Atopic dermatitis (AD) is a public health concern and is increasing in prevalence in urban areas. Recent advances in sequencing technology have demonstrated that the development of AD not only associate with the skin microbiome but gut microbiota. Gut microbiota plays an important role in allergic diseases including AD. The hypothesis of the “gut-skin” axis has been proposed and the cross-talk mechanism between them has been gradually demonstrated in the research. Probiotics contribute to the improvement of the intestinal environment, the balance of immune responses, regulation of metabolic activity. Most studies suggest that probiotic supplements may be an alternative for the prevention and treatment of AD. This study aimed to discuss the effects of probiotics on the clinical manifestation of AD based on gut microbial alterations. Here we reviewed the gut microbial alteration in patients with AD, the association between gut microbiota, epidermal barrier, and toll-like receptors, and the interaction of probiotics and gut microbiota. The potential mechanisms of probiotics on alleviating AD via upregulation of epidermal barrier and regulation of immune signaling had been discussed, and their possible effective substances on AD had been explored. This provides the supports for targeting gut microbiota to attenuate AD.

Supramolecular bimetallic Ru(II)/Pt(II) complexes [(tpy)Ru(PEt(2)Ph)(BL)PtCl(2)](2+) and their synthons [(tpy)Ru(L)(BL)](n)()(+) (where L = Cl(-), CH(3)CN, or PEt(2)Ph; tpy = 2,2':6',2''-terpyridine; and BL = 2,2'-bipyrimidine (bpm) or 2,3-bis(2-pyridyl)pyrazine (dpp)) have been synthesized and studied by cyclic voltammetry, electronic absorption spectroscopy, mass spectral analysis, and (31)P NMR. The mixed-metal bimetallic complexes couple phosphine-containing Ru chromophores to a reactive Pt site. These complexes show how substitution of the monodentate ligand on the [(tpy)RuCl(BL)](+) synthons can tune the properties of these light absorbers (LA) and incorporate a (31)P NMR tag by addition of the PEt(2)Ph ligand. The redox potentials for the Ru(III/II) couples occur at values greater than 1.00 V versus the Ag/AgCl reference electrode and can be tuned to more positive potentials on going from Cl(-) to CH(3)CN or PEt(2)Ph (E(1/2) = 1.01, 1.55, and 1.56 V, respectively, for BL = bpm). The BL(0/-) couple at -1.03 (bpm) and -1.05 V (dpp) for [(tpy)Ru(PEt(2)Ph)(BL)](2+) shifts dramatically to more positive potentials upon the addition of the PtCl(2) moiety to -0.34 (bpm) and -0.50 V (dpp) for the [(tpy)Ru(PEt(2)Ph)(BL)PtCl(2)](2+) bridged complex. The lowest energy electronic absorption for these complexes is assigned as the Ru(d pi) --> BL(pi*) metal-to-ligand charge transfer (MLCT) transition. These MLCT transitions are tuned to higher energy in the monometallic synthons when Cl(-) is replaced by CH(3)CN or PEt(2)Ph (516, 452, and 450 nm, for BL = bpm, respectively) and to lower energy when Pt(II)Cl(2) is coordinated to the bridging ligand (560 and 506 nm for BL = bpm or dpp). This MLCT state displays a broad emission at room temperature for all the dpp systems with the [(tpy)Ru(PEt(2)Ph)(dpp)PtCl(2)](2+) system exhibiting an emission centered at 750 nm with a lifetime of 56 ns. These supramolecular complexes [(tpy)Ru(PEt(2)Ph)(BL)PtCl(2)](2+) represent the covalent linkage of TAG-LA-BL-RM assembly (TAG = NMR active tag, RM = Pt(II) reactive metal).

A novel catalyst has been synthesized in which a manganese-porphyrin unit is linked to two 2,2′-bipyridyl groups and two pentafluorophenyl groups in trans fashion on its four meso positions. Relative to a previous catalyst in which the manganese-porphyrin had four 2,2′-bipyridyl groups, the new catalyst, in the presence of Cu 2+ ions as coordinating linkers, catalyzes the oxidation of a steroid substrate with much better regioselectivity and higher turnover numbers.We have described hydroxylation of steroids by mimics of the enzyme cytochrome P-450 class. In our earliest examples we used metalloporphyrins carrying cyclodextrin groups to bind hydrophobic substrates in water. When the cyclodextrins were linked to p-phenylene groups attached to the porphyrin meso positions in catalyst 1, we saw highly selective hydroxylation at the C-6 alpha position of a steroid derivative 2 doubly-bound into the cyclodextrins ( Figure 1). 1 However, there were only about ten turnovers before the catalyst was itself oxidatively destroyed. When instead the phenylene linkers in the catalyst were replaced by tetrafluorophenylene groups in catalyst 3, we still saw hydroxylation selectively at C-6 alpha, but now with 187 turnovers before destruction of the catalyst (Figure 1). 2 That same perfluorinated catalyst was also able to hydroxylate the steroid in the C-9 alpha position when a substrate was hydrophobically bound to three cyclodextrins of the catalyst. 3There could be advantages in changing the mode of substrates/catalyst binding. Hydrophobic binding is somewhat ill-defined geometrically, and it is seen only in water solvent. We had used double metal-ion coordination to bind a substrate to a metalloporphyrin and a metallosalen, and had observed good selective epoxidation of the substrate. 4 Thus we used rb33@columbia.edu. (Figure 2). 5 However, the oxidation was not selective, with observed formation of six almost evenly distributed products, including 6. Moreover, the turnover number was only 5, low compared to the 187 turnovers we observed with catalyst 3. NIH Public AccessThe poor catalytic performance in this biomimetic study might result from two factors-the intrinsic reactivity and the oxidative stability of catalyst 4 are significantly lower compared with catalyst 3, and the nitrogen atoms from both the manganese porphyrin and the substrate are easily oxidized to N-oxides under the hydroxylation conditions. 6 Once N-oxides are formed, the nitrogens lose the ability to coordinate to the metal center. Indeed, we isolated an initial undesired substrate oxidation product, the bis N-oxide of 5 from the hydroxylation experiments before basic hydrolysis; 7 this was not further hydroxylated under the same conditions.To avoid the undesired substrate oxidation, we attached different metal ligands to the steroid, two α-phosphonoacetyl groups in substrate 7 (Figure 3). 8,9 When 7 was subjected to hydroxylation with iodosobenzene and the manganese porphyrin 4 in a mixture of H 2 O and tBuOH (1:1), products resulting from hyd...

Gut microbiome plays an essential role in asthma development, and probiotic-based manipulation of the gut microbiome has been proposed to prevent asthma. Although the preventive effect of Lactobacillus supplementation against allergies has been reported, the precise Lactobacillus species beneficial for effective prevention of asthma remain unidentified and the underlying mechanisms remain unclear. Therefore, we aimed to investigate the efficacy of oral administration of six Lactobacillus species and the mechanism underlying asthma prevention via gut microbiome modulation. We investigated the effects of oral administration of L. rhamnosus, L. fermentum, L. casei, L. gasseri, L. salivarius, and L. reuteri (five strains of each species) on asthma and gut microbiome of house dust mite (HDM)-treated murine models of asthma. Of these, L. reuteri administration was the most effective: it alleviated airway inflammation, decreased total IgE and HDM-IgG1, and reduced Th2-associated proinflammatory cytokines. Moreover, modulation of specific microbial genera by L. reuteri was more effective in asthma prevention than the modulation of the overall microbiota composition. Lactobacillus and Enterococcus were enriched after L. reuteri supplementation and were closely associated with total IgE and IL-13 production. Furthermore, L. reuteri specifically altered the gut microbial function toward butyrate generation. Thus, L. reuteri may reduce the risk of asthma development by modulating specific gut microbiota to improve the lung immune environment. Our study suggests a novel option for gut microbiome manipulation via L. reuteri supplementation for suppression of asthma and other allergic diseases.

No abstract

No abstract

No abstract

Gut microbial disturbance affects allergic diseases including asthma, atopic dermatitis (AD) via the aberrant immune response. Some Bifidobacterial species and strains have been reported to improve AD via modulating immune-microbe interactions in patients. However, the effective metabolites and mechanism of alleviating AD in bifidobacteria remain to be elucidated. This study aimed to explore the microbial metabolite and mechanism of Bifidobacterium longum to improve AD. Based on shotgun metagenomic sequencing and UHPLC Q-Exactive-MS targeted metabolic experiments in vitro and in vivo , we focused on tryptophan metabolism and indole derivatives, which are endogenous ligands for aryl hydrocarbon receptor (AHR). Indole-3-carbaldehyde (I3C), a tryptophan metabolite of B. longum CCFM1029 activated AHR-mediated immune signaling pathway to improve AD symptoms in animal and clinical experiments. B. longum CCFM1029 upregulated tryptophan metabolism and increased I3C to suppress aberrant T helper 2 type immune responses, but these benefits were eliminated by AHR antagonist CH223191. Furthermore, B. longum CCFM1029 reshaped gut microbial composition in AD patients, increased fecal and serum I3C, and maintained the abundance of Lachnospiraceae related to tryptophan metabolism of gut microbiota. The results suggested that based on the interactions of the gut-skin axis, B. longum CCFM1029 upregulated tryptophan metabolism and produced I3C to activate AHR-mediated immune response, alleviating AD symptoms. Indole derivates, microbial metabolites of tryptophan, may be the potential metabolites of bifidobacteria to alleviate AD via the AHR signaling pathway.