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A major objective of 'omics' technologies is to understand genetic causality of complex traits of human diseases. High-throughput omics technologies and their application to medicine open up remarkable opportunities for realising optimised medical treatment for individuals. Because many major breakthrough and discoveries in this field have been driven by the development of new omics technologies, in this review, the authors aim to provide an in-depth description of their underlying principles as a foundation of developing another new omics technology, and to introduce their emerging applications for personalised medicine. The systems biology approach is then introduced as a future direction towards actionable personalised medicine. [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.

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]

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]

Background: Accumulating evidences suggest that aldose reductase (AR) inhibitors and advanced glycation end product (AGE) formation inhibitors may prevent chronic hyperglycemia-induced long-term complication in diabetes. Transforming growth factor-beta1 (TGF-β1) plays an important role in the development of diabetic nephropathy. Allium species have been utilized in folk medicine throughout the world for the treatment of various physical disorders. However, the benefits of Allium victorialis (A. victorialis) against diabetic complications, especially nephropathy, have yet to be explored. In the present study, we investigated the protective effect of the compounds isolated from A. victorialis leaf on diabetic nephropathy. Methods: In vitro AR activity, AGEs formation, and AGE-receptor for AGEs (RAGE) binding in human RAGE (hRAGE)-overexpressing cells were tested. High glucose-induced transforming growth factor-beta1 (TGF-β1) expression was also examined in mouse kidney mesangial cells (MMCs) cultured under high glucose. Results: Of the isolated eight compounds from A. victorialis leaf extracts tested, quercitrin exhibited the most pronounced inhibitory effects on AR activity (IC50 value of 0.17 µM) and AGEs formation (IC50 value of 4.20 µM). Furthermore, quercitrin disrupted AGE-RAGE binding in a concentration-dependent manner in hRAGE-overexpressing cells. Additionally, of the eight compounds tested, ferulic acid significantly reduced high glucose-induced TGF-β1 expression and secretion in MMCs. Conclusions: Our results suggest that active compounds isolated from A. victorialis leaf exhibit inhibitory effects on AR activity in rat lenses and AGE formation. Further, ferulic acid reduces TGF-β1 mRNA expression and secretion in MMCs under diabetic conditions. Thus, A. victorialis is a good candidate for the development of treatments for diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Background: Obesity causes metabolic disease and is a serious health problem around the world. Polygonum cuspidatum (POCU1b) has been used clinically for the treatment of constipation, gallstones, hepatitis, and inflammation in East Asian countries. The principal aim of this study was to investigate for the first time whether the extract of Polygonum cuspidatum (POCU) biologically affects adipogenesis in 3 T3-L1 preadipocytes. Methods: Fractions (n-hexan, ethyl acetate, n-butanol, and water) of POCU ethanol extract were evaluated in vitro for their inhibitory activities on pancreatic lipase. Of the fractions, the n-butanol of POCU ethanol extract (POCU1b) was examined anti-obesity activity in 3 T3-L1 preadipocytes. To examine the inhibitory effect of POCU1b on adipogenesis, 3 T3-L1 preadipocytes were treated every the other day with POCU1b at various concentrations (0 ~ 25 μg/mL) for twelve days. Oil-red O staining and triglyceride content assay were performed to determine the lipid accumulation. The expression of mRNA and proteins associated lipid accumulation was measured using RT-PCR and Western blotting analysis. We also examined the effect of POCU1b on level of phosphorylated AMP-activated protein kinase (pAMPK) in 3 T3-L1 preadipocytes with POCU1b at various concentrations during adipocyte differentiation. Results: POCU1b exhibited the most pronounced inhibitory effects on pancreatic lipase activity. We found that POCU1b inhibited adipocyte differentiation in 3 T3-L1 preadipocytes in a dose-dependent manner, as evidenced by the reduced formation of lipid droplets and decreased glycerol-3-phosphate dehydrogenase (GPDH) activity. We also showed that the expression levels of adipocyte differentiation-related protein (ADRP) and perilipin (a protein that coats lipid droplets in adipocytes) were both reduced after POCU1b treatment. Peroxisome proliferatoractivated receptor-gamma (PPAR-γ) and CCAAT/enhancer-binding protein-alpha (C/EBP-α) proteins, both major adipogenic transcription factors, were markedly reduced by POCU1b. Moreover, ADRP, perilipin, C/EBP-α, and PPAR-γ mRNA levels were also reduced by POCU1b. Levels of phosphorylated AMP-activated protein kinase (pAMPK) were elevated after POCU1b treatment (5, 10, and 25) in a dose-dependent manner. Conclusions: Taken together, these results suggest that the anti-obesity effects of POCU1b involve the inhibition of pancreatic lipase activity and adipogenesis via the down-regulation of lipid accumulation. [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]

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]

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]

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]

Transgenic chloroplasts have become attractive systems for heterologous gene expressions because of unique advantages. Here, we report a feasibility study for producing the nontoxic B subunit of Escherichia coli heat-labile enterotoxin (LTB) via chloroplast transformation of tobacco. Stable site-specific integration of the LTB gene into chloroplast genome was confirmed by PCR and genomic Southern blot analysis in transformed plants. Immunoblot analysis indicated that plant-derived LTB protein was oligomeric, and dissociated after boiling. Pentameric LTB molecules were the dominant molecular species in LTB isolated from transgenic tobacco leaf tissues. The amount of LTB protein detected in transplastomic tobacco leaf was approximately 2.5% of the total soluble plant protein, approximately 250-fold higher than in plants generated via nuclear transformation. The GM1–ELISA binding assay indicated that chloroplast-synthesized LTB protein bound to GM1-ganglioside receptors. LTB protein with biochemical properties identical to native LTB protein in the chloroplast of edible plants opens the way for inexpensive, safe, and effective plant-based edible vaccines for humans and animals. [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.

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.

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]

Summary

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]