Shikonin alleviates choroidal neovascularization by inhibiting proangiogenic factor production from infiltrating macrophages.

Choroidal neovascularization (CNV), a feature of neovasular age-related macular degeneration (AMD), acts as a leading cause of vision loss in the elderly. Shikonin (SHI), a natural bioactive compound extracted from Chinese herb radix arnebiae, exerts anti-inflammatory and anti-angiogenic roles and also acts as a potential pyruvate kinase M2 (PKM2) inhibitor in macrophages. The major immune cells macrophages infiltrate the CNV lesions, where the production of pro-angiognic cytokines from macrophage facilitates the development of CNV. PKM2 contributes to the neovascular diseases. In this study, we found that SHI oral gavage alleviated the leakage, area and volume of mouse laser-induced CNV lesion and inhibited macrophage infiltration without ocular cytotoxicity. Moreover, SHI inhibited the secretion of pro-angiogenic cytokine, including basic fibroblast growth factor (FGF2), insulin-like growth factor-1 (IGF1), chemokine (C-C motif) ligand 2 (CCL2), placental growth factor and vascular endothelial growth factor (VEGF), from primary human macrophages by down-regulating PKM2/STAT3/CD163 pathway, indicating a novel potential therapy strategy for CNV.

Long-Term Tea Consumption Is Associated with Reduced Risk of Diabetic Retinopathy: A Cross-Sectional Survey among Elderly Chinese from Rural Communities.

AIM: To investigate the association between variables related to tea consumption (duration, frequency, and type) and the risk of diabetic retinopathy. METHODS: A rural community-based, cross-sectional survey was conducted in Weitang Town, Suzhou, China. People aged 60 years or above were invited to complete the survey. All eligible patients underwent detailed eye examination. Diabetic retinopathy (DR) was diagnosed and graded based on the retinal fundus imaging. Diabetes was defined as fasting glucose concentrations of ≥7.0 mmol/L or self-reported diagnosis of diabetes. Information about tea consumption such as duration, type, and frequency, together with demographics and lifestyle characteristics, were collected using a face-to-face questionnaire interview. The association between tea consumption and the risk of DR was determined by univariate and multivariate logistic regression analyses. RESULTS: Among the 5,281 participants, 614 had diabetes mellitus (prevalence of 11.63%). The prevalence rate of DR was 10.38% in the diabetic population and 1.04% in the general population. Compared with non-tea consumers, the crude OR values for DR in subjects with long-term and short-term tea consumption were 0.34 (95%CI = 0.14-0.82, p = 0.016) and 1.64 (95%CI = 0.74-3.64, p = 0.221), respectively. When adjusted for age, gender, and other confounders, consumption of tea for ≥20 years was associated with reduced odds of DR (OR = 0.29, 95%CI = 0.09-0.97, p = 0.044). Thus, long-term tea consumption was significantly associated with a lower risk of DR. There was no statistical significance between frequency or type of tea consumption with DR (p > 0.05). CONCLUSION: Elderly diabetic Chinese residents who consumed tea for more than twenty years had a lower risk of DR compared to non-tea consumers. The long-term tea consumption may be an independent protective factor for DR. However, further studies are warranted to examine the association.

A yellow-emitting phosphor of Mn(2+)-doped Na2CaP2O7.

A yellow-emitting Na2CaP2O7:Mn(2+)phosphors have been synthesized by solid state reaction. The crystal structure, photoluminescence properties as well as concentration quenching mechanism have been investigated. The (4)T1-(6)A1 emission of Mn(2+)in Na2CaP2O7 phosphor ranges from 500 to 650 nm and exhibits a red shift while increasing the Mn(2+)concentration. The crystal field strength is calculated based on the combination of excitation spectrum and Tanabe-Sugano diagram. The chromaticity coordinates of Na2CaP2O7:Eu(2+), Mn(2+)phosphors were discussed in order to develop the potential application in white light-emitting diodes (LEDs).

Zeaxanthin Induces Apoptosis in Human Uveal Melanoma Cells through Bcl-2 Family Proteins and Intrinsic Apoptosis Pathway.

The cytotoxic effects of zeaxanthin on two human uveal melanoma cell lines (SP6.5 and C918) and related signaling pathways were studied and compared to effects on normal ocular cells (uveal melanocytes, retinal pigment epithelial cells, and scleral fibroblasts). MTT assay revealed that zeaxanthin reduced the cell viability of melanoma cells in a dose-dependent manner (10, 30, and 100 µ M), with IC50 at 40.8 and 28.7 µ M in SP6.5 and C918 cell lines, respectively. Zeaxanthin did not affect the viability of normal ocular cells even at the highest levels tested (300 µ M), suggesting that zeaxanthin has a selectively cytotoxic effect on melanoma cells. Zeaxanthin induced apoptosis in melanoma cells as indicated by annexin V and ethidium III flow cytometry. Western blot analysis demonstrated that zeaxanthin decreased the expression of antiapoptotic proteins (Bcl-2 and Bcl-xL) and increased the expression of proapoptotic proteins (Bak and Bax) in zeaxanthin-treated melanoma cells. Zeaxanthin increased mitochondrial permeability as determined by JC-1 fluorescein study. Zeaxanthin also increased the level of cytosol cytochrome c and caspase-9 and -3 activities, but not caspase-8, as measured by ELISA assay or colorimetric assay. All of these findings indicate that the intrinsic (mitochondrial) pathway is involved in zeaxanthin-induced apoptosis in uveal melanoma cells.

Cordycepin inhibits IL-1beta-induced MMP-1 and MMP-3 expression in rheumatoid arthritis synovial fibroblasts.

OBJECTIVE: MMP is a key enzyme in the degradation of extracellular matrices, and its expression plays important roles in inflammatory diseases. Cordycepin (3'-deoxyadenosine), a bioactive compound of Cordyceps militaris, has been shown to exhibit many pharmacological activities, such as anti-cancer, anti-inflammatory and anti-infection activities. In this study, we aimed at the inhibitory effect of cordycepin on IL-1beta-induced MMP-1 and MMP-3 expression as well as the molecular basis using RA synovial fibroblasts (RASFs). METHODS: RASFs were isolated from synovial tissue obtained from 12 patients with RA and cultured in monolayer. Expression of MMP-1 and MMP-3 was evaluated using western blotting and real-time PCR. Chemokines were analysed by ELISA. The phosphorylation of mitogen-activated protein kinase was measured by western blotting. Electrophoretic mobility shift assay was performed to evaluate binding activities of DNA to nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). RESULTS: Cordycepin inhibited IL-1beta-induced MMP-1 and MMP-3 expressions in RASFs in a dose-dependent manner. Among various chemokines [such as monocyte chemoattractant protein-1 (MCP-1), GRO-alpha, regulated upon activation, normal T-cell expressed and presumably secreted (RANTES) and epithelial neutrophil activating peptide 78 (ENA-78)], cordycepin specifically blocked IL-1beta-induced ENA-78 production in RASF. Moreover, cordycepin significantly inhibited IL-1beta-induced p38/JNK and AP-1 activation, but not extracellular signal-regulated kinase (ERK) and NF-kappaB activation. CONCLUSIONS: Cordycepin is a potent inhibitor of IL-1beta-induced chemokine production and MMP expression and strongly blocks the p38/JNK/AP-1 signalling pathway in RASFs.

Quantitative brain MRI in alcohol dependence: preliminary evidence for effects of concurrent chronic cigarette smoking on regional brain volumes.

BACKGROUND: Recent in vivo research using magnetic resonance spectroscopy demonstrated that chronic cigarette smoking exacerbates regional chronic alcohol-induced brain injury. Other studies associated cigarette smoking with gray matter volume reductions in healthy adults, with greater brain atrophy in aging, and with poorer neurocognition. Although cigarette smoking is common among alcohol-dependent individuals, previous research did not account for the potential effects of chronic smoking on regional brain volumes in alcoholism. METHODS: High-resolution T1-weighted magnetic resonance images from one-week-abstinent, alcohol-dependent individuals and light drinkers were automatically segmented into gray matter, white matter, and cerebral spinal fluid of lobes and subcortical structures. A brief neuropsychological test battery was used to assess cognition in alcohol-dependent individuals. The alcoholic and nondrinking groups were retrospectively divided into chronic smokers and nonsmokers, and the volumetric data were analyzed as a function of alcohol and smoking status. RESULTS: Chronic alcohol dependence was associated with smaller volumes of frontal and parietal white matter, parietal and temporal gray matter, and thalami, accompanied by widespread sulcal but not ventricular enlargements. Chronic cigarette smoking was associated with less parietal and temporal gray matter and with more temporal white matter. Among alcoholics, better visuospatial learning and memory and greater visuomotor scanning speed were correlated with larger lobar white matter volumes in the nonsmoking alcohol-dependent group only. CONCLUSIONS: These data provide preliminary evidence that comorbid chronic cigarette smoking accounts for some of the variance associated with cortical gray matter loss and appears to alter relationships between brain structure and cognitive functions in alcohol-dependent individuals.

Bakuchiol: a hepatoprotective compound of Psoralea corylifolia on tacrine-induced cytotoxicity in Hep G2 cells.

Bioassay-guided fractionation of the H(2)O extract of the seeds of Psoralea corylifolia furnished one hepatoprotective compound, bakuchiol (1), together with two moderately active compounds, bakuchicin (2) and psoralen (3), on tacrine-induced cytotoxicity in human liver-derived Hep G2 cells. The EC(50) values of compounds 1 - 3 are 1.0, 47.0, 50.0 microg/ml, respectively. Silymarin as a positive control showed the EC(50) value with 5.0 microg/ml.

Diarylheptanoids with free radical scavenging and hepatoprotective activity in vitro from Curcuma longa.

Assay-guided fractionation of the EtOAc soluble fraction of the rhizomes of Curcuma longa furnished three DPPH free radical scavenging diarylheptanoids, curcumin (1), demethoxycurcumin (2), and bisdemethoxycurcumin (3). Compounds 1-3 showed the DPPH radical scavenging effects with IC(50) values of 2.8, 39.2, 308.7 microM, respectively. L-Ascorbic acid and resveratrol as positive controls exhibited IC(50) values of 22.5 and 25.0 microM, respectively. Compounds 1-3 showed significant hepatoprotective effects on tacrine-induced cytotoxicity in human liver-derived Hep G2 cells. The EC(50) values of 1-3 are 86.9, 70.7, and 50.2 microM, respectively. Silybin (EC(50) = 69.0 microM) and silychristin (EC(50) = 82.7 microM) were used as positive controls.

Inhibitory effects of butanol fraction of the aqueous extract of Forsythia koreana on the nitric oxide production by murine macrophage-like RAW 264.7 cells.

The aim of this study was to investigate the effect of butanol fraction of the aqueous extract of Forsythia koreana fruits on the nitric oxide (NO) production and inducible nitric oxide synthesis (iNOS) gene expression in murine macrophage-like RAW 264.7 cells. Butanol fraction alone affected neither NO production nor iNOS gene expression in macrophage-like RAW 264.7 cells. However, the butanol fraction inhibited NO production and iNOS gene expression in RAW 264. 7 cells stimulated with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). These findings suggest that inhibition of NO production by this butanol fraction in RAW 264.7 cells stimulated with IFN-gamma plus LPS was due to the suppression of iNOS gene expression.

Cross-talk between N-methyl-D-aspartate and adrenergic neurotransmission in the regulation of hypothalamic GnRH gene expression.

Although it has been known that activation of N-methyl-D-aspartate (NMDA) receptor effectively stimulates GnRH biosynthesis and release from the rat hypothalamus, no evidence that NMDA receptors exist in GnRH neurons is yet available. It is then presumed that the action of NMDA on GnRH neurons may be indirectly mediated through interneurons, such as catecholamines. The present study is designed to investigate whether the effect of NMDA on GnRH gene expression is mediated by adrenergic neuronal system. Adrenergic receptor antagonists were administered 30 min prior to NMDA administration to immature male rats and then animals sacrificed 60 min after NMDA administration. GnRH mRNA levels were determined by Northern blot analysis using a GnRH RNA probe. Inhibition of either alpha 1 adrenergic receptor with prazosin or beta adrenergic receptor with propranolol did not cause any change in the basal GnRH mRNA levels but reduced NMDA-induced GnRH mRNA levels. However, inhibition of alpha 2 adrenergic receptor with yohimbine increased GnRH mRNA levels but did not affect NMDA-induced GnRH mRNA levels. These findings suggest that the effect of NMDA on GnRH gene expression is mediated through adrenergic neurotransmission.