Abstract Food-grade titanium dioxide (TiO 2 ) containing a nanoscale particle fraction (TiO 2 -NPs) is approved as a white pigment (E171 in Europe) in common foodstuffs, including confectionary. ...There are growing concerns that daily oral TiO 2 -NP intake is associated with an increased risk of chronic intestinal inflammation and carcinogenesis. In rats orally exposed for one week to E171 at human relevant levels, titanium was detected in the immune cells of Peyer’s patches (PP) as observed with the TiO 2 -NP model NM-105. Dendritic cell frequency increased in PP regardless of the TiO 2 treatment, while regulatory T cells involved in dampening inflammatory responses decreased with E171 only, an effect still observed after 100 days of treatment. In all TiO 2 -treated rats, stimulation of immune cells isolated from PP showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased. E171 or NM-105 for one week did not initiate intestinal inflammation, while a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model. These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO 2 from dietary sources.
Food-grade titanium dioxide (TiO
) containing a nanoscale particle fraction (TiO
-NPs) is approved as a white pigment (E171 in Europe) in common foodstuffs, including confectionary. There are growing ...concerns that daily oral TiO
-NP intake is associated with an increased risk of chronic intestinal inflammation and carcinogenesis. In rats orally exposed for one week to E171 at human relevant levels, titanium was detected in the immune cells of Peyer's patches (PP) as observed with the TiO
-NP model NM-105. Dendritic cell frequency increased in PP regardless of the TiO
treatment, while regulatory T cells involved in dampening inflammatory responses decreased with E171 only, an effect still observed after 100 days of treatment. In all TiO
-treated rats, stimulation of immune cells isolated from PP showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased. E171 or NM-105 for one week did not initiate intestinal inflammation, while a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model. These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO
from dietary sources.
The use of Alloc group in SPPS for the
N
α
protection of amino acids is an alternative to the Boc and Fmoc protecting groups. The smooth removal of Alloc group in neutral conditions with catalytic ...amounts of Pd(PPh
3)
4 in the presence of PhSiH
3 as a scavenger for the allyl system permits orthogonality with the most common protecting groups. Furthermore, a tandem deprotection-coupling reaction allows the suppression of DKP formation in cases where this side reaction is troublesome.
The use of Alloc group in SPPS for the
N
α
protection of amino acids is an alternative to the Boc and Fmoc protecting groups. The smooth removal of Alloc group in neutral conditions with catalytic amounts of Pd(PPh
3P)
4 in the presence of PhSiH
3 as scavenger of the allyl system makes this group orthogonal with the most common protecting groups. A tandem deprotection-coupling reaction allow the suppression of DKP in cases where this side reaction is troublesome.
reaction: see text A new strategy for SPPS in the reverse direction based on the use of 2-Cl-trityl resin, an allyl ester as the temporary protecting group, and Cu(OBt)(2)/DIPCDI or HATU/DIEA as the ...coupling method is described. These conditions ensure good yields with minimal racemization of the C-terminal residue.
Graphic
Allyl carboxylates, carbamates and phenoxides may be cleaved or transacylated in the presence of palladium catalyst and either phenyltrihydrosilane or ...N-methyl-N-(trimethylsilyl)-trifluoroacetamide. These reactions are totally compatible with the presence of Boc and, as far as phenyltrihydrosilane is concerned, Fmoc protections.
N
α-allyloxycarbonyl derivatives of amino acids undergo smooth coupling with various carboxy-activated partners when treated with phenylsilane (PhSiH
3) in the presence of catalytic amounts of ...tetrakis-(triphenylphosphine) palladium.
Graphic
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