Ulmus davidiana 60% edible ethanolic extract for prevention of pericyte apoptosis in diabetic retinopathy.

Diabetic retinopathy (DR) is a disease that causes visual deficiency owing to vascular leakage or abnormal angiogenesis. Pericyte apoptosis is considered one of the main causes of vascular leakage in diabetic retina, but there are few known therapeutic agents that prevent it. Ulmus davidiana is a safe natural product that has been used in traditional medicine and is attracting attention as a potential treatment for various diseases, but its effect on pericyte loss or vascular leakage in DR is not known at all. In the present study, we investigated on the effects of 60% edible ethanolic extract of U. davidiana (U60E) and catechin 7-O-ß-D-apiofuranoside (C7A), a compound of U. davidiana, on pericyte survival and endothelial permeability. U60E and C7A prevented pericyte apoptosis by inhibiting the activation of p38 and JNK induced by increased glucose and tumor necrosis factor alpha (TNF-α) levels in diabetic retina. Moreover, U60E and C7A reduced endothelial permeability by preventing pericyte apoptosis in co-cultures of pericytes and endothelial cells. These results suggest that U60E and C7A could be a potential therapeutic agent for reducing vascular leakage by preventing pericyte apoptosis in DR.

Anisotropic Angstrom-Wide Conductive Channels in Black Phosphorus by Top-down Cu Intercalation.

Intercalation in black phosphorus (BP) can induce and modulate a variety of the properties including superconductivity like other two-dimensional (2D) materials. In this perspective, spatially controlled intercalation has the possibility to incorporate different properties into a single crystal of BP. We demonstrate anisotropic angstrom-wide (∼4.3 Å) Cu intercalation in BP, where Cu atoms are intercalated along a zigzag direction of BP because of its inherent anisotropy. With atomic structure, its microstructural effects, arising from the angstrom-wide Cu intercalation, were investigated and extended to relation with macrostructure. As the intercalation mechanism, it was revealed by in situ transmission electron microscopy and theoretical calculation that Cu atoms are intercalated through top-down direction of BP. The Cu intercalation anisotropically induces transition of angstrom-wide electronic channels from semiconductor to semimetal in BP. Our findings throw light on the fundamental relationship between microstructure changes and properties in intercalated BP, and tailoring anisotropic 2D materials at angstrom scale.

Improved infrared spectroscopic discrimination between gall bladder (GB) polyps and GB cancer using component-descriptive spectral features of separated phases from bile.

This study demonstrates a unique strategy for enhancing infrared (IR) spectroscopic discrimination between gall bladder (GB) polyps and cancer. This strategy includes the separation of raw bile juice into three sections of organic, aqueous, and amphiphilic phases and a cooperative combination of all IR spectral features of each separated phase for the discrimination. Raw bile juice is viscous and complex in composition because it contains fatty acids, cholesterol, proteins, phospholipids, bilirubin, and other components; therefore, the acquisition of IR spectra providing more component-discernible information is fundamental for improving discrimination. For this purpose, raw bile juice was separated into an aqueous phase, mostly containing bile salts, an organic phase with isolated lipids, and an amphiphilic phase, mainly containing proteins. The subsequent IR spectra of each separated phase were mutually characteristic and complementary to each other. When all the IR spectral features were combined, the discrimination was improved compared to that using the spectra of raw bile juice with no separation. The cooperative integration of more component-specific spectra obtained from each separated phase enhanced the discrimination. In addition, the IR spectra of the major constituents in bile juice, such as bile acids, conjugated bile salts, lecithin, and cholesterol, were recorded to explain the IR features of each separated phase.

Effects of active dried Saccharomyces cerevisiae on ruminal fermentation and bacterial community during the short-term ruminal acidosis challenge model in Holstein calves.

We investigated the effects of active dried Saccharomyces cerevisiae (ADSC) on ruminal pH, fermentation, and the fluid bacterial community during the short-term ruminal acidosis challenge. Five rumen-fistulated male Holstein calves (147.0 ± 5.8 kg of body weight; 3.6 ± 0.2 mo of age) were used in a crossover design, and 0 g (control group, n = 5) or 2 g (SC group, n = 5) of ADSC (1 × 1010 cfu/g) was administered twice daily for 21 consecutive days. Calves were fed a high-forage diet during the first 15 d (d -14 to d 0; prechallenge), a high-grain diet for 2 d (d 1 and 2; ruminal acidosis challenge), and a high-forage diet for 4 d (d 3 to 6; postchallenge). Ruminal pH was measured continuously. Rumen fluid samples were collected once daily (0800 h) on d 0, 3, 4, and 6 and twice daily (0800 and 1100 h) on d 1 and 2. Bacterial DNA was extracted from fluid samples collected on d 0 and 3. The 24-h and 1-h mean ruminal pH was significantly depressed during the ruminal acidosis challenge in each group, although the changes were more severe in the SC group, consistent with a significant increase in lactic acid on d 2 (1100 h) compared with d 0 and a significantly higher proportion of butyric acid on d 2 (1100 h) compared with the control group. Feeding a high-grain diet caused a decrease in bacterial diversity due to high acidity in both groups. The relative abundances of the genus Bifidobacterium and operational taxonomic unit (OTU) 3 (Bifidobacterium species) increased significantly in both groups but were higher in the SC group. Correlation analyses indicated that OTU3 (Bifidobacterium species) were positively correlated with lactic acid concentration and that OTU1 (Prevotella species) and OTU5 (Succinivibrio species) were correlated with the proportion of butyric acid. These results suggest that ADSC supplementation induced the intense decreases in ruminal pH by increased butyric and lactic acid production through a high-grain diet fermentation by rumen fluid bacterial species during the short-term ruminal acidosis challenge in Holstein calves after weaning.

(2S)-naringenin from Typha angustata inhibits vascular smooth muscle cell proliferation via a G0/G1 arrest.

ETHNOPHARMACOLOGICAL RELEVANCE: Typha angustata is used in traditional Chinese medicine for a variety of clinical disorders. Its pharmacological actions include beneficial effects on hyperlipidemia and myocardial infarction, as well as labor-inducing and antibacterial effects. AIM OF THE STUDY: We investigated the mechanism underlying the ability of (2S)-naringenin, an active compound from Typha angustata, to inhibit the proliferation of vascular smooth muscle cells (VSMCs). MATERIALS AND METHODS: After measuring the antiproliferative effect of (2S)-naringenin on VSMC proliferation using cell proliferation and viability assays, the possible involvement of a signaling pathway associated with platelet-derived growth factor receptor ß (PDGF-Rß), extracellular signal regulated kinase 1/2 (ERK1/2), phosphatidylinositol 3-kinase (PI3K)-linked protein kinase B (Akt/PKB), or phospholipase C-γ1 (PLCγ1) was investigated by immunoblotting. Moreover, the effect of (2S)-naringenin on DNA synthesis and the cell cycle was examined using a [(3)H]-thymidine incorporation assay and flow cytometry. RESULTS: (2S)-Naringenin significantly inhibited PDGF-BB-induced VSMC proliferation in a concentration-dependent manner, but did not affect signaling pathways associated with PDGF-Rß, Akt/PKB, ERK1/2, or PLCγ1. However, (2S)-naringenin suppressed DNA synthesis via a G(0)/G(1) cell cycle arrest. Accordingly, the expression of cyclins D1 and E and cyclin-dependent kinases 2 and 4 was inhibited in a concentration-dependent manner; moreover, the phosphorylation of retinoblastoma protein was suppressed. CONCLUSIONS: Our results show that (2S)-naringenin inhibited the PDGF-BB-induced proliferation of VSMCs via a G(0)/G(1) arrest; thus, (2S)-naringenin may be valuable as a therapeutic agent for managing atherosclerosis and/or vascular restenosis.

A new iridoid and effect on the rat aortic vascular smooth muscle cell proliferation of isolated compounds from Buddleja officinalis.

A new iridoid, named methylscutelloside (1) together with 19 known compounds belonging to the iridoids (2-4), monoterpenoids (5), flavonoids (6-8), triterpenoids (9-14), and phenylethanoids (15-20) were isolated from the flowers of Buddleja officinalis. Their chemical structures were elucidated on the basis of physicochemical properties, and by spectroscopic methods including 1D, 2D NMR, and MS. All isolated compounds were tested in vitro for their effects on the proliferation of rat aortic vascular smooth muscle cells (VSMCs). Among them, iridoids were the main active components and showed significant inhibitory effects on PDGF-BB-induced proliferation in rat aortic VSMCs.

7-O-methylaromadendrin stimulates glucose uptake and improves insulin resistance in vitro.

The stimulation of glucose uptake into peripheral tissues is an important mechanism for the removal of glucose in blood and for the management of diabetes mellitus (DM). Since recent results have demonstrated the beneficial effects of flavonoids in relation to DM, this study was designed to examine the effects of 7-O-methylaromadendrin (7-O-MA), a flavonoid isolated from Inula viscosa, on glucose uptake into liver and fat tissue, and investigate the molecular mechanisms involved. 7-O-MA at 10 microM significantly stimulated insulin-induced glucose uptake measured by 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG) in both human hepatocellular liver carcinoma (HepG2) cells and differentiated 3T3-L1 adipocytes. Adipocyte-specific fatty acid binding protein (aP2) gene expression was increased by 7-O-MA in adipocytes, and both gene and protein level of peroxisome proliferator-activated receptor gamma2 (PPARgamma2) was also increased. Moreover, 7-O-MA stimulated the reactivation of insulin-mediated phosphorylation of phosphatidylinositol 3-kinase (PI3K)-linked protein kinase B (Akt/PKB) and adenosine 5'-monophosphate-activated protein kinase (AMPK) in high glucose-induced, insulin-resistant HepG2 cells, and this effect was blocked by either LY294002, a PI3K inhibitor, or compound C, an AMPK inhibitor. Therefore, these results suggest that 7-O-MA might stimulate glucose uptake via PPARgamma2 activation and improve insulin resistance via PI3K and AMPK-dependent pathways, and be a potential candidate for the management of type 2 DM.

Differential regulation by Seogak Jihwang-Tang on cytokines production in peripheral blood mononuclear cells from the cerebral infarction patients presenting with altered consciousness.

Seogak Jihwang-Tang (SJT) has been widely used to treat patients suffering from cerebral infarction. However, very little scientific investigation has been carried out. We investigated the effect of SJT on the production of various cytokines using peripheral blood mononuclear cells from the cerebral infarction patients presenting with altered consciousness. The cytokines production was determined by enzyme-linked immunosorbent assay. The amount of IL-4, IL-10 and TGF-beta1 in culture supernatant significantly increased in the SJT, lipopolysaccharide (LPS) or PHA-treated cells compared to unstimulated cells (P < 0.05). We also showed that increased IL-4 and IL-10 levels by LPS or phytohaemagglutinin (PHA) were significantly inhibited by SJT in a dose-dependent manner. Maximal inhibition rate of IL-4 and IL-10 production by SJT was 45.6 +/- 3.3% and 61 +/- 4.7% for LPS-stimulated cells and 27.3 +/- 1.2% and 83.6 +/- 2% for PHA-stimulated cells, respectively (P < 0.05). On the other hand, SJT significantly increased the LPS or PHA-induced TGF-beta1 production (P < 0.05). These data suggest that SJT has a regulatory effect on the cytokines production, which might explain its beneficial effect in the treatment of cerebral infarction.