Background and purpose:
5α,8α‐Epidioxy‐22E‐ergosta‐6, 22‐dien‐3β‐ol (ergosterol peroxide) is a major antitumour sterol produced by edible or medicinal mushrooms. However, its molecular mechanism of ...action has yet to be determined. Here, we examine the anticancer and anti‐inflammatory effects of ergosterol peroxide.
Experimental approach:
After treating RAW264.7 macrophages with LPS and purified ergosterol peroxide or ergosterol, we determined LPS‐induced inflammatory cytokines, nuclear DNA binding activity of transcription factors and phosphorylation of MAP kinases (MAPKs). HT29 colorectal adenocarcinoma cells were treated with ergosterol peroxide for 5 days. To investigate the antitumour properties of ergosterol peroxide, we performed DNA microarray and RT‐PCR analyses and determined the reactive oxygen species (ROS) in HT29 cells.
Key results:
Ergosterol peroxide suppressed LPS‐induced TNF‐α secretion and IL‐1α/β expression in RAW264.7 cells. Ergosterol peroxide and ergosterol suppressed LPS‐induced DNA binding activity of NF‐κB and C/EBPβ, and inhibited the phosphorylation of p38, JNK and ERK MAPKs. Ergosterol peroxide down‐regulated the expression of low‐density lipoprotein receptor (LDLR) regulated by C/EBP, and HMG‐CoA reductase (HMGCR) in RAW264.7 cells. In addition, ergosterol peroxide showed cytostatic effects on HT29 cells and increased intracellular ROS. Furthermore, ergosterol peroxide induced the expression of oxidative stress‐inducible genes, and the cyclin‐dependent kinase inhibitor CDKN1A, and suppressed STAT1 and interferon‐inducible genes.
Conclusion and Implication:
Our results suggest that ergosterol peroxide and ergosterol suppress LPS‐induced inflammatory responses through inhibition of NF‐κB and C/EBPβ transcriptional activity, and phosphorylation of MAPKs. Moreover, ergosterol peroxide appears to suppress cell growth and STAT1 mediated inflammatory responses by altering the redox state in HT29 cells.
British Journal of Pharmacology (2007) 150, 209–219. doi:10.1038/sj.bjp.0706972
Nitrification, a key process in the global nitrogen cycle that generates nitrate through microbial activity, may enhance losses of fertilizer nitrogen by leaching and denitrification. Certain plants ...can suppress soil-nitrification by releasing inhibitors from roots, a phenomenon termed biological nitrification inhibition (BNI). Here, we report the discovery of an effective nitrification inhibitor in the root-exudates of the tropical forage grass Brachiaria humidicola (Rendle) Schweick. Named "brachialactone," this inhibitor is a recently discovered cyclic diterpene with a unique 5-8-5-membered ring system and a γ-lactone ring. It contributed 60-90% of the inhibitory activity released from the roots of this tropical grass. Unlike nitrapyrin (a synthetic nitrification inhibitor), which affects only the ammonia monooxygenase (AMO) pathway, brachialactone appears to block both AMO and hydroxylamine oxidoreductase enzymatic pathways in NITROSOMONAS: Release of this inhibitor is a regulated plant function, triggered and sustained by the availability of ammonium (NHFormula: see text) in the root environment. Brachialactone release is restricted to those roots that are directly exposed to NHFormula: see text. Within 3 years of establishment, Brachiaria pastures have suppressed soil nitrifier populations (determined as amoA genes; ammonia-oxidizing bacteria and ammonia-oxidizing archaea), along with nitrification and nitrous oxide emissions. These findings provide direct evidence for the existence and active regulation of a nitrification inhibitor (or inhibitors) release from tropical pasture root systems. Exploiting the BNI function could become a powerful strategy toward the development of low-nitrifying agronomic systems, benefiting both agriculture and the environment.
Abstract Potential contribution from gamma-ray sources to the Galactic diffuse gamma rays observed above 100 TeV (sub-PeV energy range) by the Tibet AS γ experiment is an important key to ...interpreting recent multimessenger observations. This paper reveals a surprising fact: none of the 23 Tibet AS γ diffuse gamma-ray events above 398 TeV within the Galactic latitudinal range of ∣ b ∣ < 10° come from the 43 sub-PeV gamma-ray sources reported in the 1LHAASO catalog, which proves that these sources are not the origins of the Tibet AS γ diffuse gamma-ray events. No positional overlap between the Tibet AS γ diffuse gamma-ray events and the sub-PeV LHAASO sources currently supports the diffusive nature of the Tibet AS γ diffuse gamma-ray events, although their potential origin in the gamma-ray sources yet unresolved in the sub-PeV energy range cannot be ruled out.
The O antigen constitutes the outermost part of the lipopolysaccharide layer in Gram-negative bacteria. The chemical composition and structure of the O antigen show high levels of variation even ...within a single species revealing itself as serological diversity. Here, we present a complete sequence set for the O-antigen biosynthesis gene clusters (O-AGCs) from all 184 recognized Escherichia coli O serogroups. By comparing these sequences, we identified 161 well-defined O-AGCs. Based on the wzx/wzy or wzm/wzt gene sequences, in addition to 145 singletons, 37 serogroups were placed into 16 groups. Furthermore, phylogenetic analysis of all the E. coli O-serogroup reference strains revealed that the nearly one-quarter of the 184 serogroups were found in the ST10 lineage, which may have a unique genetic background allowing a more successful exchange of O-AGCs. Our data provide a complete view of the genetic diversity of O-AGCs in E. coli showing a stronger association between host phylogenetic lineage and O-serogroup diversification than previously recognized. These data will be a valuable basis for developing a systematic molecular O-typing scheme that will allow traditional typing approaches to be linked to genomic exploration of E. coli diversity.
We report on the analysis of the 10-1000 TeV large-scale sidereal anisotropy of Galactic cosmic rays (GCRs) with the data collected by the Tibet Air Shower Array from 1995 October to 2010 February. ...In this analysis, we improve the energy estimate and extend the decl. range down to −30°. We find that the anisotropy maps above 100 TeV are distinct from that at a multi-TeV band. The so-called tail-in and loss-cone features identified at low energies get less significant, and a new component appears at ∼100 TeV. The spatial distribution of the GCR intensity with an excess (7.2 pre-trial, 5.2 post-trial) and a deficit (−5.8 pre-trial) are observed in the 300 TeV anisotropy map, in close agreement with IceCube's results at 400 TeV. Combining the Tibet results in the northern sky with IceCube's results in the southern sky, we establish a full-sky picture of the anisotropy in hundreds of TeV band. We further find that the amplitude of the first order anisotropy increases sharply above ∼100 TeV, indicating a new component of the anisotropy. All these results may shed new light on understanding the origin and propagation of GCRs.
Pneumococcal serotype replacement is an important issue after the introduction of pneumococcal conjugate vaccine (PCV) in children. After the introduction of 13-valent PCV, the incidence of invasive ...pneumococcal diseases (IPD) caused by Streptococcus pneumoniae serotype 12F (Sp12F) have increased in some countries; however, an outbreak of Sp12F has not reported in the post-13-valent PCV era. We experienced a local outbreak of Sp12F during March through May 2016 in Tsuruoka city, Japan after the introduction of 13-valent PCV in 2013. The IPD patients were two children and seven adults, three of whom died with a rapid disease progress. Although the clear transmission route was not determined, eight of the nine patients (89%) had close contact with children, which suggests that transmitted colonisation of Sp12F among children and adults might be the source of transmission. Continuous monitoring of IPDs, along with the determination of pneumococcal serotypes, is warranted in the post-13-valent PCV era. New IPD control strategies may be needed if this fatal outbreak continues to occur.
For research on cosmic gamma rays with energies in the range of several tens of teraelectronvolts or more, we investigated a method to improve the angular resolution of an air shower. In an air ...shower, the density of secondary gamma rays is several times higher than that of electrons and those measurement is important for determining the shower direction. It was found that the angular resolution in the shower front-fit method decreases in inverse proportion to the square root of the number of measured particles. Even if the total number of measured particles is the same, secondary gamma rays contribute more to the improvement of angular resolution than electrons. If secondary gamma rays could be measured at an altitude of 4,740 m with a sensitivity of 100 %, an improvement of approximately 40 % was determined for a 500 TeV shower. A water Cherenkov detector with high gamma-ray sensitivity was investigated through Monte Carlo simulation. Detection efficiencies of approximately 0.38 and 0.76 were obtained for vertically incident gamma rays and electrons, respectively, using 19 8-inch diameter PMTs inside a detector installed in a water tank of radius 4.5 m and water depth 1.6 m. The detection time error for secondary gamma rays is approximately 2.18 ns at an incident angle of 0
∘
and the standard error in the detection time for shower front particles was found to be approximately 10 times lower than that obtained by using a plastic scintillation detector with an area of 1 m
2
.
Based on genome mining, a new antibacterial peptide named actinokineosin was isolated from a rare actinomycete Actinokineospora spheciospongiae. The amino acid sequence of the C‐terminus of ...actinokineosin was established by TOF‐MS/MS experiments. The amino acid sequence in the macrolactam ring was determined by TOF‐MS/MS analyses after cleavage with BNPS‐skatole and successive trypsin treatment. As a result of an antibacterial assay using a paper disk, actinokineosin showed antibacterial activity against Micrococcus luteus at a dosage of 50 μg per disk. From the genome sequence data of A. spheciospongiae, the biosynthetic gene cluster of actinokineosin was found and was indicated to consist of 10 genes. Among the genes, the gene aknA encoded the precursor of actinokineosin and the genes including aknC, aknB1 and aknB2 were proposed as modification enzymes to give mature actinokineosin.
Significance and Impact of the Study
Genome mining is a powerful tool to find new bioactive compounds from the genome database. In this report, we succeeded in isolation and structure determination of a new antibacterial peptide named actinokineosin based on genome mining.
Significance and Impact of the Study: Genome mining is a powerful tool to find new bioactive compounds from the genome database. In this report, we succeeded in isolation and structure determination of a new antibacterial peptide named actinokineosin based on genome mining.
Highlights ► Thrombin activates MAPK and primary-cultured rat microglia. ► Sesamin suppresses the activation of p44/42 MAPK and cultured microglia. ► Hemorrhagic neuron injury is involved in ...activated p44/42 MAPK and microglia. ► Sesamin suppresses the activation of p44/42 MAPK and microglia in vivo . ► Sesamin confers neuroprotection.
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