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Angiosarcoma is a malignant tumor of endovascular origin that can occur in any part of the body including the breast; however, angiosarcoma of the breast is quite rare. There are two sub-types of breast angiosarcoma. One of the subtypes, primary breast angiosarcoma, is very rare; only a few cases have been reported to date. Bilateral primary breast angiosarcoma is even rarer, and several cases have been reported in postmenopausal women. We report a case of a 34-year-old woman with primary bilateral angiosarcoma. She had no other significant medical history, such as breast surgery or radiotherapy, which can lead to secondary angiosarcoma of the breast. [ABSTRACT FROM AUTHOR]

The use of microorganisms and their secreted molecules to prevent plant diseases is considered an attractive alternative and way to supplement synthetic fungicides for the management of plant diseases. Strain BS062 was selected based on its ability to inhibit the mycelial growth of Botrytis cinerea, a major causal fungus of postharvest root rot of ginseng and strawberry gray mold disease. Strain BS062 was found to be closely related to Streptomyces hygroscopicus (99% similarity) on the basis of 16S ribosomal DNA sequence analysis. Postharvest root rot of ginseng and strawberry gray mold disease caused by B. cinerea were controlled up to 73.9% and 58%, respectively, upon treatment with culture broth of Streptomyces sp. BS062. These results suggest that strain BS062 may be a potential agent for controlling ginseng postharvest root rot and strawberry gray mold disease. [ABSTRACT FROM AUTHOR]

The article discusses the effect of lignans from the stems and leaves of plant brandisia hancei on vascular endothelial growth factor (VEGF)-induced vascular permeability and migration of dorsal longitudinal anastomotic vessel (DLAV) and human retinal endothelial cells (HRECs) in zebrafish model. Topic discussed include the use of brandisia hancei in traditional Chinese medicine; overexpression of VEGF; phytochemical study of the plant for the isolation of a new lignan glycoside.

The use of a microorganism, or its secretions, to prevent plant disease offers an attractive alternative or supplement to syrahetic fungicides for the management of plant disease without the negative effects of chemical control mechanisms. During a scleening for microorganisms with the potential to be used as microbial fungicides, Bacillus sp. BS061 was isolated from a plant leaf. The strain BS061 potently inhibited the mycelial growth of Botrytis cinerea, and significantly reduced disease incidence of pcwdery mildew in cucumber and strawberry. We also found that the culture filtrate of BS061 inhibited the mycelial growth of valous plant pathogens. [ABSTRACT FROM AUTHOR]

Aim/Hypothesis: Low-density lipoprotein (LDL) is subjected to glycoxidation in diabetes, and a novel signalling mechanism by which glycoxidised LDL functions in glomerular mesangial cells remains to be ascertained. Methods: We performed gene expression analysis in mouse glomerular mesangial cells treated with LDL modified by glycation and oxidation (GO-LDL, 100 mg/ml) for 48 h by using DNA microarray analysis and quantitative real-time PCR. We examined the GO-LDL-specific changes in gene and protein expression in mesangial cells and glomeruli of type 2 diabetic Zucker diabetic fatty (ZDF) rats. Results: By microarray profiling, we noted that GO-LDL treatment increased Axl receptor tyrosine kinase (Axl) mRNA expression (~2.5-fold, p<0.05) compared with normal LDL (N-LDL) treatment in mesangial cells. Treatment with GO-LDL also increased the protein levels of Axl and its ligand Gas6 as measured by Western blotting. These increases were inhibited by neutralising Axl receptor-specific antibody. Silencing Gas6 by siRNA inhibited GO-LDL-induced Axl expression in mesangial cells. Axl and Gas6 protein were also increased in cells cultured in high glucose (30 mM) or methylglyoxal (200 µM). Gas6 treatment increased the expression and secretion of TGF-β1 protein, a key regulator of extracellular matrix expression in the glomeruli of diabetic kidneys. Immunohistochemical analyses of glomeruli from 20-week-old ZDF rats exhibited increased Axl protein expression. Rottlerin, a selective PKC-d inhibitor, completely blocked Gas6-induced TGF-β1 expression. Conclusions/Interpretation: These data suggest that LDL modified by glycoxidation may mediate Axl/Gas6 pathway activation, and this mechanism may play a significant role in the pathogenesis of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

To identify effective herb to treat obesity, we screened 115 herbal extracts for inhibition of porcine pancreatic lipase (triacylg-ycerol acylhydrolase, EC 3.1.1.3) activity in vitro. Of the extracts tested, Cudrania tricuspidata leaves exhibited the most pronounced inhibitory effect on lipase activity with an IC50 value of 9.91 μg/mL. Antilipid absorption effects of C. tricuspidata leaves were examined in rats after oral administration of lipid emulsions containing 50 or 250 mg C. tricuspidata/kg body weight. Plasma triacylglycerol levels 2 h after the oral administration of emulsions containing C. tricuspidata were significantly reduced compared to the untreated group (P < 0.05). These results suggest that C. tricuspidata leaves may be useful for the treatment of obesity. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) have been implicated in the development of diabetic complications, including diabetic nephropathy. KIOM-79, an 80%ethanolic extract obtained from parched Puerariae Radix, gingeredMagnolia Cortex, Glycyrrhiza Radix and Euphorbia Radix, was investigated for its effects on the development of renal disease in Zucker diabetic fatty rats, an animal model of type 2 diabetes. In vitro inhibitory effect of KIOM-79 on AGEs cross-linking was examined by enzyme-linked immunosorbent assay (ELISA). KIOM-79 (50mg/kg/day) was given to Zucker diabetic fatty rats for 13 weeks. Body and kidney weight, blood glucose, glycated hemoglobin, urinary albumin and creatinine excretions were monitored. Kidney histopathology, collagen accumulation, fibrinogen and transforming growth factor-beta 1 (TGF-β1) expression were also examined. KIOM-79 reduced blood glucose, kidney weight, histologic renal damage and albuminuria in Zucker diabetic fatty rats. KIOM-79 prevented glomerulosclerosis, tubular degeneration, collagen deposition and podocyte apoptosis. In the renal cortex, TGF-β1, fibronectin mRNA and protein were significantly reduced by KIOM-79 treatment. KIOM-79 reduces AGEs accumulation in vivo, AGE-protein cross-linking and protein oxidation. KIOM-79 could be beneficial in preventing the progression of diabetic glomerularsclerosis in type 2 diabetic rats by attenuating AGEs deposition in the glomeruli. [ABSTRACT FROM AUTHOR]

Differential behavior of mesangial cells derived from 12/15-lipoxygenase knockout mice relative to control mice. The 12/15-lipoxygenase (12/15-LO) enzyme has been implicated in the pathogenesis of diabetic nephropathy since lipoxygenase products induce cellular hypertrophy and extracellular matrix deposition in mesangial cells. In this study, in order to determine the potential in vivo functional role of 12/15-LO in kidney disease, we compared mouse mesangial cells (MMCs) derived from 12/15-LO knockout mice with those from genetic control wild-type mice. MMCs were isolated from wild-type and 12/15-LO knockout mice. Cellular growth, activation of mitogen-activated protein kinases (MAPKs), transcription factors, superoxide levels, and fibronectin expression were compared in the two cell types. Levels of the 12/15-LO product and protein were lower in MMC from 12/15-LO knockout relative to wild-type. MMCs from 12/15-LO knockout mice grew slower than wild-type cells, and also showed lower rates of tritiated thymidine and leucine incorporation (21% and 15% of wild-type, respectively, P < 0.001). Levels of superoxide and the matrix protein fibronectin were also lower in 12/15-LO knockout mice cells. Serum and angiotensin II (Ang II)-stimulated activities of p38 or ERK1/2 MAPKs, and cyclic adenosine monophosphate (cAMP)-responsive element binding protein (CREB) transcription factor were lower in 12/15-LO knockout relative to wild-type cells. In addition, DNA binding and transcriptional activities of activated protein-1 (AP-1) and CREB were lower in 12/15-LO knockout cells. Furthermore, stable 12/15-LO overexpression in MMC led to reciprocal increase in p38 MAPK activation and fibronectin expression. The differential activation of oxidant stress, specific signaling pathways, transcription factors, and growth and matrix genes may lead to reduced growth and growth factor responses in 12/15-LO knockout versus wild-type MMCs. These results provide ex vivo functional evidence for the first time that 12/15-LO activation plays a key role in mesangial cell responses associated with renal diseases such as diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Cyclooxygenase-2 (COX-2) enzyme and its inflammatory products such as prostaglandin E[sub 2] (PGE[sub 2]) have been implicated in the pathogenesis of several inflammatory diseases. However their role in diabetic vascular disease is unclear. Advanced glycation end products (AGEs) act via their receptor, RAGE, to play a major role in diabetic complications. In this study, we investigated the effect of AGEs and S100b, a specific RAGE ligand, on the expression of COX-2 and the molecular mechanisms involved in cultured THP-1 monocytes and human peripheral blood monocytes. S100b treatment of THP-1 cells led to a significant 3-5-fold induction of COX-2 mRNA (p < 0.001). COX-2 protein and its product PGE[sub 2] were also increased, whereas COX-1 expression was unaffected. In vitro prepared AGE also induced COX-2 mRNA. S100b-induced COX-2 mRNA was blocked by an anti-RAGE antibody and by inhibitors of NF-κB (Bay117082), oxidant stress, protein kinase C, ERK, and p38 MAPKs. S100b (4-h treatment) significantly increased transcription from a human COX-2 promoter-luciferase construct (4-fold, p < 0.001). Promoter deletion analyses and inhibition of transcription by an NF-κB superrepressor mutant confirmed NF-κB involvement. This was further supported by inhibition of S100b-induced PGE[sub 2] by Bay11-7082. Additionally, S100b-induced adherence of THP-1 monocytes to vascular smooth muscle cells was blocked by the COX-2 inhibitor NS-398, Bay11-7082, inhibitors of ERK and p38 MAPK, and protein kinase C thereby indicating functional relevance. S100b also increased COX-2 mRNA expression in human peripheral blood monocytes from healthy donors. Moreover, COX-2 mRNA levels were clearly evident in monocytes obtained from diabetic patients but not from normal subjects. These results show for the first time that AGEs can augment inflammatory responses by up-regulating COX-2 via RAGE and multiple signaling pathways, thereby leading to monocyte activation and vascular cell dysfunction. [ABSTRACT FROM AUTHOR]

A Bacillus sp. BS061 significantly reduced disease incidence of gray mold and powdery mildew. To identify the active principle, the culture filtrate was partitioned between butanol and water. The antifungal activity against B. cinerea was evident in the butanol-soluble portion, and active substances were identified as cyclic lipopeptides, iturin A series, by nuclear magnetic resonance spectrometry (NMR) and mass analysis. Interestingly, antifungal activity against powdery mildew was observed in the water-soluble portion, suggesting that cyclic lipopeptides have no responsibility to suppress powdery mildew. This finding reveals that biocontrol agents of Bacillus origin suppress gray mold and powdery mildew through the secretion of different bioactive substances. [ABSTRACT FROM AUTHOR]

Cassiae semen is widely used for antipyrogenic, to improve eyesight, and to relax bowels in Korean traditional herbal medicines and prescriptions. Previous study showed that a BuOH-soluble fraction of Cassiae semen methanolic extract (CS) inhibits in-vitro formation of advanced glycation end products (AGEs) and also preventive effect on the development of diabetic nephropathy in STZ-induced diabetic rats. Using HPLC analysis of CS, three compounds are identified as rubrofusarin-6-O-β-D-gentiobioside, toralactone-9-O-β-D-gentiobioside, and cassiaside. Cyclooxygenase (COX)-2 is a potent proinflammatory molecule, plays an important role in inflammatory disease including diabetes and its expression was up regulated in experimental models of diabetic nephropathy. Aim of this study was to examine anti-inflammatory effect of CS by analyzing COX-2 expression in renal cortex of STZ-induced diabetic rats and AGEs treated glomerular mesangial cells (MC). Reverse transcription-polymerase chain reactions and enzyme-linked immunosorbent assay were used to evaluate COX-2 mRNA and its enzyme product, respectively. We observed increased COX-2 mRNA expression in cortical tissues from STZ-diabetic rats relative to corresponding control rats. Treating rat MC with AGEs also significantly increased COX-2 mRNA expression compare to corresponding untreated MC. However, administration of CS (200 mg/kg) to STZ-diabetic rats (6 weeks old) for 12 weeks significantly reduced COX-2 mRNA expression by 2 fold in cortical tissues (2.26±0.11 vs. 1.08±0.05, p<0.01) than the STZ-diabetic rats. In our in-vitro experiment, CS treatment of rat MC inhibits AGE induced COX-2 mRNA expression by 2 fold (1.89±0.09 vs. 0.98±0.06, p<0.05) that the untreated control. Thus it is worthwhile to be investigated further for its potential pharmacological effects in diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Pueraria lobata has been reported to have comprehensive pharmacological actions in treatment of diabetes and cardiovascular diseases. There is increasing evidence implicating transforming growth factor-beta2 (TGF-β2) in diabetic pathological states of the lens. We hypothesized that PO41-14-42-K1, a component of Pueraria lobata, may involved in the prevention of diabetic eye disease development. We have recently shown the inhibitory effect of PO41-14-42-K1 on advanced glycation end products (AGEs) formation in-vitro. We have examined, high glucose (HG) induced TGF-β2 expression in human lens epithelial (HLE-B3) cells. However, we have also shown, this HG induced TGF-β2 expression was inhibited by PO41-14-42-K1 both at mRNA and its protein level. The aim of the current study is to examine whether, PO41-14-42-K1 is capable of preventing lens opacity in ex-vivo similar to that seen in cataracts. PO41-14-42-K1 treatment (up to 5µg/ml) of HLE-B3 cells led to no significant effect on cell growth by MTT assay. Culturing HLE-B3 cells with 25 mM glucose (HG) induced (2-3 fold increase in) both TGF-β2 mRNA and it proteins levels (p<0.05). This HG induced increase in TGFβ2 expression in HLE-B3 cells was dose dependently inhibited by pre-treating PO41-14-42-K1 (1, 5 µg/mL, p<0.001 vs. HG). In organ culture experiment, PO41-14-42-K1 (1, 5 µg/mL) treatment inhibits, xylose-induced lenses opacity in a dose dependent manner (p<0.001 vs xylose-induced lenses, respectively) suggesting PO41-14-42-K1 may mediate, at least by part, the inhibition of formation of diabetic cataract. These findings show for the first time that PO41-14-42-K1 might be a potential drug for preventing diabetic cataract. [ABSTRACT FROM AUTHOR]

Examines the interaction of MAPK and 12-lipoxygenase pathways in growth and matrix protein expression in mesangial cells (MC). Activation of p[sup38MAPK] in MC matrix synthesis; Formation of arachidonic acid; Determination on the radioactivity in trichloroacetic acid-insoluble protein by scintillation counting.

A total of 62 bacterial isolates were obtained from Gomsohang mud flat, Mohang mud flat, and Jeju Island, Republic of Korea. Among them, the isolate CNU114001 showed significant antagonistic activity against pathogenic fungi by dual culture method. The isolate CNU114001 was identified as Bacillus amyloliquefaciens by morphological observation and molecular data analysis, including 16SrDNA and gyraseA (gyrA) gene sequences. Antifungal substances of the isolate were extracted and purified by silica gel column chromatography, thin layer chromatography, and high performance liquid chromatography. The heat and UV ray stable compound was identified as iturin, a lipopeptide (LP). The isolate CNU114001 showed broad spectrum activity against 12 phytopathogenic fungi by dual culture method. The semi purified compound significantly inhibits the mycelial growth of pathogenic fungi (Alternaria panax, Botrytis cinera, Colletotrichum orbiculare, Penicillium digitatum, Pyricularia grisea and Sclerotica sclerotiorum) at 200 ppm concentration. Spore germ tube elongation of Botrytis cinerea was inhibited by culture filtrate of the isolate. Crude antifungal substance showed antagonistic activity against cucumber scleotiorum rot in laboratory, and showed antagonistic activity against tomato gray mold, cucumber, and pumpkin powdery mildew in greenhouse condition. [ABSTRACT FROM AUTHOR]

Previous studies have reported that KIOM-79 shows a strong inhibitory effect on AGE formation and inhibited a proinflammatory state in a murine macrophage cell line. In the present study, we investigated the effect of KIOM-79 on AGE accumulation and vascular inflammation in the aorta of Zucker diabetic fatty (ZDF) rats, a commonly used model of type 2 diabetes. Sevenweek- old male ZDF rats were treated with KIOM-79 (50 mg/kg) once a day orally for 13 weeks. We examined the dissected aortas for AGE accumulation, expression of the receptor for AGEs (RAGE), and the expression of proinflammatory factors, including monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and vascular adhesion molecule-1 (VCAM-1). Nuclear factor-kappaB (NF-κB) and inducible nitric oxide synthase (iNOS) were also measured by Southwestern histochemistry, electrophoretic mobility shift assay (EMSA), and immunohistochemistry, respectively. KIOM-79 markedly reduced the accumulation of AGEs and the expression of RAGE in the aorta. We also found that KIOM-79 attenuated the expression of inflammatory factors including NF-κB, MCP-1, VEGF, VCAM-1, and iNOS in the aortas of ZDF rats. These data suggest that KIOM-79 may prevent or retard the development of inflammation in diabetic vascular disease. [ABSTRACT FROM AUTHOR]

Compounds were isolated from a methanol extract of the dried stem barks of Viburnum sargentii Koehne. The structures of the compounds, namely 9′-O-methylvibsanol (3), furcatoside A (4) and lareciresinol (5) were elucidated by analysis of spectroscopic data and comparison with values for previously known analogues. In addition, (+)-catechin (1), (+)-epicatechin (2) were also isolated. This work also examined the cytotoxic effects of three compounds 3-5 (25-100 μM) in MCF-7 and A549 cells after 24, 48 and 72 h of exposure. Our results showed that 9′-O-methylvibsanol (3) exhibited strong concentration-dependent anticancer effects according to the MTT assay and produced morphological changes consistent with apoptosis, as confirmed by Ho3342 staining analysis revealed that more apoptotic cells were observed after 9′-O-methylvibsanol (3) treatment. [ABSTRACT FROM AUTHOR]

The receptor for advanced glycation end products (RAGE) and its ligands have been implicated in the activation of oxidant stress and inflammatory pathways in vascular smooth muscle cells (VSMCs) leading to the initiation and augmentation of atherosclerosis. Here we report that non-receptor Src tyrosine kinase and the membrane protein caveolin-1 (Cav-1) play a key role in the activation of RAGE by S100B in VSMCs. S100B increased the activation of Src kinase and tyrosine phosphorylation of caveolin-1 in VSMCs. A RAGE-specific antibody blocked both these effects. An inhibitor of Src kinase, PP2, significantly blocked S100B-induced activation of Src kinase, mitogen-activated protein kinases, transcription factors NF-κB and STAT3, superoxide production, tyrosine phosphorylation of Cav-1, VSMC migration, and expression of the pro-inflammatory genes monocyte chemotactic protein-1 and interleukin-6. Cholesterol depletion also inhibited S100-induced effects indicating the requirement for intact caveolae in RAGE-specific signaling. Nucleofection of either a Src dominant negative mutant, or a Cav-1 mutant lacking the scaffolding domain, or Cav-1 short hairpin RNA significantly reduced S100B-induced inflammatory gene expression in VSMCs. Furthermore, VSMCs derived from insulin-resistant and diabetic db/db mice displayed increased RAGE expression, Src activation, and migration compared with those from control db/+ mice. The RAGE antibody blocked enhanced migration in db/db cells. These studies demonstrate for the first time that, in VSMCs, Src kinase and Cav-1 play important roles in RAGE-mediated inflammatory gene expression and migration, key events associated with diabetic vascular complications. [ABSTRACT FROM AUTHOR]

Studies the biphasic regulation of plasminogen activator (PA)/inhibitor by low-density lipoprotein (LDL) in mesangial cells. Effect of LDL on extracellular matrix-associated antigen levels; Concentration-dependent effects of LDL on inhibition of PA activity; Effect of LDL on tissue type PA release in human mesangial cells.