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The article presents a study on the correlation between antioxidative activities and metabolite changes in a traditional soybean fermentation product, Cheonggukjang (CGJ). It investigated the metabolite changes during the CGJ fermentation and evaluated its effects which have employed the use of liquid chromatography mass spectrometry and multivariate analysis. The study is said to be the first to indicate a correlation between antioxidant effects and metabolites during CGJ fermentation process.

The article focuses on the use of Aspergillus kawachii, Aspergillus oryzae, and Rhizopus species for the fermentation of rice Koji. It states that principal component analysis was conducted to distinguish metabolite patterns based on fungi species. Meanwhile, metabolite changes were correlated with enzyme activities associated with glycolysis. Results show that production of time-dependent metabolites can be a tool in determining rice koji's inoculant fungi and optimal fermentation time.

The article presents a study which examines the metabolite profiling of Cheonggukjang inoculated with various Bacillus strains such as Bacillus amyloliqueciens CH86-1, Bacillus licheniformis 58 and Bacillus licheniformis 67 during fermentation. It says that metabolite profiling was made using gas chromatography-mass spectrometry (GC-MS) combined with multivariate analysis. It explores the effects of Bacillus strains on the profiles of metabolites including amino acids, sugar, and organic acids.

Escherichia coli cells expressing Rhodococcus DK17 o-xylene dioxygenase genes were used for bioconversion of m-xylene. Gas chromatography–mass spectrometry analysis of the oxidation products detected 3-methylbenzylalcohol and 2,4-dimethylphenol in the ratio 9:1. Molecular modeling suggests that o-xylene dioxygenase can hold xylene isomers at a kink region between α6 and α7 helices of the active site and α9 helix covers the substrates. m-Xylene is unlikely to locate at the active site with a methyl group facing the kink region because this configuration would not fit within the substrate-binding pocket. The m-xylene molecule can flip horizontally to expose the meta-position methyl group to the catalytic motif. In this configuration, 3-methylbenzylalcohol could be formed, presumably due to the meta effect. Alternatively, the m-xylene molecule can rotate counterclockwise, allowing the catalytic motif to hydroxylate at C-4 yielding 2,4-dimethylphenol. Site-directed mutagenesis combined with structural and functional analyses suggests that the alanine-218 and the aspartic acid-262 in the α7 and the α9 helices play an important role in positioning m-xylene, respectively. [ABSTRACT FROM AUTHOR]

DOX–magnetic PLGA nanoparticles conjugated with well-tailored antibodies were synthesized for the detection and therapy of breast cancer. Magnetic nanocrystals embedded in polymeric nanoparticles did not inhibit the nanoparticle formulation or drug release kinetics. The multimodal nanoparticles demonstrated remarkable cancer cell affinity and ultrasensitivity via magnetic resonance imaging. Furthermore, the loaded anticancer drugs were released and sustained for three weeks. [ABSTRACT FROM AUTHOR]

We identified a p-cumate degrading gene cluster (designated cmt) with a novel organization in our genomic studies of the terpene-degrading Rhodococcus sp. strain T104. The mutant strain SN140, isolated for the inability to grow on p-cumate, accumulates 2,3-dihydroxy- p-cumate as identified by liquid chromatography-mass spectrometry and 300 MHz proton nuclear magnetic resonance spectroscopy. Reverse transcriptase polymerase chain reaction experiments showed that the cmt genes are operonic and induced specifically by growth on p-cumate. This report is the first example of identifying the genes for p-cumate degradation in a gram-positive organism based on functional data. [ABSTRACT FROM AUTHOR]

We cloned lipG, which encoded a lipolytic enzyme, from a Korean tidal fiat metagenomic library. LipG was related to six putative lipases previously identified only in bacterial genome sequences. These enzymes comprise a new family. We partially characterized LipG, providing the first experimental data for a member of this family. [ABSTRACT FROM AUTHOR]

Uric acid is the end product of the purine degradation pathway in humans. It is catabolized to allantoin by urate oxidase or uricase (E.C. 1.7.3.3.) in most vertebrates except humans, some primates, birds, and certain species of reptiles. Here we provide evidence that mouse transthyretin-related protein facilitates the hydrolysis of 5-hydroxyisourate, the end product of the uricase reaction. Mutagenesis experiments showed that the residues that are absolutely conserved across the TRP family, including His11, Arg51, His102, and the Cterminal Tyr-Arg-Gly-Ser, may constitute the active site of mTRP. Based on these results, we propose that the transthyretin-related proteins present in diverse organisms are not functionally related to transthyretin but actually function as hydroxyisourate hydrolases. [ABSTRACT FROM AUTHOR]

α-Synuclein is the major constituent of Lewy bodies, a pathological signature of Parkinson disease, found in the degenerating dopaminergic neurons of the substantia nigra pars compacta. Amyloidosis generating the insoluble fibrillar protein deposition has been considered to be responsible for the cell death observed in the neurodegenerative disorder. In order to develop a controlling strategy toward the amyloid formation, 1,1′-(1,10-decanediyl)-bis-[4-a-mino-2-methylquinolinium] (dequalinium), was selected and examined in terms of its specific molecular interaction with α-synuclein. The protein was self-oligomerized by dequalinium, which gave rise to the ladder formation on N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine/SDS-PAGE in the presence of a coupling reagent of N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline. The double-headed structure of dequalinium with the two cationic 4-aminoquinaldinium rings was demonstrated to be critical for the protein self-oligomerization. The dequalinium-binding site was located on the acidic C-terminal region of the protein with an approximate dissociation constant of 5.5 μM. The protein self-oligomerization induced by the compound has resulted in the protofibril formation of α-synuclein before it has developed into amyloids. The protofibrils were demonstrated to affect the membrane intactness of liposomes, and they have also been shown to influence cell viability of human neuroblastoma cells. In addition, dequalinium treatment of the α-synuclein-overexpressing cells exerted a significant cell death. Therefore, it is pertinent to consider that dequalinium could be used as a molecular probe to assess toxic mechanisms related to the amyloid formation of α-synuclein. Ultimately, the compound could be employed to develop therapeutic and preventive strategies toward a-synucleinopathies including Parkinson disease. [ABSTRACT FROM AUTHOR]

In many Gram-negative bacteria, including a number of pathogens such as Pseudomonas aeruginosa and Erwinia carotovora, virulence factor production and biofilm formation are linked to the quorum-sensing systems that use diffusible N-acyl-L-homoserine lactones (AHLs) as intercellular messenger molecules. A number of organisms also contain genes coding for lactonases that hydrolyze AHLs into inactive products, thereby blocking the quorum-sensing systems. Consequently, these enzymes attract intense interest for the development of antiinfection therapies. However, the catalytic mechanism of AHL-lactonase is poorly understood and subject to controversy. We here report a 2.0-Å resolution structure of the AHL-lactonase from Bacillus thuringiensis and a 1.7-Å crystal structure of its complex with L-homoserine lactone. Despite limited sequence similarity, the enzyme shows remarkable structural similarities to glyoxalase II and RNase Z proteins, members of the metallo-β-lactamase superfamily. We present experimental evidence that AHL-lactonase is a metalloenzyme containing two zinc ions involved in catalysis, and we propose a catalytic mechanism for bacterial metallo-AHL-lactonases. [ABSTRACT FROM AUTHOR]

The metabolically versatile Rhodococcus sp. strain DK17 utilizes indan as a growth substrate via the o-xylene pathway. Metabolite and reverse transcription-PCR analyses indicate that o-xylene dioxygenase hydroxylates indan at the 4,5 position of the aromatic moiety to form cis-indan-4,5-dihydrodiol, which is dehydrogenated to 4,5-indandiol by a dehydrogenase. 4,5-Indandiol undergoes ring cleavage by a meta-cleavage dioxygenase. [ABSTRACT FROM AUTHOR]

Abstract During the COVID-19 pandemic, facemasks played a pivotal role in preventing person-person droplet transmission of viral particles. However, prolonged facemask wearing causes skin irritations colloquially referred to as ‘maskne’ (mask + acne), which manifests as acne and contact dermatitis and is mostly caused by pathogenic skin microbes. Previous studies revealed that the putative causal microbes were anaerobic bacteria, but the pathogenesis of facemask-associated skin conditions remains poorly defined. We therefore characterized the role of the facemask-associated skin microbiota in the development of maskne using culture-dependent and -independent methodologies. Metagenomic analysis revealed that the majority of the facemask microbiota were anaerobic bacteria that originated from the skin rather than saliva. Previous work demonstrated direct interaction between pathogenic bacteria and antagonistic strains in the microbiome. We expanded this analysis to include indirect interaction between pathogenic bacteria and other indigenous bacteria classified as either ‘pathogen helper (PH)’ or ‘pathogen inhibitor (PIn)’ strains. In vitro screening of bacteria isolated from facemasks identified both strains that antagonized and promoted pathogen growth. These data were validated using a mouse skin infection model, where we observed attenuation of symptoms following pathogen infection. Moreover, the inhibitor of pathogen helper (IPH) strain, which did not directly attenuate pathogen growth in vitro and in vivo, functioned to suppress symptom development and pathogen growth indirectly through PH inhibitory antibacterial products such as phenyl lactic acid. Taken together, our study is the first to define a mechanism by which indirect microbiota interactions under facemasks can control symptoms of maskne by suppressing a skin pathogen.

With increasing interest in Korean foods and beverages, Korean traditional alcoholic beverages need to be studied. To characterize Korean traditional alcoholic beverages, we analyzed the metabolites of Takju, Yakju, and Traditional-Soju using 48 commercial products. We performed non-targeted metabolite profiling using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and identified 33 significantly discriminant metabolites, including nine organic acids, three amino acids, and seven fatty acids, in the three types of alcoholic beverage. Subsequently, we quantified the profiled metabolites in each product and compared their contents to identify alcoholic beverage type-specific metabolites. Thus, we figured out seven metabolites using receiver operating characteristic (ROC) curves. The results revealed that octadecanoic acid (limit of detection (LOD) to 168.72 mg/L), nonanoic acid (LOD to 112.54 mg/L), and octanoic acid (8.00 to 145.08 mg/L) in Takju; succinic acid (LOD to 1.90 mg/mL), heptanoic acid (LOD to 343.23 mg/L), and hexadecanoic acid (20.28 to 126.45 mg/L) in Yakju; and malonic acid (LOD to 19.13 mg/mL) in Traditional-Soju, with an area under the curve (AUC) > 0.7, are important metabolites that can distinguish the type of alcoholic beverage. Our results provide qualitative and quantitative metabolite information about Korean traditional alcoholic beverages that can be used by consumers and manufacturers.

Probiotic fermentation of plant-based materials can lead to the generation of various bioactive substances via bacterial metabolites and the biotransformation of phenolic compounds. We compared the metabolic differences between fermentation by Limosilactobacillus fermentum KCTC15072BP (LFG) and fermentation by Lactiplantibacillus plantarum KGMB00831 (LPG) in guava leaf extract (0%, 0.5%, and 2% (w/v))-supplemented medium via non-targeted metabolite profiling. By performing multivariate statistical analysis and comparing the different guava leaf extract groups, 21 guava-derived and 30 bacterial metabolites were identified. The contents of guava-derived glucogallin, gallic acid, and sugar alcohols were significantly higher in LFG than they were in LPG. Similarly, significantly higher contents of guava-derived pyrogallol, vanillic acid, naringenin, phloretin, and aromatic amino acid catabolites were obtained with LPG than with LFG. LFG led to significantly higher antioxidant activities than LPG, while LPG led to significantly higher antiglycation activity than LFG. Interestingly, the fermentation-induced increase in the guava-leaf-extract-supplemented group was significantly higher than that in the control group. Thus, the increased bioactivity induced by guava fermentation with the Lactobacillaceae strain may be influenced by the synergistic effects between microbial metabolites and plant-derived compounds. Overall, examining the metabolic changes in plant-based food fermentation by differentiating the origin of metabolites provides a better understanding of food fermentation.

Cutibacterium acnes, one of the most abundant skin microbes found in the sebaceous gland, is known to contribute to the development of acne vulgaris when its strains become imbalanced. The current limitations of acne treatment using antibiotics have caused an urgent need to develop a systematic strategy for selectively targeting C. acnes, which can be achieved by characterizing their cellular behaviors under various skin environments. To this end, we developed a genome-scale metabolic model (GEM) of virulent C. acnes, iCA843, based on the genome information of a relevant strain from ribotype 5 to comprehensively understand the pathogenic traits of C. acnes in the skin environment. We validated the model qualitatively by demonstrating its accuracy prediction of propionate and acetate production patterns, which were consistent with experimental observations. Additionally, we identified unique biosynthetic pathways for short-chain fatty acids in C. acnes compared to other GEMs of acne-inducing skin pathogens. By conducting constraint-based flux analysis under endogenous carbon sources in human skin, we discovered that the Wood-Werkman cycle is highly activated under acnes-associated skin condition for the regeneration of NAD, resulting in enhanced propionate production. Finally, we proposed potential anti-C. acnes targets by using the model-guided systematic framework based on gene essentiality analysis and protein sequence similarity search with abundant skin microbiome taxa.

Context: Pinus densiflora Siebold & Zucc. (Pinaceae) needle extracts ameliorate oxidative stress, but research into their anti-inflammatory effects is limited. Objective: To investigate antioxidant and anti-inflammatory effects of a Pinus densiflora needles (PINE) ethanol extract in vitro and in vivo. Materials and methods: We measured levels of reactive oxygen species (ROS), superoxide dismutase (SOD) and inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW264.7 cells at various PINE concentrations (25, 50 and 100 lg/mL; but 6.25, 12.5 and 25 lg/mL for interleukin-1b and prostaglandin E2 (PGE2)). Thirty ICR mice were randomized to six groups: vehicle, control, PINE pre-treatment (0.1, 0.3 and 1 mg/left ear for 10 min followed by arachidonic acid treatment for 30 min) and dexamethasone. The posttreatment ear thickness and myeloperoxidase (MPO) activity were measured. Results: PINE 100 lg/mL significantly decreased ROS (IC50, 70.93 lg/mL, p<0.01), SOD (IC50, 30.99 lg/mL, p<0.05), malondialdehyde (p<0.01), nitric oxide (NO) (IC50, 27.44 lg/mL, p<0.01) and tumour necrosis factor-alpha (p<0.05) levels. Interleukin-1b (p<0.05) and PGE2 (p<0.01) release decreased significantly with 25 lg/mL PINE. PINE 1mg/ear inhibited LPS-stimulated expression of cyclooxygenase-2 and inducible NO synthase in RAW264.7 macrophages and significantly inhibited ear oedema (36.73-15.04% compared to the control, p<0.01) and MPO activity (167.94-105.59%, p<0.05). Discussion and conclusions: PINE exerts antioxidant and anti-inflammatory effects by inhibiting the production of inflammatory mediators. Identified flavonoids such as taxifolin and quercetin glucoside can be attributed to effect of PINE. [ABSTRACT FROM AUTHOR]

Plant extracts including secondary metabolites have anti-inflammatory and anti-obesity activities. This study was conducted to investigate the anti-obesity properties of fermented Artemisia annua (AW) and Salicornia herbacea (GW) in vitro and in mice. The metabolite profiling of AW and GW extracts was performed using UHPLC−LTQ−Orbitrap–MS/MS, and gene expression was analyzed using real-time PCR for adipocyte difference factors. The anti-obesity effects in mice were measured using serum AST, ALT, glucose, TG, and cholesterol levels. Metabolites of the plant extracts after fermentation showed distinct differences with increasing anti-obesity active substances. The efficacy of inhibitory differentiation adipogenesis of 3T3-L1 adipocytes was better for GW than AW in a concentration-dependent manner. RT-PCR showed that the GW extract significantly reduced the expression of genes involved in adipocyte differentiation and fat accumulation (C/EBPα, PPARγ, and Fas). In C57BL/6 mice fed the HFD, the group supplemented with AW and GW showed reduced liver weight, NAS value, and fatty liver by suppressing liver fat accumulation. The GW group significantly reduced ALT, blood glucose, TG, total cholesterol, and LDL-cholesterol. This study displayed significant metabolite changes through biotransformation in vitro and the increasing anti-obesity effects of GW and AW in mice. GW may be applicable as functional additives for the prevention and treatment of obesity.

Although α-synuclein is the main structural component of the insoluble filaments that form Lewy bodies in Parkinson disease (PD), its physiological function and exact role in neuronal death remain poorly understood. In the present study, we examined the possible functional relationship between α-synuclein and several forms of matrix metalloproteinases (MMPs) in the human dopaminergic neuroblastoma (SK-N-BE) cell line. When SK-N-BE cells were transiently transfected with α-synuclein, it was secreted into the extracellular culture media, concomitantly with a significant decrease in cell viability. Also the addition of nitric oxide-generating compounds to the cells caused the secreted α-synuclein to be digested, producing a small fragment whose size was similar to that of the fragment generated during the incubation of α-synuclein with various MMPs in vitro. Among several forms of MMPs, α-synuclein was cleaved most efficiently by MMP-3, and MALDI-TOF mass spectra analysis showed that α-synuclein is cleaved from its C-terminal end with at least four cleavage sites within the non-Aβ component of AD amyloid sequence. Compared with the intact form, the protein aggregation of α-synuclein was remarkably facilitated in the presence of the proteolytic fragments, and the fragment-induced aggregates showed more toxic effect on cell viability. Moreover, the levels of MMP-3 were also found to be increased significantly in the rat PD brain model produced by the cerebral injection of 6-hydroxydopamine into the substantia nigra. The present study suggests that the extracellularly secreted α-synuclein could be processed via the activation of MMP-3 in a selective manner. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) alters metabolism during the gastric carcinogenesis process. This study aimed to determine the metabolites in the gastric mucosa according to the status of the H. pylori infection. Patients who visited the outpatient clinic for a gastroscopy and H. pylori tests were included. Gas chromatography–time-of-flight mass spectrometry (GC-TOF-MS) analysis was performed using gastric biopsied specimens from the corpus. Twenty-eight discriminative metabolites were found in the gastric mucosa of 10 patients with current H. pylori infection, in 15 with past infection, and in five with no infection history. The relative abundances (RAs) of amino acids and sugars/sugar alcohols were higher in patients with no infection history than in patients with current or past infection. The current infection group showed higher RAs of organic acids and lower RAs of fatty acids and lipids compared with the other groups. The RA of inosine was highest in the past infection group. Based on GC-TOF-MS analysis findings, metabolites differed not only between the infected and non-infected patients, but also between those with and without infection history. Amino acid and sugars/sugar alcohol metabolites decreased in patients with current or past infection, whereas fatty acid and lipid metabolites decreased only during current infection.

Though varying metabolomes are believed to influence distinctive characteristics of different soy foods, an in-depth, comprehensive analysis of both soluble and volatile metabolites is largely unreported. The metabolite profiles of different soy products, including cheonggukjang, meju, doenjang, and raw soybean, were characterized using LC-MS (liquid chromatography–mass spectrometry), GC-MS (gas chromatography–mass spectrometry), and headspace solid-phase microextraction (HS-SPME) GC-MS. Principal component analysis (PCA) showed that the datasets for the cheonggukjang, meju, and doenjang extracts were distinguished from the non-fermented soybean across PC1, while those for cheonggukjang and doenjang were separated across PC2. Volatile organic compound (VOC) profiles were clearly distinct among doenjang and soybean, cheonggukjang, and meju samples. Notably, the relative contents of the isoflavone glycosides and DDMP (2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one) conjugated soyasaponins were higher in soybean and cheonggukjang, compared to doenjang, while the isoflavone aglycones, non-DDMP conjugated soyasaponins, and amino acids were significantly higher in doenjang. Most VOCs, including the sulfur containing compounds aldehydes, esters, and furans, were relatively abundant in doenjang. However, pyrazines, 3-methylbutanoic acid, maltol, and methoxyphenol were higher in cheonggukjang, which contributed to the characteristic aroma of soy foods. We believe that this study provides the fundamental insights on soy food metabolomes, which determine their nutritional, functional, organoleptic, and aroma characteristics.

Annona muricata (AM) is evergreen plant of the Annonaceae family and known to have anticancer and antidiabetic effects. However, anti-diabetic mechanisms of AM extracts (AME) associated with hepatic glucose regulation and lipid metabolism remain unclear. In this study, we investigated the protective effect of AME extracted on hepatic damage in diabetic mice. Diabetes was induced by a high-fat diet with two-times streptozotocin (STZ) injection (60 mg/kg BW) in C57BL/6 male mice. The diabetic mice were daily administered with AME (50 or 100 mg/kg BW) by gavage for 9 weeks. Biomarkers related to energy metabolism and insulin signaling were examined to identify the effect of AME on hyperglycemia induced hepatic damage. AME supplementation reduced levels of FBG, HbA1c, HOMA-IR and hepatic lipid profiles as well as enhanced insulin signaling by increased the protein levels of IRS-1 accompanied GLUT2 in diabetic mice. Especially low dose of AME showed the beneficial effect of reducing oxidative stress (4-HNE, protein carbonyls, Nrf2, NQO1) and improved hepatic morphology demonstrated by lipid droplets along with upregulation of lipophagy (pAMPK, p-mTOR/mTOR, LC3-2/LC3-1) in diabetic mice. Moreover, AME supplementation ameliorated hepatic lipid metabolism (FAS, SREBP1c, C/EBPα, PPARγ, CPT1A, PPARα) and energy metabolism (pAMPK, PGC1α) in diabetic mice. Taken together, this study suggested that AME could be helpful to prevent hepatic abnormality by regulation of insulin signaling associated with energy metabolism and autophagy in diabetes.

Yams (Dioscorea spp.) are cultivated and consumed as edible tubers, while their leaves are discarded as waste or burned with negative environmental impact. Herein, the metabolites of two yam species (Danma, DAN; Dunggeunma, DUN), harvested in June, July, and August, were profiled using GC-TOF-MS and UHPLC-LTQ-Orbitrap-MS/MS and the antioxidant activity of the extracts was evaluated to stimulate the utilization of yam leaves as a by-product. We observed that the relative levels of amino acids, organic acids, sugars, and saponins decreased linearly with prolonged harvest time, while fatty acid, phenanthrene, and flavonoid levels gradually increased. Furthermore, the leaf extracts obtained in August exhibited the highest antioxidant activity. To determine the antioxidant-contributing metabolites, OPLS-DA was performed for the leaf metabolites of DAN and DUN leaves harvested in August. Hydroxytyrosol-glucoside, apigenin-rhamnoside, and rutin were more abundant in DUN, while luteolin, phenanthrene derivatives, epicatechin, and kaempferide were relatively higher in DAN and their respective metabolites were positively correlated with the antioxidant activity. Moreover, secondary metabolites were more abundant in the leaves than in the roots, and consequently, the antioxidant activity of the former was also higher. Overall, the potential value of yam leaves as a renewable source of bioactive compounds is proposed.

Three types of doenjang, a fermented soybean paste, were prepared by adding coriander (CR), Korean mint (KM), and peppermint (PM) and compared to the control group (CN) by studying their metabolite profiles and antioxidant activities followed by different fermentation periods (1, 30, and 150 days, respectively). The primary metabolome was analyzed by GC-TOF-MS, and 36 of metabolites were identified in four types of doenjang samples (CN, CR, KM, and PM). Samples were clustered based on the herb type and fermentation period in PCA and PLS-DA analysis. For the secondary metabolome analysis, UHPLC-Q-orbitrap-MS was used, and 26 metabolites were identified. The statistical analysis showed that the samples were clustered by herb type rather than fermentation period, and the samples containing KM and PM were located in the same group. The DPPH assay showed that PM-containing doenjang had the highest antioxidant activity. Correlation analysis indicated that organic acids such as lactic acid, malonic acid, succinic acid, uracil, vanillic acid, and quinic acid showed positive correlation with the DPPH activity. Overall, our results demonstrated that incorporating herbs in doenjang during fermentation caused significant shifts (p-value < 0.05) in the doenjang metabolites and antioxidant activity. Hence, herbs could be utilized for enhancing doenjang fermentation.

Numerous varieties of doenjang are manufactured by many food companies using different ingredients and fermentation processes, and thus, the qualities such as taste and flavor are very different. Therefore, in this study, we compared many products, specifically, 19 traditional doenjang (TD) and 17 industrial doenjang (ID). Subsequently, we performed non-targeted metabolite profiling, and multivariate statistical analysis to discover distinct metabolites in two types of doenjang. Amino acids, organic acids, isoflavone aglycones, non-DDMP (2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4- one) soyasaponins, hydroxyisoflavones, and biogenic amines were relatively abundant in TD. On the contrary, contents of dipeptides, lysophospholipids, isoflavone glucosides and DDMP-conjugated soyasaponin, precursors of the above-mentioned metabolites, were comparatively higher in ID. We also observed relatively higher antioxidant, protease, and β-glucosidase activities in TD. Our results may provide valuable information on doenjang to consumers and manufacturers, which can be used while selecting and developing new products.

Ultraviolet B (UV-B) light, as a physical elicitor, can promote the secondary metabolites biosynthesis in plants. We investigated effects of different energy levels of UV-B radiation on growth and bioactive compounds of Crepidiastrum denticulatum. Three-week-old seedlings were grown in a plant factory for 5 weeks. Plants were subjected to different levels of UV-B (0, 0.1, 0.25, 0.5, 1.0, and 1.25 W m−2), 6 h a day for 6 days. All UV-B treatments had no negative effect on the shoot dry weight; however, relatively high energy treatments (1.0 and 1.25 W m−2) inhibited the shoot fresh weight. UV-B light of 0.1, 0.25, and 0.5 W m−2 did not affect total chlorophyll and H2O2 contents; however, they increased total carotenoid content. On 4 days, 0.25 W m−2 treatment increased antioxidant capacity, total hydroxycinnamic acids (HCAs) content, and several sesquiterpenes. Treatments with 1.0 and 1.25 W m−2 increased total carotenoid, total HCAs, and H2O2 contents, and destroyed chlorophyll pigments, reducing maximum quantum yield of photosystem II and causing visible damage to leaves. Partial least squares discrimination analysis (PLS-DA) showed that secondary metabolites were distinguishably changed according to energy levels of UV-B. The potential of 0.25 W m−2 UV-B for the efficient production of bioactive compounds without growth inhibition in C. denticulatum was identified.

Objective: Our previous study revealed that chronic consumption of a high-fat diet (HFD) stimulates colon cancer progression in obesity-resistant BALB/c mice. The aim of the present study was to investigate the significant alteration of metabolites caused by tumor progression and an HFD in the serum and liver in the same mouse model. Methods: Male BALB/c mice were fed either a control diet or a HFD for 20.5 wk. The syngeneic CT26 colon carcinoma cells were injected into the right rear flank of mice after 16 wk of feeding. Metabolites in serum and liver samples were analyzed by ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry-based metabolomics. Results: HFD feeding and tumor injection induced changes in the choline-containing phospho-lipids, namely, phosphatidylcholines and lysophosphatidylcholines (lysoPCs), and lysophosphati-dylethanolamines in the serum and liver. The majority of these metabolite changes were due to HFD feeding (11 in sera and 5 in livers) rather than tumors (3 in sera and 1 in livers). Conclusion: The HFD- and tumor-related metabolite alterations of phospholipids, especially lysoPCs, in the liver and serum of obesity-resistant mice, suggesting that the lysoPCs are potential biomarkers for the chronic consumption of HFD in nonobese individuals. [ABSTRACT FROM AUTHOR]

Haginin A, an isoflav-3-ens isolated from the branch of Lespedeza cyrtobotrya, is almost unknown. Here, we report that haginin A exhibits a strong hypopigmentary effect in Melan-a cells and significantly inhibits melanin synthesis. Haginin A shows potent inhibitory effects with an IC50 (half-maximal inhibitory concentration) value of 5.0 μM on mushroom tyrosinase activity, and functioned as a noncompetitive inhibitor. Also, haginin A decreased microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein-1 (TRP-1) protein production. To identify the signaling pathway of haginin A, the ability of haginin A to influence extracellular signal-regulated protein kinase (ERK) and Akt/protein kinase B (PKB) activation was investigated. Apparently, haginin A induced ERK and Akt/PKB in a dose-dependent manner. In addition, the specific inhibition of the ERK and the Akt/PKB signaling pathways by PD98059 and LY294002, respectively, increased melanin synthesis. Furthermore, haginin A decreased UV-induced skin pigmentation in brown guinea-pigs. Also, haginin A presented remarkable inhibition on the body pigmentation in the zebrafish model system and decreased tyrosinase activity. Together, haginin A is an effective inhibitor of hyperpigmentation caused by UV irradiation or by pigmented skin disorders through downregulation via ERK and Akt/PKB activation, MITF, and also by the subsequent downregulation of tyrosinase and TRP-1 production.Journal of Investigative Dermatology (2008) 128, 1227–1235; doi:10.1038/sj.jid.5701177; published online 22 November 2007 [ABSTRACT FROM AUTHOR]

Polymyxin, a long-known peptide antibiotic, has recently been reintroduced in clinical practice because it is sometimes the only available antibiotic for the treatment of multidrug-resistant gram-negative pathogenic bacteria. Lack of information on the biosynthetic genes of polymyxin, however, has limited the study of structure-function relationships and the development of improved polymyxins. During whole genome sequencing of Paenibacillus polymyxa E681, a plant growth-promoting rhizobacterium, we identified a gene cluster encoding polymyxin synthetase. Here, we report the complete sequence of the gene cluster and its function in polymyxin biosynthesis. The gene cluster spanning the 40.6-kb region consists of five open reading frames, designated pmxA, pmxB, pmxC, pmxD, and pmxE. The pmxC and pmxD genes are similar to genes that encode transport proteins, while pmxA, pmxB, and pmxE encode polymyxin synthetases. The insertional disruption of pmxE led to a loss of the ability to produce polymyxin. Introduction of the pmx gene cluster into the amyE locus of the Bacillus subtilis chromosome resulted in the production of polymyxin in the presence of extracellularly added L-2,4-diaminobutyric acid. Taken together, our findings demonstrate that the pmx gene cluster is responsible for polymyxin biosynthesis. [ABSTRACT FROM AUTHOR]