion of treatment. Additionally, the ratios of ALT to AST gradually decreased in patients treated with DDB plus GO over time, suggesting higher degrees of reduction in ALT than in AST in those groups. No clinically meaningful adverse events and laboratory abnormalities were observed during the study period. CONCLUSIONS: The 6-week treatment of DDB plus GO lowered serum aminotransferase activities in patients with chronic hepatitis induced by HBV and/or HCV and was well tolerated. For the treatment of viral hepatitis patients, the optimal dose of this preparation was 3 to 6 capsules per day.