Universal selective transfer printing via micro-vacuum force.

Transfer printing of inorganic thin-film semiconductors has attracted considerable attention to realize high-performance soft electronics on unusual substrates. However, conventional transfer technologies including elastomeric transfer printing, laser-assisted transfer, and electrostatic transfer still have challenging issues such as stamp reusability, additional adhesives, and device damage. Here, a micro-vacuum assisted selective transfer is reported to assemble micro-sized inorganic semiconductors onto unconventional substrates. 20 µm-sized micro-hole arrays are formed via laser-induced etching technology on a glass substrate. The vacuum controllable module, consisting of a laser-drilled glass and hard-polydimethylsiloxane micro-channels, enables selective modulation of micro-vacuum suction force on microchip arrays. Ultrahigh adhesion switchability of 3.364 × 106, accomplished by pressure control during the micro-vacuum transfer procedure, facilitates the pick-up and release of thin-film semiconductors without additional adhesives and chip damage. Heterogeneous integration of III-V materials and silicon is demonstrated by assembling microchips with diverse shapes and sizes from different mother wafers on the same plane. Multiple selective transfers are implemented by independent pressure control of two separate vacuum channels with a high transfer yield of 98.06%. Finally, flexible micro light-emitting diodes and transistors with uniform electrical/optical properties are fabricated via micro-vacuum assisted selective transfer.

Anti-cancer potential of persimmon (Diospyros kaki) leaves via the PDGFR-Rac-JNK pathway.

Persimmon leaves are known to have some beneficial effects, including ROS elimination, lipid circulation, and neuronal protection. However, their anti-cancer properties and the underlying mechanisms remain unclear. Herein, we show that treatment with the ethanol extract of persimmon, Diospyros kaki, leaves (EEDK) induces cancer cell death and inhibits cell proliferation. Using fluorescence resonance energy transfer (FRET) technology with genetically-encoded biosensors, we first found that EEDK stimulates a PDGFR-Rac signaling cascade in live cells. Moreover, we found that downstream of the PDGFR-Rac pathway, JNKs are activated by EEDK. In contrast, JNK-downstream inhibitors, such as CoCl2, T-5224, and pepstatin A, attenuated EEDK-induced cell death. Thus, we illustrate that the PDGFR-Rac-JNK signaling axis is triggered by EEDK, leading to cancer cell death, suggesting the extract of persimmon leaves may be a promising anti-cancer agent.

Toxicological screening of marine red algae Champia parvula (C. Agardh) against the dengue mosquito vector Aedes aegypti (Linn.) and its non-toxicity against three beneficial aquatic predators.

Larval toxicity of ethanolic extract of C. parvula (Ex-Cp) was prominent in the second and the third instars at the maximum lethal dosage of 100 ppm with 98 and 97 % mortality rate respectively. The LC50 and LC90 was displayed at 43 ppm and 88 ppm dosage respectively. Correspondingly, the sub-lethal dosage (65 ppm) of Ex-Cp significantly alters the carboxylesterase (α and ß), GST and CYP450 enzyme level in both III and IV instar larvae in dose-dependent manner. Similarly, the Ex-Cp displayed significant repellent activity (97 %) with a maximum level of protection time (210 min). Photomicrography assay of Ex-Cp (65 ppm) were toxic to dengue larvae as compared to control. The non-target toxicity of Ex-Cp against the beneficial mosquito predators displayed less toxicity at the maximum dosage of 600 ppm as compared to Temephos. Thus the present research delivers the target and non-target toxicity of red algae C. parvula against the dengue mosquito vector.

The Intraocular Pressure-Lowering Effect of Persimmon leaves (Diospyros kaki) in a Mouse Model of Glaucoma.

The aim of this study was to evaluate the pharmacological efficacy of persimmon leaves in two glaucoma models, microbeads-induced ocular hypertension (OHT) and DBA/2 mouse. Thus, we demonstrated that Ethanol Extract of Diospyros kaki (EEDK) reduced elevated intraocular pressure (IOP) in both mouse models of glaucoma by measurements with a tonometer. In particular, we revealed that retinal ganglion cell loss and optic nerve damage caused by IOP elevation were markedly diminished as assessed by TUNEL assay, H&E staining, and fluorescent staining, while the expression of soluble guanylate cyclase (sGCα-1) increased, when EEDK was administered, as revealed by western blot. Moreover, the b-wave magnitude indicating functional scotopic vision was significantly improved in EEDK-administered DBA/2 mice during the 10-week follow-up study, as observed with electroretinography. Collectively, our results suggested that EEDK could be an effective therapeutic and IOP-lowering agent for preventing and treating retinal degenerative diseases such as glaucoma.

Simultaneous roasting and extraction of green coffee beans by pressurized liquid extraction.

Green coffee extracted by pressurized liquid extraction (PLE) was found to undergo a roasting process similar to traditional roasting. Liquid chromatography-tandem mass spectrometry was used to investigate the chlorogenic acid (CGA) composition and profiling changes by PLE under different extraction conditions and showed almost identical generation and degradation of CGAs occurring during traditional coffee roasting. Compared with the traditional extraction of roasted coffee, optimized PLE coffee showed three- and two-fold higher antioxidant activity and total CGA contents, respectively. Composition diversity and the content of volatile compounds in PLE coffee were found to increase as the PLE temperature increased but were lower than those of traditionally roasted coffee. The sensory attributes of PLE coffee were also evaluated to have be associated with a profile change in the volatile compounds and non-volatile CGA compounds.

A standardized extract of Rhynchosia volubilis Lour. exerts a protective effect on benzalkonium chloride-induced mouse dry eye model.

ETHNOPHARMACOLOGICAL RELEVANCE: In contrast to other leguminous plants generally used as food, Rhynchosia volubilis Loureiro, a small soybean with a black seed coat, has been used as a traditional oriental remedy for various human diseases in Eastern Asia. In this study, we demonstrated the protective effect of R. volubilis against dry eye disease. AIM OF THE STUDY: We aimed to investigate whether a standardized ethanol extract of R. volubilis (EERV) can protect the cornea in a benzalkonium chloride (BAC)-induced mouse dry eye model. MATERIALS AND METHODS: Experimental dry eye was induced by the instillation of 0.2% BAC on mouse cornea. A standardized ethanol extract of R. volubilis (EERV) was orally administered following BAC treatment. The positive control group was treated with commercial eye drops. Fluorescein staining, tear break-up time (BUT), and hematoxylin and eosin staining were evaluated on the ocular surface. Squamous metaplasia and apoptosis in the corneal epithelial layer were detected by immunostaining. Furthermore, the protein expression of cytochrome c, Bcl-2, and Bax was determined. RESULTS: EERV treatment significantly improved fluorescein scoring, BUT, and smoothness in the cornea compared to the vehicle group. In addition, EERV inhibited squamous metaplasia and apoptosis in the cornea. The expression of cytochrome c and Bax was upregulated, while that of Bcl-2 was downregulated in the vehicle group compared with that in the control group. However, EERV treatment inhibited the expression of cytochrome c and Bax, while that of Bcl-2 was improved. CONCLUSION: Standardized EERV could be a beneficial candidate for the treatment of dry eye disease.

Persimmon Leaves (Diospyros kaki) Extract Protects Optic Nerve Crush-Induced Retinal Degeneration.

Retinal ganglion cell (RGC) death is part of many retinal diseases. Here, we report that the ethanol extract of Diospyros kaki (EEDK) exhibits protective properties against retinal degeneration, both in vitro and in vivo. Upon exposure to cytotoxic compounds, RGC-5 cells showed approximately 40% cell viability versus the control, while pre-treatment with EEDK markedly increased cell viability in a concentration-dependent manner. Further studies revealed that cell survival induced by EEDK was associated with decreased levels of apoptotic proteins, such as poly (ADP-ribose) polymerase, p53, and cleaved caspase-3. In addition to apoptotic pathways, we demonstrated that expression levels of antioxidant-associated proteins, such as superoxide dismutase-1, glutathione S-transferase, and glutathione peroxidase-1, were positively modulated by EEDK. In a partial optic nerve crush mouse model, EEDK had similar ameliorating effects on retinal degeneration resulting from mechanical damages. Therefore, our results suggest that EEDK may have therapeutic potential against retinal degenerative disorders, such as glaucoma.

Positive selection of type II collagen-reactive CD80high marginal zone B cells in DBA/1 mice.

To investigate whether dysregulated selection of autoreactive marginal zone (MZ) B cells is involved in autoimmune diseases, we examined MZ B cell profile in multiple strains of mice, and found that type II collagen (CII)-reactive autoreactive CD80high MZ B cells spontaneously developed in the DBA/1, but not in C57BL/6 mice. CD80high MZ B cells that were characteristically found in DBA/1 mice expressed higher levels of TACI, SLAM3, and SLAM6 than the usual CD80low MZ B cells. Notably, the CD80high MZ B cells were more sensitive to ibrutinib, a Bruton's tyrosine kinase inhibitor, than CD80low MZ or follicular B cells and their transient depletion via intravenous injection of ibrutinib significantly delayed the induction of collagen-induced arthritis (CIA). In summary, we suggest that the positive selection of CII-reactive CD80high MZ B cells is a critical homeostatic process predisposing the DBA/1 mice to the CIA induction.

Combined treatment with zingerone and its novel derivative synergistically inhibits TGF-ß1 induced epithelial-mesenchymal transition, migration and invasion of human hepatocellular carcinoma cells.

The epithelial-mesenchymal transition (EMT) is an important cellular process during which polarized epithelial cells become motile mesenchymal cells, which promote cancer metastasis. Ginger, the rhizome of Zingiber officinale, is extensively used in cooking worldwide and also as a traditional medicinal herb with antioxidant, anti-inflammatory and anticancer properties. Several pungent compounds have been identified in ginger, including zingerone, which has anticancer potential. However, the role of zingerone in EMT is unclear. We investigated the synergistic effect of zingerone and its derivative on EMT. Transforming growth factor-beta 1 (TGF-ß1) induces the EMT to promote hepatocellular carcinoma metastasis, including migration and invasion. To understand the repressive role of the combination of zingerone and its derivative (ZD 2) in hepatocellular carcinoma metastasis, we investigated the potential use of each compound of ginger, such as zingerone, ZD 2 and 6-shogaol, or the mixture of zingerone and ZD 2 (ZD 2-1) as inhibitors of TGF-ß1 induced EMT development in SNU182 hepatocellular carcinoma cells in vitro. We show that ZD 2-1, but not zingerone, ZD 2 and 6-shogaol significantly increased expression of the epithelial marker E-cadherin and repressed Snail upregulation and expression of the mesenchymal marker N-cadherin during initiation of the TGF-ß1 induced EMT. In addition, ZD 2-1 inhibited the TGF-ß1 induced increase in cell migration and invasion of SNU182 hepatocellular carcinoma cells. Furthermore, ZD 2-1 significantly inhibited TGF-ß1 regulated matrix metalloproteinase-2/9 and activation of Smad2/3. We also found that ZD 2-1 inhibited nuclear translocation of NF-κB, activation of p42/44 MAPK/AP1 signaling pathway in the TGF-ß1 induced EMT. Our findings provide new evidence that combined treatment with ZD 2, novel zingerone derivative, and zingerone synergistically suppresses hepatocellular carcinoma metastasis in vitro by inhibiting the TGF-ß1 induced EMT.

The Natural Substance MS-10 Improves and Prevents Menopausal Symptoms, Including Colpoxerosis, in Clinical Research.

Many natural substances were screened to develop nutraceuticals that reduce menopausal symptoms. A complex of Cirsium japonicum var. maackii and Thymus vulgaris extracts, named MS-10, had significant positive effects. Under a low concentration of estrogen, which represents postmenopausal physiological conditions, MS-10 had beneficial effects on estrogen receptor-expressing MCF-7 cells by reversibly enhancing estrogen activity. In addition, in the ovariectomized rat model, changes in bone-specific alkaline phosphatase activity and osteocalcin, as well as low-density lipoprotein cholesterol and triglyceride levels were significantly decreased by MS-10. These results show that MS-10 protected bone health and reduced metabolic disturbances. Furthermore, in a clinical study, all menopausal symptoms, including hot flushes, parenthesis, insomnia, nervousness, melancholia, vertigo, fatigue, rheumatic pain, palpitations, formication, and headache, as well as colpoxerosis, were significantly improved by taking MS-10 for 90 days. Therefore, the evidence supports that MS-10 is an effective natural substance that can safely improve menopausal symptoms, including colpoxerosis.

Platelet-rich plasma therapy for knee joint problems: review of the literature, current practice and legal perspectives in Korea.

Platelet-rich plasma (PRP) is a concentrate extract of platelets from autologous blood, and represents a possible treatment option for the stimulation and acceleration of soft-tissue healing and regeneration in orthopedics. Currently, the availability of devices for outpatient preparation and delivery contributes to the increase in the clinical use of PRP therapy in practical setting of orthopedic fields. However, there is still paucity of scientific evidence in the literature to prove efficacy of PRP therapy for the treatment of ligament or tendon problems around the knee joint. Moreover, strong evidence from well-designed clinical trials to support the PRP therapy for osteoarthritis of the knee joint is yet scanty in the literature. Scientific studies need to be performed to assess clinical indications, efficacy, and safety of PRP, and this will require high powered randomized controlled trials. Nonetheless, some hospitals exaggeratedly advertise PRP procedures as the ultimate treatment and a novel technology with abundant scientific evidence for the treatment of knee problems. As a matter of fact, PRP protocols are currently approved only for use in clinical trials and research, and are not allowed for treatment purpose by any institutions in Korea. At present, clinical use of PRP therapy for ligament or tendon problems or osteoarthritis of knee joint is defined as illegal medical practice, regardless of whether it is performed as a sole procedure or as a part of prolotherapy, because the safety and validity are not yet approved by the Ministry of Health and Welfare and Health Insurance Review and Assessment Service. Practicing physicians should remember that injection of PRP to patients by imposing medical charge is still illegal as per the current medical law in Korea.

Dietary ungerminated and germinated soybean supplementation improves bone mineralization and strength in growing male rats.

It has been thought that soybean products rich in phytoestrogenic isoflavones are effective in promoting bone metabolism in ovariectomized rats. However, it is not clear if such an effect can be changed by germination of soybean and can be observed in growing males. The present study was undertaken to determine the effects of different concentrations of dietary ungerminated and germinated soybean (UGS and GS, respectively) on bone metabolism in young male rats. Forty-nine 6-week-old male Sprague-Dawley rats were assigned to seven dietary treatment groups: AIN 93G (control); control with UGS powder at 3% (UGS-L), 15% (UGS-M), or 30% (UGS-H); and control with GS powder at 3% (GS-L), 15% (GS-M), or 30% (GS-H). The biomarkers of bone metabolism (plasma and urinary Ca and P) and the physical properties and mineral content of bones were measured. Plasma osteocalcin and urinary deoxypyridinoline levels were not affected by soybean diets. The plasma P level was significantly elevated by dietary soybeans (P < .001). However, there was a negative correlation (r = -0.555) between plasma P level and dietary UGS level (P < .01). Between the UGS and GS groups, the P level of the GS-M group was significantly higher than that of the UGS-M group (P < .001). The tibial weight was decreased with low to medium doses of soybeans, but not with higher levels. Femoral bone strength was improved in the UGS-H, GS-M, and GS-H groups. The P contents of femoral and tibial bones were increased in all UGS groups as well as in GS-M and GS-H groups. In conclusion, soybean supplementation in young growing male rats improved bone mineralization and bone strength.

Regulation of pro-inflammatory responses by lipoxygenases via intracellular reactive oxygen species in vitro and in vivo.

Reactive oxygen species (ROS) performs a pivotal function as a signaling mediator in receptor-mediated signaling. However, the sources of ROS in this signaling have yet to be determined, but may include lipoxygenases (LOXs) and NADPH oxidase. The stimulation of lymphoid cells with TNF-alpha, IL-1beta, and LPS resulted in significant ROS production and NF-kappaB activation. Intriguingly, these responses were markedly abolished via treatment with the LOXs inhibitor nordihydroguaiaretic acid (NDGA). We further examined in vivo anti-inflammatory effects of NDGA in allergic airway inflammation. Both intraperitoneal and intravenous NDGA administration attenuated ovalbumin (OVA)-induced influx into the lungs of total leukocytes, as well as IL-4, IL-5, IL-13, and TNF-alpha levels. NDGA also significantly reduced serum levels of OVA-specific IgE and suppressed OVA-induced airway hyperresponsiveness to inhaled methacholine. The results of our histological studies and flow cytometric analyses showed that NDGA inhibits OVA-induced lung inflammation and the infiltration of CD11b+ macrophages into the lung. Collectively, our findings indicate that LOXs performs an essential function in pro-inflammatory signaling via the regulation of ROS regulation, and also that the inhibition of LOXs activity may have therapeutic potential with regard to the treatment of allergic airway inflammation.

Flavonoids from the leaves of Litsea japonica and their anti-complement activity.

Four flavonoids, epicatechin (1), afzelin (2), quercitrin (3), and tiliroside (4), were isolated from the leaves of Litsea japonica (Thunb.) Jussieu (Lauraceae). The structures of compounds were identified by comparing their chemical and spectral data with those previously reported. The flavonoids (1-4) were tested for their anti-complement activity against classical pathway of complement system. Compounds 2-4 showed inhibitory activity against complement system with IC50 values of 258, 440, and 101 microm, respectively, whereas 1 was inactive. For the evaluation of the structure-activity relationship of 5,7-dihydroxyflavones, myricitrin (5) from Juglans mandshurica also tested for it's anti-complement activity and is inactive in this assay system. Furthermore, compounds 2, 3, and 5 were hydrolyzed with naringinase to give kaempferol (2a), quercetin (3a), and myricetin (5a), and these were also tested for their activity. Of the three aglycones, 2a exhibited anti-complement activity with an IC50 value of 730 microM, while 3a and 5a were inactive. The inhibitory potencies of 2, 2a, 3, 3a, 5, and 5a against complement activity increased in inverse proportion to number of free hydroxyls on B-ring of 5,7-dihydroxyflavone. Of the compounds tested, 4 showed the most potent inhibitory activity against the complement system.

Isolation and anticomplement activity of compounds from Dendropanax morbifera.

Dendropanax morbifera Leveille (Araliaceae) is used in Korea for a variety of disease, such as migraine headache and dysmenorrhea. A new polyacetylene (1) and six known compounds (2-7) were isolated from the leaves of this plant by conventional chromatographic techniques. The structure of the new polyacetylene (1) was determined as (9Z,16S)-16-hydroxy-9,17-octadecadiene-12,14-diynoic acid by spectroscopic means including 2D NMR, which comprised the determination of a chiral by modified Mosher's ester method. Compounds 1-7 were investigated in vitro for their anticomplement activity against the classical pathway of the complement system. Of these, compound 1 showed significant anticomplement activity with 50% inhibitory concentration (IC50) value of 56.98 microM, whereas compounds 2-7 were inactive.

Lactones from the leaves of Litsea japonica and their anti-complement activity.

Two new lactones, litsealactone A (1) and litsealactone B (2), were isolated from the leaves of Litsea japonica, together with three known lactones, hamabiwalactone A (3), hamabiwalactone B (4), and akolactone B (5). Hamabiwalactone B (4) and akolactone B (5) significantly inhibited complement activity in an in vitro anti-complement assay, with IC(50) values of 149 and 58 muM, respectively.

Anti-complement activity of constituents from the stem-bark of Juglans mandshurica.

Four known flavonoids and two galloyl glucoses isolated from the stem-bark of Juglans mandshurica (Juglandaceae), namely taxifolin (1), afzelin (2), quercitrin (3), myricitrin (4), 1,2,6-trigalloylglucose (5), and 1,2,3,6-tetragalloylglucose (6), were evaluated for their anti-complement activity against complement system. Afzelin (2) and quercitrin (3) showed inhibitory activity against complement system with 50% inhibitory concentrations (IC(50)) values of 258 and 440 microM. 1,2,6-Trigalloylglucose (5) and 1,2,3,6-tetragalloylglucose (6) exhibited anti-complement activity with IC(50) values of 136 and 34 microM. In terms of the evaluation of the structure-activity relationship of 3,5,7-trihydroxyflavone, compounds 2, 3, and 4 were hydrolyzed with naringinase to give kaempferol (2a), quercetin (3a), and myricetin (4a) as their aglycones, and these were also tested for their anti-complement activity. Of the three aglycones, kaempferol (2a) exhibited weak anti-complement activity with an IC(50) value of 730 microM, while quercetin (3a) and myricetin (4a) were inactive in this assay system. Among the compounds tested, 1,2,3,6-tetragalloylglucose (6) showed the most potent anticomplement activity (IC(50), 34 microM).

Biophoton emission from fingernails and fingerprints of living human subjects.

Biophotons emitted from the center of fingernails and fingerprints from living humans are measured for twenty healthy subjects. We devised a dark box with a photo multiplier tube (H6180-01, Hamamatsu, Japan) whose spectral range is 300 nm to approximately 650 nm and a mount with a light-receiving hole of diameter 8 mm such that biophotons from the small circular area of nail or print of each finger are detected. Significantly more biophotons are emitted from fingernail than fingerprint for each finger of every subject. For thumb the average biophoton emission rate is 23.0 +/- 4.5 counts per second, and 17.2 +/- 2.0 counts per second from the nail, and print, respectively. There is a slight tendency that the little finger emits less than the other fingers. But some fingers emit far stronger than others, and it depends upon each individual subject which finger emits strongest.