Oxidative tryptamine dimers from Corynebacterium durum directly target survivin to induce AIF-mediated apoptosis in cancer cells.

Accumulating evidence indicates that microbial communities in the human body crucially affect health through the production of chemical messengers. However, the relationship between human microbiota and cancer has been underexplored. As a result of a biochemical investigation of the commensal oral microbe, Corynebacterium durum, we identified the non-enzymatic transformation of tryptamine into an anticancer compound, durumamide A (1). The structure of 1 was determined using LC-MS and NMR data analysis as bis(indolyl)glyoxylamide, which was confirmed using one-pot synthesis and X-ray crystallographic analysis, suggesting that 1 is an oxidative dimer of tryptamine. Compound 1 displayed cytotoxic activity against various cancer cell lines with IC50 values ranging from 25 to 35 µM. A drug affinity responsive target stability assay revealed that survivin is the direct target protein responsible for the anticancer effect of 1, which subsequently induces apoptosis-inducing factor (AIF)-mediated apoptosis. Inspired by the chemical structure and bioactivity of 1, a new derivative, durumamide B (2), was synthesized using another indole-based neurotransmitter, serotonin. The anticancer properties of 2 were similar to those of 1; however, it was less active. These findings reinforce the notion of human microbiota-host interplay by showing that 1 is naturally produced from the human microbial metabolite, tryptamine, which protects the host against cancer.

Randomized, multicenter, parallel, open, phase 4 study to compare the efficacy and safety of rosuvastatin/amlodipine polypill versus atorvastatin/amlodipine polypill in hypertension patient with dyslipidemia.

The authors performed this study to investigate the efficacy and safety of a rosuvastatin (RSV)/amlodipine (AML) polypill compared with those of atorvastatin (ATV)/AML polypill. We included 259 patients from 21 institutions in Korea. Patients were randomly assigned to 1 of 3 treatment groups: RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, or ATV 20 mg /AML 5 mg. The primary endpoint was the efficacy of the RSV 10.20 mg/AML 5 mg via percentage changes in LDL-C after 8 weeks of treatment, compared with the ATV 20 mg /AML 5 mg. There was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 10 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (full analysis set [FAS]: -7.08%, 95% CI: -11.79 to -2.38, p = .0034, per-protocol analysis set [PPS]: -6.97%, 95% CI: -11.76 to -2.19, p = .0046). Also, there was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 20 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (FAS: -10.13%, 95% CI: -15.41 to -4.84, p = .0002, PPS: -10.96%, 95% CI: -15.98 to -5.93, p < .0001). There was no significant difference in the adverse events rates between RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, and ATV 20 mg/AML 5 mg. In conclusion, while maintaining safety, RSV 10 mg/AML 5 mg and the RSV 20 mg/AML 5 mg more effectively reduced LDL-C compared with the ATV 20 mg /AML 5 mg (Clinical trial: NCT03951207).

Association of height loss and cardiovascular disease: Data from a large Korean cohort.

Background: Height declines with age, and its degree differs among individuals. Despite epidemiologic evidence for the inverse relationship between adult height and cardiovascular disease (CVD) incidence, the clinical significance of height loss in CVD remains to be elucidated. Therefore, this study investigated the association between height loss and CVD incidence. Methods: In total, 127,573 Korean participants were enrolled; their heights were monitored from 2002 to 2011. The annual height loss (cm/year) was the difference between the first and last height measurements within the observation period divided by the number of years. The participants were classified as Group 1 (height loss: <0.3 cm/year; n = 102,554), Group 2 (height loss: 0.3- < 0.6 cm/year; n = 17,324), or Group 3 (height loss: ≥0.6 cm/year; n = 7,695). Results: The cumulative major adverse cardiac and cerebral event (MACCE: cardiac death, non-fatal myocardial infarction, and unplanned hospitalization for heart failure or stroke) incidence rate was 3.6% for Group 1, 4.5% for Group 2, and 5.2% for Group 3. Group 2 (hazard ratio [HR] = 1.27, 95% confidence interval [CI] = 1.17-1.37) and Group 3 (HR = 1.46, 95% CI = 1.32-1.62) had a significantly higher incidence of MACCE than Group 1. In the model adjusted for age, sex, comorbidities, income level, body mass index, smoking, and drinking status, the MACCE risk was higher in Group 2 (HR = 1.11, 95% CI = 1.07-1.20) and Group 3 (HR = 1.25, 95% CI = 1.13-1.39) than in Group 1. Conclusion: The degree of height loss was independently associated with CVD occurrences in the Korean population.

Real-World Treatment Selection Factors and 7-Year Clinical Outcomes between Percutaneous Coronary Intervention and Coronary Artery Bypass Graft Surgery in Left Main Disease.

BACKGROUND: The decision-making factors and long-term clinical outcomes between PCI and CABG in left main (LM) disease are still not well defined in the real world. METHODS: We evaluated consecutive patients (n = 230) with LM disease either treated by PCI (n = 118) or CABG (n = 112). The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, spontaneous myocardial infarction (MI), stroke, and target vessel revascularization (TVR) for 7 years. RESULTS: In the multivariate-adjusted analysis, the presence of intermediate EuroSCORE II and high SYNTAX scores predisposed to CABG. Isolated LM disease was associated with receiving PCI. The PCI group had a similar rate of MACE (HRadj 0.97, 95% CI [0.48-1.94], p = 0.92) and a lower tendency of hard MACE (HRadj 0.49, 95% CI [0.22-1.07], p = 0.07) compared to the CABG group, mainly due to the balance between a higher rate of TVR (HRadj 9.71, p = 0.02) and a lower rate of stroke (HRadj 0.22, p = 0.09) with the PCI group than in the CABG group. CONCLUSIONS: The decision making of treatment strategy was made based on clinical and angiographic factors. The selected patients who received PCI showed similar MACE and trend of a lower rate of composite hard endpoints despite multivariate adjustment.

A retrospective comparison of 3 approaches of vestibuloplasty around mandibular molar implants: apically positioned flap versus free gingival graft versus modified periosteal fenestration.

PURPOSE: This study aimed to clinically evaluate the efficacy of vestibuloplasty around lower molar implants using 3 different modalities: apically positioned flap alone (APF), APF with a free gingival graft (FGG), and APF with modified periosteal fenestration (mPF). METHODS: Three different vestibuloplasty procedures during second-stage implant surgery were performed at the mandibular molar area in 61 patients with a shallow vestibule and insufficient keratinized tissue (KT). The clinical measurements of KT width were recorded at baseline, immediately after surgery (T0), 6 months after surgery (T6), and 12 months after surgery (T12). Soft tissue esthetic scores were measured. RESULTS: An additional KT width gain from baseline to T12 of approximately 2 mm was obtained with FGG and mPF compared to that with APF. Shrinkage of the re-established tissue was lower with mPF and FGG than with APF, whereas the esthetic profile was better with APF and mPF than with FGG. CONCLUSIONS: Within the limitations of this study, mPF showed potential as a promising approach for vestibuloplasty around the lower molar implants compared to the traditional APF and FGG.

Nickel-Templated Replacement of Phosphine Substituents in a Tetradentate Bis(amido)bis(phosphine) Ligand.

The replacement of phosphine substituents in nickel-bound PNNP ligands is reported as an alternative method for preparing multidentate phosphine ligands with alkyl substituents. Treatment of the previously reported bis(phosphide) complex {K(THF)x}22Ph[PNNP]Ni (2) with 2 equiv of MeI, iPrI, and 1,3-dibromoethane formed alkyl-substituted complexes 2Ph,2Me[PNNP]Ni (3), 2Ph,2iPr[PNNP]Ni (4), and 2Ph,propylene[PNNP]Ni (5), respectively. The stereoselectivity (racemic vs meso) of these reactions can be controlled by varying the reaction temperature. The racemic mixtures of products with the new alkyl substituents in an anti configuration were favored at lower temperatures, whereas a larger proportion of meso compounds was acquired at higher temperatures. Further treatment of 3 with KH resulted in selective elimination of the remaining phenyl groups rather than the methyl substituents, affording bis(methylphosphide) complex {K(THF)x}22Me[PNNP]Ni (6). Subsequent treatment of 6 with additional MeI formed 4Me[PNNP]Ni (7), in which all four phenyl groups were replaced with methyl substituents. As a proof of concept, demetalation of the ligand from 7 was achieved using aqueous KCN to form a free dimethylphosphine-substituted ligand H24Me[PNNP] (8), and 8 was subsequently coordinated to a different metal, using PdCl2 to form 4Me[PNNP]Pd (9). Unlike the clean elimination of phenyl substituents from 3, the reactions of KH with 4 and 5 exhibited competitive elimination of both alkyl and phenyl substituents and/or attenuated reactivity.

(-)-Loliolide Isolated from Sargassum horneri Abate UVB-Induced Oxidative Damage in Human Dermal Fibroblasts and Subside ECM Degradation.

Ultraviolet (UV) B exposure is a prominent cause of skin aging and a contemporary subject of interest. The effects are progressing through the generation of reactive oxygen species (ROS) that alter cell signaling pathways related to inflammatory responses. The present study evaluates the protective effects of (7aR)-6-hydroxy-4,4,7a-trimethyl-6,7-dihydro-5H-1-benzofuran-2-one (HTT) isolated from the edible brown algae Sargassum horneri against UVB protective effects in human dermal fibroblasts (HDFs). HTT treatment dose-dependently suppressed intracellular ROS generation in HDFs with an IC50 of 62.43 ± 3.22 µM. HTT abated UVB-induced mitochondrial hyperpolarization and apoptotic body formation. Furthermore, UVB-induced activation of key nuclear factor (NF)-κB and mitogen-activated protein kinase signaling proteins were suppressed in HTT treated cells while downregulating pro-inflammatory cytokines (interleukin-1ß, 6, 8, 33 and tumor necrosis factor-α). Moreover, HTT treatment downregulated matrix metalloproteinase1, 2, 3, 8, 9 and 13 that was further confirmed by the inhibition of collagenase and elastase activity. The evidence implies that HTT delivers protective effects against premature skin aging caused by UVB exposure via suppressing inflammatory responses and degradation of extracellular matrix (ECM) components. Extensive research in this regard will raise perspectives for using HTT as an ingredient in UV protective ointments.

The Anti-Oxidative and Anti-Neuroinflammatory Effects of Sargassum horneri by Heme Oxygenase-1 Induction in BV2 and HT22 Cells.

Sargassum horneri is used as a traditional medicinal agent and exhibits various pharmacological effects. In this study, we found that the 70% EtOH extract contained 34.37 ± 0.75 µg/mg fucosterol. We tested the antioxidant activities of the 70% EtOH extracts and their fractions. The CH2Cl2-soluble fraction showed the strongest DPPH and ABTS radical scavenging activities. Next, we evaluated the anti-neuroinflammatory effects of S. horneri on lipopolysaccharide (LPS)-stimulated BV2 cells. Pretreatment with the extract and fractions suppressed LPS-induced production of nitric oxide (NO) in BV2 cells. The 70% EtOH, CH2Cl2-soluble fraction, and water-soluble fraction inhibited the production of prostaglandin E2, interleukin-6, and tumor necrosis factor-α, as well as markedly blocking LPS-induced expression of inducible NO synthase and cyclooxygenase-2 via inactivation of the nuclear factor-kappa B pathway. In addition, the CH2Cl2-soluble fraction showed the most remarkable heme oxygenase (HO)-1 expression effects and increased nuclear erythroid 2-related factor translocation in the nucleus. In HT22 cells, the CH2Cl2-soluble fraction inhibited cell damage and ROS production caused by glutamate via the regulation of HO-1. Therefore, CH2Cl2-soluble fractions of S. horneri can attenuate oxidative action and neuroinflammatory responses via HO-1 induction, demonstrating their potential in the treatment of neuroinflammatory diseases.

UVB protective effects of Sargassum horneri through the regulation of Nrf2 mediated antioxidant mechanism.

The present study aimed to evaluate the protective effect of a methanol extract of Sargassum horneri (SHM), which contains 6-hydroxy-4,4,7a-trimethyl-5,6,7,7a-tetrahydrobenzofuran-2(4H)-one (HTT) and apo-9'-fucoxanthinone, against ultraviolet B (UVB)-induced cellular damage in human keratinocytes and its underlying mechanism. SHM significantly improved cell viability of UVB-exposed human keratinocytes by reducing the generation of intracellular reactive oxygen species (ROS). Moreover, SHM inhibited UVB exposure-induced apoptosis by reducing the formation of apoptotic bodies and the populations of the sub-G1 hypodiploid cells and the early apoptotic cells by modulating the expression of the anti- and pro-apoptotic molecules, Bcl-2 and Bax, respectively. Furthermore, SHM inhibited NF-κB p65 activation by inducing the activation of Nrf2/HO-1 signaling. The cytoprotective and antiapoptotic activities of SHM are abolished by the inhibition of HO-1 signaling. In further study, SHM restored the skin dryness and skin barrier disruption in UVB-exposed human keratinocytes. Based to these results, our study suggests that SHM protects the cells against UVB-induced cellular damages through the Nrf2/HO-1/NF-κB p65 signaling pathway and may be potentially useful for the prevention of UVB-induced skin damage.

Sargassum horneri (Turner) C. Agardh ethanol extract attenuates fine dust-induced inflammatory responses and impaired skin barrier functions in HaCaT keratinocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Sargassum horneri (Turner) C. Agardh is well known in East Asia as an edible brown alga rich in bioactive compounds. It has an ethnopharmacological significance in traditional Chinese medicine to treat inflammatory disorders varying from edema, furuncles, dysuria to cardiovascular diseases. AIM OF THE STUDY: Surge of fine dust (FD), in densely populated areas, have been reported to cause adverse health conditions ranging from respiratory diseases to inflammatory skin disorders. The current study investigates the protective effects of an ethanol extract from S. horneri (SHE) on FD-induced inflammatory responses and impaired skin hydration in HaCaT keratinocytes. MATERIALS AND METHODS: Intracellular reactive oxygen species (ROS) generation was evaluated with the 2',7'-Dichlorofluorescin diacetate (DCFH-DA) stain. Anti-inflammatory properties of SHE in FD-stimulated HaCaT keratinocytes were investigated for the suppression of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) pathways and downregulation of pro-inflammatory cytokines. As a means of studying FD-induced skin barrier disruption and the effects of SHE on stratum corneum hydration-controlling factors, tight junction regulatory mediators, and hyaluronic acid (HA) production were evaluated using keratinocytes. RESULTS: SHE suppressed the intracellular ROS production, simultaneously improving cell viability in FD-stimulated keratinocytes. Also, SHE upregulated anti-inflammatory cytokine interleukin (IL)-4 while downregulating inflammatory cytokines IL-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α; epidermal and epithelial cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP); thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and regulated upon activation, normally T-expressed, and presumably secreted expression and suppressed (RANTES) chemokine, MAPK and NF-κB mediators in a dose-dependent manner. Furthermore, SHE ameliorated filaggrin, involucrin, lymphoepithelial Kazal-type-related inhibitor (LEKTI), signifying its beneficial effects on deteriorated skin hydration caused by FD-induced inflammation. SHE further exhibited its skin protective effects regulating the tight junction proteins; Occludin, zonula occludens (ZO)-1, claudin-1, claudin-4, claudin-7, and claudin-23 while increasing the production of HA minimizing skin damage. CONCLUSIONS: Anti-inflammatory effects of, SHE against FD-induced keratinocyte inflammation is attributable to the suppression of upstream MAPK and NF-κB mediators. SHE indicated potential anti-inflammatory properties attenuating deteriorated skin barrier function in HaCaT keratinocytes. The effects are attributable to the polyphenols and other antioxidant compounds in SHE. Further studies could envisage the use of SHE for developing rejuvenating cosmetics.

Pharmacodynamic Profile and Prevalence of Bleeding Episode in East Asian Patients with Acute Coronary Syndromes Treated with Prasugrel Standard-Dose versus De-escalation Strategy: A Randomized A-MATCH Trial.

Compared with Caucasian patients, East Asian patients have the unique risk-benefit trade-off and different responsiveness to antithrombotic regimens. The aim of this study was to compare pharmacodynamic profile in East Asian patients with acute coronary syndromes (ACSs) treated with prasugrel standard-dose versus a de-escalation strategy. Before discharge, ACS patients with age <75 years or weight ≥60 kg (n = 255) were randomly assigned to the standard-dose (10-mg group) or de-escalation strategy (5-mg group or platelet function test [PFT]-guided group). After 1 month, VerifyNow P2Y12 assay-based platelet reactivity (P2Y12 reaction unit [PRU]) and bleeding episodes were evaluated. Primary endpoint was the percentage of patients with the therapeutic window (85 ≤ PRU ≤ 208). The 250 patients completed 1-month treatment. The percentage of patients within the therapeutic window was significantly lower in the 10-mg group (n = 85) compared with the 5-mg (n = 83) and PFT-guided groups (n = 82) (35.3 vs. 67.5 vs. 65.9%) (odds ratio [OR]: 3.80 and 3.54; 95% confidence interval [CI]: 2.01-7.21 and 1.87-6.69, respectively). Compared with the 10-mg group, the bleeding rate was tended to be lower with de-escalation strategies (35.3 vs. 24.1% vs. 23.2%) (hazard ratio [HR]: 0.58 and 0.55; 95% CI: 0.30-1.14 and 0.28-1.09, respectively). "PRU < 127" was the optimal cut-off for predicting 1-month bleeding events (area under the curve: 0.616; 95% CI: 0.543-0.689; p = 0.005), which criteria was significantly associated with early discontinuation of prasugrel treatment (HR: 2.00; 95% CI: 1.28-3.03; p = 0.001). In conclusion, compared with the standard-dose prasugrel, the prasugrel de-escalation strategy in East Asian patients presented with ACS showed a higher chance within the therapeutic window and a lower tendency toward bleeding episodes. REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier:NCT01951001.

Low molecular weight fucoidan fraction ameliorates inflammation and deterioration of skin barrier in fine-dust stimulated keratinocytes.

Recently evidence linking the effects of fine-dust (FD) on skin inflammation is exaggerating. Fucoidan derived from brown algae has great potential for ameliorating oxidative stress and inflammation. Herein, a fucoidan fraction (SHC4-6) was purified from an enzymatic (Celluclast) extract of an invasive seaweed, Sargassum horneri following gradient ethanol precipitation and anion exchange chromatography. Effectiveness of SHC4-6 in ameliorating FD (from Beijing, China)-induced inflammatory responses in HaCaT keratinocytes and recovery of skin barrier dysfunction was evaluated. SHC4-6 was comprising of sulfated mannofucans with their molecular weights distributed around 45 kDa. SHC4-6 dose-dependently lowered ROS levels in FD-induced HaCaT keratinocytes, ameliorating viability at 50 µg mL-1. SHC4-6 downregulated inflammatory cytokines, tumor necrosis factor-α, interleukin (IL)-1ß, -5, -6, -8, -13, interferon-γ, and chemokines, macrophage-derived chemokine, eotaxin, and thymus and activation regulated chemokine by inhibiting mitogen-activated protein kinase and nuclear factor-κB pathways. SHC4-6 treatment ameliorated key tight junction proteins and skin hydration factors, depicting the effects of fucoidan in reducing FD-induced inflammation and skin barrier deterioration. With further studies in place, SHC4-6 could be used as an ingredient for developing cosmetics to relieve FD-induced skin inflammation.

The Influence of Redox-Innocent Donor Groups in Tetradentate Ligands Derived from o-Phenylenediamine: Electronic Structure Investigations with Nickel.

The continued development of redox-active ligands requires an understanding as to how ligand modifications and related factors affect the locus of redox activity and spin density in metal complexes. Here we describe the synthesis, characterization, and electronic structure of nickel complexes containing triaryl NNNN (1) and SNNS (2) ligands derived from o-phenylenediamine. The tetradentate ligands in 1 and 2 were investigated and compared to those in metal complexes with compositionally similar ligands to determine how ligand-centered redox properties change when redox-active flanking groups are replaced with redox-innocent NMe2 or SMe. A derivative of 2 in which the phenylene backbone was replaced with ethylene (3) was also prepared to interrogate the importance of o-phenylenediamine for ligand-centered redox activity. Cyclic voltammograms collected for 1 and 2 revealed two fully reversible ligand-centered redox events. Remarkably, several quasi-reversible ligand-centered redox waves were also observed for 3 despite the absence of the o-phenylenediamine subunit. Oxidizing 1 and 2 with silver salts containing different counteranions (BF4-, OTf-, NTf2-) allowed the electrochemically generated complexes to be analyzed as a function of different oxidation states using single-crystal X-ray diffraction (XRD), EPR spectroscopy, and S K-edge X-ray absorption spectroscopy. The experimental data are corroborated by DFT calculations, and together, they reveal how the location of unpaired spin density and electronic structure in singly and doubly oxidized salts of 1 and 2 varies depending on the coordinating ability of the counteranions and exogenous ligands such as pyridine.

Improved early risk stratification of patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention using a combination of serum soluble ST2 and NT-proBNP.

BACKGROUND: Although soluble suppression of tumorigenicity 2 (sST2) in serum is known to be associated with ischemic heart disease and heart failure, data regarding its prognostic impact in ST-segment elevation myocardial infarction (STEMI) is limited. We evaluated the prognostic impacts of serum sST2 and other serum biomarkers in STEMI patients undergoing primary percutaneous coronary intervention (PCI). METHODS: Consecutive all 323 patients with STEMI that underwent primary PCI were enrolled. Blood tests and samples were obtained in an emergency room. The primary endpoint was 1-year major adverse cardiovascular and cerebrovascular events (MACCEs), defined as a composite of cardiovascular death, non-fatal MI, non-fatal stroke, and ischemia-driven revascularization. RESULTS: Mean age was 59.1±13.1 years (men 84%). MACCE (20 cardiovascular deaths, 7 non-fatal MI, 4 non-fatal stroke, 7 ischemia-driven revascularizations) occurred in 38 patients (12%). After adjusting for confounding factors, Cox regression analysis revealed that high serum sST2 (>75.8 ng/mL mean value, adjusted hazard ratio 2.098, 95% CI 1.008-4.367, p = 0.048) and high serum NT-proBNP level (>400 pg/mL, adjusted hazard ratio 2.606, 95% CI 1.086-6.257, p = 0.032) at the time of presentation independently predicted MACCE within a year of primary PCI. Furthermore, when high serum sST2 level was combined with high serum NT-proBNP level, the hazard ratio of MACCE was highest (adjusted hazard ratio 7.93, 95% CI 2.97-20.38, p<0.001). CONCLUSION: Elevated serum levels of sST2 or NT-proBNP at the time of presentation were found to predict 1-year MACCE independently and elevated serum levels of sST2 plus NT-proBNP were associated with even poorer prognosis in patients with STEMI undergoing primary PCI.

Increasing injection frequency enhances the survival of injected bone marrow derived mesenchymal stem cells in a critical limb ischemia animal model.

Critical limb ischemia (CLI) is one of the most severe forms of peripheral artery diseases, but current treatment strategies do not guarantee complete recovery of vascular blood flow or reduce the risk of mortality. Recently, human bone marrow derived mesenchymal stem cells (MSCs) have been reported to have a paracrine influence on angiogenesis in several ischemic diseases. However, little evidence is available regarding optimal cell doses and injection frequencies. Thus, the authors undertook this study to investigate the effects of cell dose and injection frequency on cell survival and paracrine effects. MSCs were injected at 106 or 105 per injection (high and low doses) either once (single injection) or once in two consecutive weeks (double injection) into ischemic legs. Mice were sacrificed 4 weeks after first injection. Angiogenic effects were confirmed in vitro and in vivo, and M2 macrophage infiltration into ischemic tissues and rates of limb salvage were documented. MSCs were found to induce angiogenesis through a paracrine effect in vitro, and were found to survive in ischemic muscle for up to 4 weeks dependent on cell dose and injection frequency. In addition, double high dose and low dose of MSC injections increased vessel formation, and decreased fibrosis volumes and apoptotic cell numbers, whereas a single high dose did not. Our results showed MSCs protect against ischemic injury in a paracrine manner, and suggest that increasing injection frequency is more important than MSC dosage for the treatment CLI.

Improvement of Gas-Sensing Performance of Large-Area Tungsten Disulfide Nanosheets by Surface Functionalization.

Semiconducting two-dimensional (2D) transition metal dichalcogenides (TMDCs) are promising gas-sensing materials due to their large surface-to-volume ratio. However, their poor gas-sensing performance resulting from the low response, incomplete recovery, and insufficient selectivity hinders the realization of high-performance 2D TMDC gas sensors. Here, we demonstrate the improvement of gas-sensing performance of large-area tungsten disulfide (WS2) nanosheets through surface functionalization using Ag nanowires (NWs). Large-area WS2 nanosheets were synthesized through atomic layer deposition of WO3 followed by sulfurization. The pristine WS2 gas sensors exhibited a significant response to acetone and NO2 but an incomplete recovery in the case of NO2 sensing. After AgNW functionalization, the WS2 gas sensor showed dramatically improved response (667%) and recovery upon NO2 exposure. Our results establish that the proposed method is a promising strategy to improve 2D TMDC gas sensors.

The role of insulin resistance and metabolic risk factors on culprit coronary plaque.

BACKGROUND: Detailed relationships between insulin resistance (IR) and vulnerable plaque are not clear, therefore, we sought the role of IR and metabolic risk factors on culprit coronary plaque. METHODS: Plaque components at a region of interest (ROI, 10mm) were analyzed by virtual histology intravascular ultrasound. IR was defined as quantitative insulin sensitivity check index (QUICKI) ≤ 0.33. Seven metabolic risk factors (5 risk factors for metabolic syndrome defined by ATP III, history of smoking, and hsCRP) for IR were determined. RESULTS: The data for 150 (males 104) patients were analyzed. Patients with IR (n = 69) had greater necrotic core (NC) at the ROI (21.2 ± 15.8mm(3) vs 15.7 ± 11.9 mm(3), p = 0.02) than in patients without IR (n = 81). The NC at the ROI was correlated with QUICKI (r = -0.16, p = 0.05), HbA1c (r = 0.24, p < 0.01), body mass index (r = 0.17, p = 0.04), presence of diabetes mellitus (r = 0.29, p < 0.001), hsCRP (r = 0.17, p = 0.04) and the numbers of risk factors for IR (r = 0.41, p < 0.001). The multivariate analysis revealed that the numbers of risk factors for IR was an independent factor for the NC at the ROI (beta coefficient = 0.44, p = 0.003), but QUICKI was not (beta coefficient = -0.01, p = 0.94). CONCLUSIONS: Instead of a single measurement of IR index or each metabolic risk factor, clustering of risk factors for IR plays an important role on plaque vulnerability. CONDENSED ABSTRACT: We investigated the role of insulin resistance (IR) on culprit coronary plaque. Patients with IR had a greater amount of necrotic core in culprit coronary lesions than in patients without IR. Rather than a single measurement of IR index or each metabolic risk factor, clustering of metabolic risk factors for IR plays an important role in plaque vulnerability in patients with coronary artery disease. Our study demonstrates the role of IR on culprit coronary plaque and highlights the importance of the clustering of metabolic risk factors for IR in vulnerable plaque pathogenesis.

Ghost in the left ventricle on electrocardiogram-gated cardiac computed tomography by turbulent flow.

We report on an extremely rare case of a fake lesion in the left ventricle on electrocardiogram-gated cardiac computed tomography simulating thrombus or tumor by turbulent flow in a 14-year-old boy. Cardiac magnetic resonance imaging with contrast-enhanced myocardial perfusion and delayed enhancement images were helpful in excluding true thrombus or tumor. Awareness of this potential pitfall is critical in order to avoid unnecessary anticoagulation or surgery.

Association between plasma levels of manganese and periodontal status: a study based on the fourth Korean National Health and Nutrition Examination Survey.

BACKGROUND: This study aims to evaluate the association between plasma levels of manganese (Mn) and periodontal status in a representative sample of Korean adults. METHODS: Plasma levels of Mn and periodontal status were analyzed in 1,679 participants, all of whom were ≥19 years old. Plasma levels of Mn were divided into four quartiles: first (<1.057 µg/dL), second (1.057 to 1.274 µg/dL), third (1.275 to 1.544 µg/dL), and fourth (>1.544 µg/dL). Periodontal status was assessed using the Community Periodontal Index (CPI). Multivariate logistic regression analyses were performed after adjusting for sociodemographic variables, oral and general health behavior, oral health status, and systemic conditions. All analyses took into consideration the complex sampling design, and multivariate analyses were performed in the subgroups. RESULTS: Multivariate logistic regression analyses revealed a significant association between plasma levels of Mn and higher CPI in the total sample. There was a moderate association between first-quartile plasma levels of Mn and higher CPI in males (odds ratio [OR]: 2.13; 95% confidence interval [CI] 1.25 to 3.63) and current smokers (OR: 2.07; 95% CI 1.04 to 4.11), compared to the fourth quartile. CONCLUSION: Periodontal status is significantly associated with plasma levels of Mn in Korean adults, especially in men and smokers.

A randomized, open-label, multicenter trial for the safety and efficacy of adult mesenchymal stem cells after acute myocardial infarction.

Recent studies suggest that the intracoronary administration of bone marrow (BM)-derived mesenchymal stem cells (MSCs) may improve left ventricular function in patients with acute myocardial infarction (AMI). However, there is still argumentative for the safety and efficacy of MSCs in the AMI setting. We thus performed a randomized pilot study to investigate the safety and efficacy of MSCs in patients with AMI. Eighty patients with AMI after successful reperfusion therapy were randomly assigned and received an intracoronary administration of autologous BM-derived MSCs into the infarct related artery at 1 month. During follow-up period, 58 patients completed the trial. The primary endpoint was changes in left ventricular ejection fraction (LVEF) by single-photon emission computed tomography (SPECT) at 6 month. We also evaluated treatment-related adverse events. The absolute improvement in the LVEF by SPECT at 6 month was greater in the BM-derived MSCs group than in the control group (5.9% ± 8.5% vs 1.6% ± 7.0%; P=0.037). There was no treatment-related toxicity during intracoronary administration of MSCs. No significant adverse cardiovascular events occurred during follow-up. In conclusion, the intracoronary infusion of human BM-derived MSCs at 1 month is tolerable and safe with modest improvement in LVEF at 6-month follow-up by SPECT. (ClinicalTrials.gov registration number: NCT01392105).