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Background Bifidobacterium longum subsp. infantis ( B. infantis ) is a commensal bacterium that colonizes the gastrointestinal tract of breast-fed infants. B. infantis can efficiently utilize the abundant supply of oligosaccharides found in human milk (HMO) to help establish residence. We hypothesized that metabolites from B. infantis grown on HMO produce a beneficial effect on the host. Results In a previous study, we demonstrated that B. infantis routinely dominated the fecal microbiota of a breast fed Bangladeshi infant cohort (1). Characterization of the fecal metabolome of binned samples representing high and low B. infantis populations from this cohort revealed higher amounts of the tryptophan metabolite indole-3-lactic acid (ILA) in feces with high levels of B. infantis . Further in vitro analysis confirmed that B. infantis produced significantly greater quantities of the ILA when grown on HMO versus lactose, suggesting a growth substrate relationship to ILA production. The direct effects of ILA were assessed in a macrophage cell line and intestinal epithelial cell lines. ILA (1-10 mM) significantly attenuated lipopolysaccharide (LPS)-induced activation of NF-kB in macrophages. ILA significantly attenuated TNF-α- and LPS-induced increase in the pro-inflammatory cytokine IL-8 in intestinal epithelial cells. ILA increased mRNA expression of the aryl hydrogen receptor (AhR)-target gene CYP1A1 and nuclear factor erythroid 2–related factor 2 (Nrf2)-targeted genes glutathione reductase 2 (GPX2), superoxide dismutase 2 (SOD2), and NAD(P) H dehydrogenase (NQO1). Pretreatment with either the AhR antagonist or Nrf-2 antagonist inhibited the response of ILA on downstream effectors. Conclusions These findings suggest that ILA, a predominant metabolite from B. infantis grown on HMO and elevated in infant stool high in B. infantis , and protects gut epithelial cells in culture via activation of the AhR and Nrf2 pathway.

Cruciferous vegetables are gaining importance as nutritious and sustainable foods, rich in phytochemical compounds such as glucosinolates (GSLs). However, the breakdown products of these sulfur-based compounds, mainly represented by isothiocyanates (ITC) and indoles, can contribute to human health. In the human digestive system, the formation of these compounds continues to varying extents in the different stages of digestion, due to the contact of GSLs with different gastric fluids and enzymes under the physicochemical conditions of the gastrointestinal tract. Therefore, the aim of the present work was to uncover the effect of gastrointestinal digestion on the release of glucosinolates and their transformation into their bioactive counterparts by applying a simulated in vitro static model on a range of brassica (red radish, red cabbage, broccoli, and mustard) sprouts. In this sense, significantly higher bioaccessibility of ITC and indoles from GSLs of red cabbage sprouts was observed in comparison with broccoli, red radish, and mustard sprouts, due to the aliphatic GSLs proportion present in the different sprouts. This indicates that the bioaccessibility of GSLs from Brasicaceae sprouts is not exclusively associated with the initial content of these compounds in the plant material (almost negligible), but also with the release of GSLs and the ongoing breakdown reactions during the gastric and intestinal phases of digestion, respectively. Additionally, aliphatic GSLs provided higher bioaccessibility of their corresponding ITC in comparison to indolic and aromatic GSLs.

[Display omitted] •Three case reports in the context of synthetic cannabinoids are presented.•Post mortem femoral blood concentrations are reported.•Femoral blood concentrations cannot be correlated directly with the cause of death.•Every fatality involving synthetic cannabinoids should be assessed on a case by case basis. The use of synthetic cannabinoids (SC) has been widespread in certain groups of drug users for many years. In the scientific literature many intoxication cases and a number of fatalities after the use of synthetic cannabinoids were reported. In this paper three death cases are described with involvement of the synthetic cannabinoids 5F-PB-22, AB-CHMINACA, and 5F-ADB. The three cases occurred in the eastern region of Germany, which is known as a region of high methamphetamine abuse. All decedents were male, between 25 and 41 years old, and had a known history of drug use. Femoral blood concentrations of the synthetic cannabinoids were measured using a validated LC–MS/MS method. The concentration of 5F-PB-22 in the first case was 0.37ng/mL, the concentration of AB-CHMINACA in the second case was approximately 4.1ng/mL (extrapolated) and the 5F-ADB concentration in the third case was 0.38ng/mL. Compared to other published cases the concentrations in the here presented cases seem to be in the lower range. However, taking into account the scene of death, the results of the forensic autopsy and the full toxicological analysis, the deaths can be explained as a direct consequence of consumption of synthetic cannabinoids, although in case one and two relevant amounts of ethanol were found, and in case three trimipramine and olanzapine were present in non-toxic concentrations. It has to be noted that concentrations of synthetic cannabinoids in femoral blood cannot directly be judged as toxic or lethal due to the possibility of postmortem redistribution and the development of tolerance after frequent use. Therefore, all available information has to be considered carefully before stating SC use as the cause of death.

The consumption of synthetic cannabinoids (SCs) has significantly increased in the last decade and the analysis of SCs and their metabolites in human specimens is gaining interest in clinical and forensic toxicology. A pilot study has been carried out using a combination of an initial last generation gas chromatography-mass spectrometry (GC-MS) screening method for the determination of JWH-122, JWH-210, UR-144) in oral fluid (OF) of consumers and an ultra-high performance liquid chromatography high resolution mass spectrometry (UHPLC-HRMS) confirmatory method for the quantification of the parent compounds and their metabolites in the same biological matrix. OF samples were simply liquid-liquid extracted before injecting in both chromatographic systems. The developed methods have been successfully validated and were linear from limit of quantification (LOQ) to 50 ng/mL OF. Recovery of analytes was always higher than 70% and matrix effect always lower than 15% whereas intra-assay and inter-assay precision and accuracy were always better than 16%. After smoking 1 mg JWH-122 or UR-144 and 3 mg JWH-210, maximum concentration of 4.00–3.14 ng/mL JWH-122, 8.10–7.30 ng/mL JWH-210 ng/mL and 7.40 and 6.81 ng/mL UR-144 were measured by GC-MS and UHPLC-HRMS respectively at 20 min after inhalation. Metabolites of JWH 122 and 210 were quantified in OF by UHPLC-HRMS, while that of UR144 was only detectable in traces. Our results provide for the first time information about disposition of these SCs and their metabolites in consumers OF. Last generation GC-MS has proven useful tool to identify and quantify parent SCs whereas UHPLC-HRMS also confirmed the presence of SCs metabolites in the OF of SCs consumers.

A direct enantio- and chemo-selective high-performance liquid chromatographic method was developed for determining the enantiomeric impurity of the chiral active pharmaceutical ingredient silodosin. The simultaneous separation of enantiomers of silodosin and its main organic related substances listed in the Japanese Pharmacopoeia (JP) monograph for drug substance was achieved on Chiralpak AD-3 (250 mm × 4.6 mm, 3 μm) column under normal-phase isocratic conditions. The optimized conditions employed the mixture n-heptane-ethanol-diethylamine (70:30:0.1) (v/v/v) as a mobile phase and a temperature of 35 °C. The complete separation of the enantiomers of silodosin and its main impurities was obtained within 12 min. The chromatographic method has been validated according to the International Conference on Harmonization (ICH) guidelines and compared with the method reported in the JP monograph. The standard curve for silodosin exhibited linearity (R2 > 0.999) within the concentration range of 1.13–2500 µg mL−1. The Chiralpak AD-3 has demonstrated a remarkable level of efficiency, enabling the attainment of limits of quantitation for silodosin of 1.13 µg mL−1 (equivalent to 0.057% of a sample solution of 2 mg mL−1) and ranging from 0.48 µg mL−1 to 1.94 µg mL−1 for other impurities.

•Fatal intoxication involving synthetic cannabinoid MDMB-CHMICA is presented.•MDMB-CHMICA was revealed in ante- and postmortem blood and internal organs tissues.•Synthetic cannabinoids concentrations and effects are discussed.•The presented case shows the health risks associated with MDMB-CHMICA use. MDMB-CHMICA is a synthetic cannabinoid that appeared on the European drug market in September 2014. This substance was found in Poland in the herbal mixture “Mocarz” (“Strongman”), which caused a large outbreak of intoxications at the beginning of July 2015. This paper describes the circumstances of death and toxicological findings in a fatal intoxication with MDMB-CHMICA (in combination with alcohol). Loss of consciousness and asystole occurred a few minutes after smoking the ‘legal high’. The man died after 4 days of hospitalisation. The cause of death accepted by the medical examiner was multiple organ failure. MDMB-CHMICA was detected and quantified in blood (ante- and postmortem) and internal organs tissues. The samples were analysed using liquid chromatography with mass spectrometry (LC-MS/MS). The concentration of MDMB-CHMICA in antemortem blood was 5.6ng/mL. Although the death occurred after 4 days from administration a relatively high concentration (2.6ng/g) was estimated in the brain. Traces of this compound were also found in other postmortem materials (blood, stomach, liver, bile, and kidney). The presented case shows the health risks associated with MDMB-CHMICA use. The administration of this substance can lead to the number of organ failures, cardiac arrest and consequently death.

Chemopreventive properties of Brassica vegetables are attributed mainly to their characteristic compounds—glucosinolates (GLs) and their main hydrolysis products—isothiocyanates (ITCs) and indoles. In this study, we compared antiproliferative activity (MTT test in HT29 cells) and genotoxic effects (comet assay in HT29 cells and restriction analysis in a cell-free system) of three GLs (sinigrin (SIN), glucotropaeolin (GTL), and glucobrassicin (GLB)) with that of their major degradation products. Intact GLs did not exhibit cytotoxic activity, possibly due to their limited bioavailability. However, in the presence of myrosinase (MYR), GLs gained the ability to inhibit HT29 cells’ growth. The addition of MYR caused the hydrolysis of GLs to the corresponding ITCs or indoles, i.e. compounds that show stronger biological activity than parent GLs. Pure ITC/indole solutions showed the strongest antiproliferative activity. Based on the results of restriction analysis, it was found that GLs to a greater extent than ITCs caused DNA modification in a cell-free system. In the case of GLs, metabolic activation by the S9 fraction increased this effect, and at the same time changed the preferential binding site from the area of base pairs AT to GC base pairs. Of all compounds tested, only benzyl ITC caused DNA damage detectable in the comet assay, but it required relatively high concentrations.

Aedes albopictus is a vector of dengue, chikungunya, and dirofilariasis. Volatile compounds are crucial for mosquitoes to locate their hosts. This knowledge has allowed the identification of attractants derived from human odours for highly anthropophilic mosquito species. In this study, we used rats as a experimental model to identify potential attractants for host-seeking Ae. albopictus females. Porapak Q extracts from immature female rats were more attractive to Ae. albopictus females than those from mature and pregnant females, and males. Phenol, 4-methylphenol, 4-ethylphenol, and indole were identified compounds in male, immature, mature, and pregnant female extracts. There were quantitative differences in these compounds among the extracts that likely explain the discrepancy in their attractiveness. Ae. albopictus females were not attracted to the single compounds when was compared with the four-component blend. However, the binary blend of 4-methylphenol  + 4-ethylphenol and the tertiary blend of 4-methylphenol + 4-ethylphenol + indole were as attractive as the four-component blend. In the field trials, BGS traps baited with the tertiary or quaternary blends caught more Ae. albopictus females and males than BGS traps without lures. This is the first laboratory and field study to identify compounds that mediate the attraction of Ae . albopictus to one of its hosts.

Cyanobacterial blooms have become a serious problem in Lake Taihu during the last 20 years, and Microcystis aeruginosa and Synechococcus sp. are the two dominant species in cyanobacterial blooms of Lake Taihu. A freshwater bacterial strain, Shewanella sp. Lzh-2, with strong algicidal properties against harmful cyanobacteria was isolated from Lake Taihu. Two substances with algicidal activity secreted extracellularly by Shewanella sp. Lzh-2, S-2A and S-2B, were purified from the bacterial culture of strain Lzh-2 using ethyl acetate extraction, column chromatography, and high performance liquid chromatography (HPLC) in turn. The substances S-2A and S-2B were identified as hexahydropyrrolo[1,2-a]pyrazine-1,4-dione and 2, 3-indolinedione (isatin), respectively, based on liquid chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS), and hydrogen-nuclear magnetic resonance (H-NMR) analyses, making this the first report of their algicidal activity toward cyanobacteria. S-2A (hexahydropyrrolo[1,2-a]pyrazine-1,4-dione) had no algicidal effects against Synechococcus sp. BN60, but had a high level of algicidal activity against M. aeruginosa 9110. The LD50 value of S-2A against M. aeruginosa 9110 was 5.7 μg/ml. S-2B (2, 3-indolinedione) showed a potent algicidal effect against both M. aeruginosa 9110 and Synechococcus sp. BN60, and the LD50 value of S-2B against M. aeruginosa 9110 and Synechococcus sp. BN60 was 12.5 and 34.2 μg/ml, respectively. Obvious morphological changes in M. aeruginosa 9110 and Synechococcus sp. BN60 were observed after they were exposed to S-2A (or S-2B) for 24 h. Approximately, the algicidal activity, the concentration of S-2A and S-2B, and the cell density of Lzh-2 were positively related to each other during the cocultivation process. Overall, these findings increase our knowledge about algicidal substances secreted by algicidal bacteria and indicate that strain Lzh-2 and its two algicidal substances have the potential for use as a bio-agent in controlling cyanobacterial blooms in Lake Taihu.

Odor from buildings where pigs are housed is generated by anaerobic fermentation of undigested materials in pig slurry stored for several weeks in pit. The objective of this study was to investigate the effect of storage period on the level of odorous compounds in pig slurry and on its bacterial community. A slurry sample (15 L) was taken from the pit of a finisher pig building and incubated in acryl chambers for six- weeks. Slurry for analysis was sampled every two-week. Levels of odorous compounds in the slurry sample were drastically changed after two weeks of storage period; levels of phenols and short chain fatty acids (SCFAs) were decreased (P<0.05), whereas indoles and branched-chain fatty acids (BCFAs) were increased (P<0.05). Among dominant bacteria, Bacteroides and Porphyromonadacese_uc_g revealed a strong positive correlation with the levels of phenols and SCFAs. Populations of AC160630_g, Acholeplasmatales_uc_g, Mollicutes_uc_g and Cloacamonas_f_uc_g positively correlated with indole and BCFAs content. Taken together, levels of odorous compounds were increased after two weeks of storage, possibly because of changes in the predominant bacterial groups to those that use protein as a carbon source in the hypo-carbohydrate conditions.