Mobility and current boosting of In-Ga-Zn-O thin-film transistors with metal capping layer oxidation.

This study investigates the effect of an oxidized Ta capping layer on the boosting of field-effect mobility (µFE) of amorphous In-Ga-Zn-O (a-IGZO) Thin-film transistors (TFTs). The oxidation of Ta creates additional oxygen vacancies on the a-IGZO channel surface, leading to increased carrier density. We investigate the effect of increasing Ta coverage on threshold voltage (Vth), on-state current,µFEand gate bias stress stability of a-IGZO TFTs. A significant increase inµFEof over 8 fold, from 16 cm2Vs-1to 140 cm2Vs-1, was demonstrated with the Ta capping layer covering 90% of the channel surface. By partial leaving the a-IGZO uncovered at the contact region, a potential barrier region was created, maintaining the low off-state current and keeping the threshold voltage near 0 V, while the capped region operated as a carrier-boosted region, enhancing channel conduction. The results reported in this study present a novel methodology for realizing high-performance oxide semiconductor devices. The demonstrated approach holds promise for a wide range of next-generation device applications, offering new avenues for advancement in metal oxide semiconductor TFTs.

Improved high voltage operation of amorphous In-Ga-Zn-O thin film transistor by carrier density enhancement.

We report on improved high voltage operation of amorphous-In-Ga-Zn-O (a-IGZO) thin film transistors (TFTs) by increasing carrier density and distributing the high bias field over the length of the device which utilizes an off-set drain structure. By decreasing the O2partial pressure during sputter deposition of IGZO, the channel carrier density of the high voltage a-IGZO TFT (HiVIT) was increased to ∼1018cm-3. Which reduced channel resistance and therefore the voltage drop in the ungated offset region during the on-state. To further decrease the electric field in the offset region, we applied Ta capping and subsequent oxidation to locally increase the oxygen vacancy levels in the offset region thereby increasing local carrier density. The reduction of the drain field in the offset region from 1.90 Vµm-1to 1.46 Vµm-1at 200 V drain voltage, significantly improved the operational stability of the device by reducing high field degradation. At an extreme drain voltage of 500 V, the device showed an off-state current of ∼10-11A and on-state current of ∼1.59 mA demonstrating that with further enhancements the HiVIT may be applicable to thin-film form, low leakage, high voltage control applications.

Chemomechanical Properties and Biocompatibility of Various Premixed Putty-type Bioactive Ceramic Cements.

INTRODUCTION: This study aimed to evaluate the chemomechanical properties and biocompatibility of recently introduced premixed putty-type bioactive ceramic cements (PPBCs). METHODS: Including ProRoot MTA (PMTA) as a control, BC RRM fast-set putty (BCPT), Well-Root PT (WRPT), One-Fil PT (OFPT), and Endocem MTA premixed (ECPM) were compared to evaluate setting time, radiopacity, pH change, and microhardness. Biocompatibility on human dental pulp cells was compared using CCK-8 assay. Mineralization potential was evaluated using alkaline phosphatase activity, Alizarin Red S (ARS) staining, and quantitative real-time polymerase chain reaction with odontogenic gene marker. For data analysis, 1-way analysis of variance and Tukey's post hoc test were used at the significance level of 95%. RESULTS: Among the PPBCs, BCPT presented the longest (552 ± 27) setting time (minutes) and others showed significantly shorter time than PMTA (334 ± 22) (P < .05). WRPT (6.20 ± 0.54) and OFPT (5.82 ± 0.50) showed significantly higher radiopacity values (mmAl) and others showed similar value compared with PMTA (P > .05). All PPBCs showed high alkaline pH from fresh materials and tended to increase according to time periods from 30 minutes to 12 hours. ECPM showed the highest value of microhardness (81.62 ± 5.90), WRPT showed similar, and others showed lower than PMTA (P < .05). All PPBCs showed biocompatibility in CCK-8 assay. All PPBCs showed similar or better value compared with PMTA in ALP and ARS staining, and ALP and DSPP marker expression (P < .05). CONCLUSIONS: The PPBCs showed clinically acceptable chemomechanical properties and favorable mineralization potential.

Influence of bridge structure manipulation on the electrochemical performance of π-conjugated molecule-bridged silicon quantum dot nanocomposite anode materials for lithium-ion batteries.

To assess the influence of bridge structure manipulation on the electrochemical performance of π-conjugated molecule-bridged silicon quantum dot (Si QD) nanocomposite (SQNC) anode materials, we prepared two types of SQNCs by Sonogashira cross-coupling and hydrosilylation reactions; one is SQNC-VPEPV, wherein the Si QDs are covalently bonded by vinylene (V)-phenylene (P)-ethynylene (E)-phenylene-vinylene, and the other is SQNC-VPV. By comparing the electrochemical performances of the SQNCs, including that of the previously reported SQNC-VPEPEPV, we found that the SQNC with the highest specific capacity varied depending on the applied current density; SQNC-VPEPV (1420 mA h g-1) > SQNC-VPV (779 mA h g-1) > SQNC-VPEPEPV(465 mA h g-1) at 800 mA g-1, and SQNC-VPV (529 mA h g-1) > SQNC-VPEPEPV (53 mA h g-1) > SQNC-VPEPV (7 mA h g-1) at 2000 mA g-1. To understand this result, we performed EIS and GITT measurements of the SQNCs. In the course of investigating the lithium-ion diffusion coefficient, charge/discharge kinetics, and electrochemical performance of the SQNC anode materials, we found that electronic conductivity is a key parameter for determining the electrochemical performance of the SQNC. Two probable causes for the unique behavior of the electrochemical performances of the SQNCs are anticipated: (i) the SQNC with predominant electronic conductivity is varied depending on the current density applied during the cell operation, and (ii) the degree of surface oxidation of the Si QDs in the SQNCs varies depending on the structures of the surface organic molecules of the Si QDs and the bridging molecules of the SQNCs. Therefore, differences in the amount of oxides (SiO2)/suboxides (SiOx) on the surface of Si QDs lead to significant differences in conductivity and electrochemical performance between the SQNCs.

Classical monocyte-derived macrophages as therapeutic targets of umbilical cord mesenchymal stem cells: comparison of intratracheal and intravenous administration in a mouse model of pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that has no cure. Although mesenchymal stem cells (MSCs) have been reported to ameliorate lung inflammation and fibrosis in mouse models, their mechanisms of action remain unknown. Therefore, we aimed to determine the changes in various immune cells, especially macrophages and monocytes, involved in the effects of MSC treatment on pulmonary fibrosis. METHODS: We collected and analyzed explanted lung tissues and blood from patients with IPF who underwent lung transplantation. After establishing a pulmonary fibrosis model via the intratracheal administration of bleomycin (BLM) to 8-week-old mice, MSCs derived from human umbilical cords were administered intravenously or intratracheally on day 10 and the lungs were immunologically analyzed on days 14 and 21. Flow cytometry was performed to analyze the immune cell characteristics, and gene expression levels were examined using quantitative reverse transcription-polymerase chain reaction. RESULTS: In the histological analysis of explanted human lung tissues, the terminally fibrotic areas contained a larger number of macrophages and monocytes than the early fibrotic areas of the lungs. When human monocyte-derived macrophages (MoMs) were stimulated with interleukin-13 in vitro, the expression of type 2 macrophage (M2) markers was more prominent in MoMs from the classical monocyte subset than in those from intermediate or non-classical monocyte subsets, and MSCs suppressed M2 marker expression independent of MoM subsets. In the mouse model, the increased number of inflammatory cells in the bronchoalveolar lavage fluid and the degree of lung fibrosis observed in BLM-treated mice were significantly reduced by MSC treatment, which tended to be more prominent with intravenous administration than intratracheal administration. Both M1 and M2 MoMs were upregulated in BLM-treated mice. The M2c subset of M2 MoMs was significantly reduced by MSC treatment. Among M2 MoMs, M2 MoMs derived from Ly6C+ monocytes were most effectively regulated by the intravenous administration, not intratracheal administration, of MSCs. CONCLUSIONS: Inflammatory classical monocytes may play a role in lung fibrosis in human IPF and BLM-induced pulmonary fibrosis. Intravenous rather than intratracheal administration of MSCs may ameliorate pulmonary fibrosis by inhibiting monocyte differentiation into M2 macrophages.

Intravenous Mesenchymal Stem Cell Administration Modulates Monocytes/Macrophages and Ameliorates Asthmatic Airway Inflammation in a Murine Asthma Model.

Although asthma is a common chronic airway disease that responds well to anti-inflammatory agents, some patients with asthma are unresponsive to conventional treatment. Mesenchymal stem cells (MSCs) have therapeutic potential for the treatment of inflammatory diseases owing to their immunomodulatory properties. However, the target cells of MSCs are not yet clearly known. This study aimed to determine the effect of human umbilical cord-derived MSCs (hUC-MSCs) on asthmatic lungs by modulating innate immune cells and effector T cells using a murine asthmatic model. Intravenously administered hUC-MSCs reduced airway resistance, mucus production, and inflammation in the murine asthma model. hUC-MSCs attenuated not only T helper (Th) 2 cells and Th17 cells but also augmented regulatory T cells (Tregs). As for innate lymphoid cells (ILC), hUC-MSCs effectively suppressed ILC2s by downregulating master regulators of ILC2s, such as Gata3 and Tcf7. Finally, regarding lung macrophages, hUC-MSCs reduced the total number of macrophages, particularly the proportion of the enhanced monocyte-derived macrophage population. In a closer examination of monocyte-derived macrophages, hUC-MSCs reduced the M2a and M2c populations. In conclusion, hUC-MSCs can be considered as a potential anti- asthmatic treatment given their therapeutic effect on the asthmatic airway inflammation in a murine asthma model by modulating innate immune cells, such as ILC2s, M2a, and M2c macrophages, as well as affecting Tregs and effector T cells.

Mesenchymal Stem Cells Attenuate Asthmatic Inflammation and Airway Remodeling by Modulating Macrophages/Monocytes in the IL-13-Overexpressing Mouse Model.

Mesenchymal stem cells (MSCs) are attractive alternatives to conventional anti-asthmatic drugs for severe asthma. Mechanisms underlying the anti-asthmatic effects of MSCs have not yet been elucidated. This study evaluated the anti-asthmatic effects of intravenously administered MSCs, focusing on macrophages and monocytes. Seven-week-old transgenic (Tg) mice with lung-specific overexpression of IL-13 were used to simulate chronic asthma. MSCs were intravenously administered four days before sampling. We examined changes in immune cell subpopulations, gene expression, and histological phenotypes. IL-13 Tg mice exhibited diverse features of chronic asthma, including severe type 2 inflammation, airway fibrosis, and mucus metaplasia. Intravenous administration of MSCs attenuated these asthmatic features just four days after a single treatment. MSC treatment significantly reduced SiglecF-CD11c-CD11b+ monocyte-derived macrophages (MoMs) and inhibited the polarization of MoMs into M2 macrophages, especially M2a and M2c. Furthermore, MSCs downregulated the excessive accumulation of Ly6c- monocytes in the lungs. While an intravenous adoptive transfer of Ly6c- monocytes promoted the infiltration of MoM and Th2 inflammation, that of MSC-exposed Ly6c- monocytes did not. Ex vivo Ly6c- MoMs upregulated M2-related genes, which were reduced by MSC treatment. Molecules secreted by Ly6c- MoMs from IL-13 Tg mice lungs upregulated the expression of fibrosis-related genes in fibroblasts, which were also suppressed by MSC treatment. In conclusion, intravenously administered MSCs attenuate asthma phenotypes of chronic asthma by modulating macrophages. Identifying M2 macrophage subtypes revealed that exposure to MSCs transforms the phenotype and function of macrophages. We suggest that Ly6c- monocytes could be a therapeutic target for asthma management.

Microelectronic current-sourcing device based on band-to-band tunneling current.

A new stable current-sourcing transistor is developed using the band-to-band tunneling phenomenon. A heterojunction between thin film WS2and heavily hole-doped bulk silicon converts a section of the WS2contacting the silicon into a hole-doped WS2inside the WS2channel, and band-to-band tunneling occurs between the electron-doped and hole-doped WS2. The output current is regulated by the tunneling barrier thickness. The thickness depends on the gate bias for device switching, but is less sensitive to the source bias, enabling stable output currents. The minimum line sensitivity is 2.6%, and the temperature coefficient is 1.4 × 103ppm°C-1. The device can be operated as a current sourcing device with an ultralow output current and power consumption.

Peripheral blood transcriptomic clusters uncovered immune phenotypes of asthma.

BACKGROUND: Transcriptomic analysis has been used to elucidate the complex pathogenesis of heterogeneous disease and may also contribute to identify potential therapeutic targets by delineating the hub genes. This study aimed to investigate whether blood transcriptomic clustering can distinguish clinical and immune phenotypes of asthmatics, and microbiome in asthmatics. METHODS: Transcriptomic expression of peripheral blood mononuclear cells (PBMCs) from 47 asthmatics and 21 non-asthmatics was measured using RNA sequencing. A hierarchical clustering algorithm was used to classify asthmatics. Differentially expressed genes, clinical phenotypes, immune phenotypes, and microbiome of each transcriptomic cluster were assessed. RESULTS: In asthmatics, three distinct transcriptomic clusters with numerously different transcriptomic expressions were identified. The proportion of severe asthmatics was highest in cluster 3 as 73.3%, followed by cluster 2 (45.5%) and cluster 1 (28.6%). While cluster 1 represented clinically non-severe T2 asthma, cluster 3 tended to include severe non-T2 asthma. Cluster 2 had features of both T2 and non-T2 asthmatics characterized by the highest serum IgE level and neutrophil-dominant sputum cell population. Compared to non-asthmatics, cluster 1 showed higher CCL23 and IL1RL1 expression while the expression of TREML4 was suppressed in cluster 3. CTSD and ALDH2 showed a significant positive linear relationship across three clusters in the order of cluster 1 to 3. No significant differences in the diversities of lung and gut microbiomes were observed among transcriptomic clusters of asthmatics and non-asthmatics. However, our study has limitations in that small sample size data were analyzed with unmeasured confounding factors and causal relationships or function pathways were not verified. CONCLUSIONS: Genetic clustering based on the blood transcriptome may provide novel immunological insight, which can be biomarkers of asthma immune phenotypes. Trial registration Retrospectively registered.

Intratracheal administration of mesenchymal stem cells modulates lung macrophage polarization and exerts anti-asthmatic effects.

Mesenchymal stem cells (MSCs) possess immunomodulatory properties that have therapeutic potential for the treatment of inflammatory diseases. This study investigates the effects of direct MSC administration on asthmatic airways. Umbilical cord MSCs (ucMSCs) were intratracheally administered to six-week-old female BALB/c mice sensitized and challenged with ovalbumin; airway hyperresponsiveness (AHR), analyses of airway inflammatory cells, lung histology, flow cytometry, and quantitative real-time PCR were performed. Furthermore, ex vivo and in vitro experiments were performed to assess the effects of ucMSC on M2 activation. Intratracheally administered ucMSCs decreased degree of airway resistance and the number of inflammatory cells such as T helper 2 (Th2) cells, type 2 innate lymphoid cells (ILC2), and macrophages in the murine asthma model. Particularly, MHCII and CD86 expression diminished in dendritic cells and alveolar macrophages (AMs) following ucMSC treatment. SiglecF+CD11c+CD11b- AMs show a negative correlation with type II inflammatory cells including Th2 cells, ILC2, and eosinophils in asthmatic mice and were restored following intratracheal ucMSCs treatment. In addition, ucMSCs decreased the macrophage polarization to M2, particularly M2a. The expression levels of markers associated with M2 polarization and Th2 inflammation were also decreased. ucMSC reduced Il-12 and Tnfa expression as well as that of M2 markers such as Cd206 and Retnla ex vivo. Furthermore, the in vitro study using IL-4 treated macrophages confirmed that both direct and indirect MSC treatment significantly reduced the expression of Il-5 and Il-13. In conclusion, ucMSCs appear to suppress type II inflammation by regulating lung macrophages via soluble mediators.

Mesenchymal stem cells exert their anti-asthmatic effects through macrophage modulation in a murine chronic asthma model.

Despite numerous previous studies, the full action mechanism of the pathogenesis of asthma remains undiscovered, and the need for further investigation is increasing in order to identify more effective target molecules. Recent attempts to develop more efficacious treatments for asthma have incorporated mesenchymal stem cell (MSC)-based cell therapies. This study aimed to evaluate the anti-asthmatic effects of MSCs primed with Liproxstatin-1, a potent ferroptosis inhibitor. In addition, we sought to examine the changes within macrophage populations and their characteristics in asthmatic conditions. Seven-week-old transgenic mice, constitutively overexpressing lung-specific interleukin (IL)-13, were used to simulate chronic asthma. Human umbilical cord-derived MSCs (hUC-MSCs) primed with Liproxstatin-1 were intratracheally administered four days prior to sampling. IL-13 transgenic mice demonstrated phenotypes of chronic asthma, including severe inflammation, goblet cell hyperplasia, and subepithelial fibrosis. Ly6C+M2 macrophages, found within the pro-inflammatory CD11c+CD11b+ macrophages, were upregulated and showed a strong correlation with lung eosinophil counts. Liproxstatin-1-primed hUC-MSCs showed enhanced ability to downregulate the activation of T helper type 2 cells compared to naïve MSCs in vitro and reduced airway inflammation, particularly Ly6C+M2 macrophages population, and fibrosis in vivo. In conclusion, intratracheal administration is an effective method of MSC delivery, and macrophages hold great potential as an additional therapeutic target for asthma.

An Ultralow Power Mixed Dimensional Heterojunction Transistor Based on the Charge Plasma pn Junction.

Development of a reliable doping method for 2D materials is a key issue to adopt the materials in the future microelectronic circuits and to replace the silicon, keeping the Moore's law toward the sub-10 nm channel length. Especially hole doping is highly required, because most of the transition metal dichalcogenides (TMDC) among the 2D materials are electron-doped by sulfur vacancies in their atomic structures. Here, hole doping of a TMDC, tungsten disulfide (WS2 ) using the silicon substrate as the dopant medium is demonstrated. An ultralow-power current sourcing transistor or a gated WS2 pn diode is fabricated based on a charge plasma pn heterojunction formed between the WS2 thin-film and heavily doped bulk silicon. An ultralow switchable output current down to 0.01 nA µm-1 , an off-state current of ≈1 × 10-14 A µm-1 , a static power consumption range of 1 fW µm-1 -1 pW µm-1 , and an output current ratio of 103 at 0.1 V supply voltage are achieved. The charge plasma heterojunction allows a stable (less than 3% variation) output current regardless of the gate voltage once it is turned on.

Anti-Obesity Effect of Porcine Collagen Peptide in 3T3-L1 Adipocytes and High-Fat Diet-Fed Mice by Regulating Adipogenesis.

Obesity is one of the most common diseases caused by an imbalance in the intake and expenditure of energy, and it is associated with various metabolic complications. This study aimed at investigating the anti-obesity effects and mechanisms of porcine collagen peptide (PCP) using 3T3-L1 preadipocytes and high-fat diet (HFD)-fed mice. The PCP treatment significantly inhibited the adipocyte differentiation and attenuated the mRNA expression of transcription factors (CCAAT/enhancer-binding protein alpha [C/EBPα] and peroxisome proliferator-activated receptor gamma [PPARγ]) and the lipogenic gene (fatty acid synthase [FAS]) expression in 3T3-L1 preadipocytes. In the in vivo study, HFD-fed mice were fed low- (1.5 g/kg body weight/day) and high- (4.5 g/kg body weight/day) PCP for 12 weeks and compared with the normal diet-fed group and HFD-fed control group. The PCP-fed groups showed significantly lower body weight gain, white fat weight gain, serum triglycerides, and adipocyte size compared with the HFD-fed group. The changes in body fat were associated with the upregulation of adiponectin and the downregulation of leptin, C/EBPα, PPARγ, and FAS. These results suggest that PCP has the potential to reduce obesity by suppressing adipogenesis and could be applied as a functional food material.

Effect of Acinetobacter lwoffii on the modulation of macrophage activation and asthmatic inflammation.

BACKGROUND: Although lung macrophages are directly exposed to external stimuli, their exact immunologic roles in asthma are still largely unknown. The aim of this study was to investigate the anti-asthmatic effect of Acinetobacter lwoffii in terms of lung macrophage modulation. METHODS: Six-week-old female BALB/c mice were sensitized and challenged with ovalbumin (OVA) with or without intranasal administration of A. lwoffii during the sensitization period. Airway hyperresponsiveness and inflammation were evaluated. Using flow cytometry, macrophages were subclassified according to their activation status. In the in vitro study, a murine alveolar macrophage cell line (MH-S) treated with or without A. lwoffii before IL-13 stimulation were analysed by quantitative RT-PCR. RESULTS: In a murine asthma model, the number of inflammatory cells, including macrophages and eosinophils, decreased in mice treated with A. lwoffii (A. lwoffii/OVA group) compared with untreated mice (OVA group). The enhanced expression of MHCII in macrophages in the OVA group was decreased by A. lwoffii treatment. M2 macrophage subtypes were significantly altered. A. lwoffii treatment decreased CD11b+ M2a and CD11b+ M2c macrophages, which showed strong positive correlations with Th2 cells, ILC2 and eosinophils. In contrast, CD11b+ M2b macrophages were significantly increased by A. lwoffii treatment and showed strong positive correlations with ILC1 and ILC3. In vitro, A. lwoffii down-regulated the expression of M2 markers related but up-regulated those related to M2b macrophages. CONCLUSIONS AND CLINICAL RELEVANCE: Intranasal A. lwoffii exposure suppresses asthma development by suppressing the type 2 response via modulating lung macrophage activation, shifting M2a and M2c macrophages to M2b macrophages.

Graphene surface contacts of tin disulfide transistors for switching performance improvement and contact resistance reduction.

We investigated the performance improvement of tin disulfide channel transistors by graphene contact configurations. From its two-dimensional nature, graphene can make electric contacts only at the outermost layers of the channel. For intralayer current flow, two graphene flakes are contacted at the channel's top or bottom layer. For interlayer current flow, one flake is contacted at the top and bottom of each layer. We compared the transistor performance in terms of current magnitude, mobility, and subthreshold swing between the configurations. From such observations, we deduced that device characteristics depend on resistivity or doping level of individual graphene flakes. We also found that interlayer flow excels in the on-current magnitude and the mobility, and that top-contact configuration excels in the subthreshold swing.

Cell cycle-dependent SUMO-1 conjugation to nuclear mitotic apparatus protein (NuMA).

Covalent conjugation of proteins with small ubiquitin-like modifier 1 (SUMO-1) plays a critical role in a variety of cellular functions including cell cycle control, replication, and transcriptional regulation. Nuclear mitotic apparatus protein (NuMA) localizes to spindle poles during mitosis, and is an essential component in the formation and maintenance of mitotic spindle poles. Here we show that NuMA is a target for covalent conjugation to SUMO-1. We find that the lysine 1766 residue is the primary NuMA acceptor site for SUMO-1 conjugation. Interestingly, SUMO modification of endogenous NuMA occurs at the entry into mitosis and this modification is reversed after exiting from mitosis. Knockdown of Ubc9 or forced expression of SENP1 results in impairment of the localization of NuMA to mitotic spindle poles during mitosis. The SUMOylation-deficient NuMA mutant is defective in microtubule bundling, and multiple spindles are induced during mitosis. The mitosis-dependent dynamic SUMO-1 modification of NuMA might contribute to NuMA-mediated formation and maintenance of mitotic spindle poles during mitosis.

Anti-angiogenic effects of water extract of a formula consisting of Pulsatilla koreana, Panax ginseng and Glycyrrhiza uralensis.

OBJECTIVE: This study aimed to investigate the anti-angiogenic effects of the water extract of Pulsatilla koreana (Yabe ex Nakai) Nakai ex T. Mori., Panax ginseng C.A. Meyer and Glycyrrhiza uralensis Fisch (WEPPG). METHODS: The effects of WEPPG on fibroblast growth factor (bFGF)-induced angiogenesis were evaluated by human umbilical vein endothelial cell (HUVEC) proliferation, adhesion, and migration assays. Capillary tube formation of HUVECs and bFGF-induced chick chorioallantoic membrane (CAM) angiogenesis were also observed. WEPPG was used to treat the HUVECs and CAMs, and then various activities such as proliferation, adhesion, migration, capillary tube formation and cell cycle proteins were analyzed. RESULTS: WEPPG significantly inhibited bFGF-induced HUVEC proliferation, adhesion, migration, and capillary tube formation. Signaling protein analysis showed up-regulated expressions of various proteins including cyclin A, p63 and KIP2 and down-regulated expressions of nibrin and focal adhesion kinase. The blood vessel formation in a CAM treated with WEPPG was markedly reduced compared with the control group. CONCLUSION: These results suggested that the inhibition of angiogenesis by WEPPG can be an action mechanism for its anti-cancer effects.

Pharmacoproteomic analysis of a novel cell-permeable peptide inhibitor of tumor-induced angiogenesis.

P11, a novel peptide ligand containing a PDZ-binding motif (Ser-Asp-Val) with high affinity to integrin α(v)ß(3) was identified from a hexapeptide library (PS-SPCL) using a protein microarray chip-based screening system. Here, we investigated the inhibitory mechanism of P11 (HSDVHK) on tumor-induced angiogenesis via a pharmacoproteomic approach. P11 was rapidly internalized by, human umbilical vein endothelial cells (HUVECs) via an integrin α(v)ß(3)-mediated event. Caveolin and clathrin appeared to be involved in the P11 uptake process. The cell-penetrating P11 resulted in suppression of bFGF-induced HUVEC proliferation in a dose-dependent manner. Phosphorylation of extracellular-signal regulated kinase (ERK1/2) and mitogen-activated protein kinase kinase (MEK) in bFGF-stimulated HUVECs was inhibited by cell-permeable P11. Proteomic analysis via antibody microarray showed up-regulation of p53 in P11-treated HUVECs, resulting in induction of apoptosis via activation of caspases-3, -8, and -9. Several lines of experimental evidence strongly suggest that the molecular mechanism of P11, a novel anti-angiogenic agent, inhibits bFGF-induced HUVEC proliferation via mitogen-activated protein kinase kinase and extracellular-signal regulated kinase inhibition as well as p53-mediated apoptosis related with activation of caspases.

Anti-angiogenic effects of the water extract of HangAmDan (WEHAD), a Korean traditional medicine.

We investigated the anti-angiogenic effects of the water extract of HangAmDan (WEHAD), which is a crude extract of nine Korean medicinal substances of animal and plant origin. In human umbilical vein endothelial cells, WEHAD significantly inhibited bFGF-induced proliferation, adhesion, migration, and capillary tube formation. We used an antibody array to perform an analysis of signaling proteins, which showed up-regulated expression of various proteins including RAD51, RAD52, and p73, and down-regulated expression of pFAK. Blood vessel formation in a chick chorioallantoic membrane (CAM) treated with WEHAD was markedly reduced in length compared with a PBS-treated control group. These results suggest that inhibition of angiogenesis by WEHAD may be the mechanism of action for the anti-cancer effects of HAD.