The aim was to assess the role of probiotics in oral health maintenance among patients undergoing fixed orthodontic therapy (OT). An unrestricted search of indexed databases was performed until April 2020 using the following Mesh-terms: (1) probiotic and (2) orthodontic. Randomized controlled clinical trials (RCTs) evaluating the influence of probiotic therapy (PT) towards oral health maintenance/improvement in patients undergoing fixed OT were included. Data screening, selection, and extraction were performed; and the risk of bias was assessed using the Cochrane Collaboration’s tool. All evaluations were performed by 2 independent researchers; and disagreements were resolved via discussion. Nine RCTs were included. Eight studies reported that PT improves oral health in patients undergoing fixed OT. Seven studies showed that PT reduces the counts of oral pathogenic bacteria in the oral biofilm and/or saliva. One study reported that PT reduces halitosis in patients undergoing fixed OT. One study found that PT reduces the scores of plaque index (PI) and gingival index (GI); and one study reported that PT has no significant influence on PI and GI in patients undergoing fixed OT. One study reported that PT does not prevent the formation of white spot lesions during fixed OT. Three and 6 studies had a moderate and low risk of bias, respectively. A power analysis was performed in 4 studies. In conclusion, probiotics exhibit antimicrobial activity against oral pathogenic bacteria; however, due to the limitations of the studies assessed, further well-designed RCTs are needed.
CD1d-restricted invariant natural killer T (iNKT) cells play a critical role in the induction of airway hyperreactivity (AHR). After intranasal alpha-galactosylceramide (α-GalCer) administration, bronchoalveolar lavage fluid (BALF) proteins from mouse lung were resolved by two-dimensional differential gel electrophoresis (2D-DIGE), and identified by tandem mass spectroscopy. A lack of iNKT cells prevented the development of airway responses including AHR, neutrophilia and the production of the proinflammatory cytokines in lungs. Differentially abundant proteins in the BALF proteome of α-GalCer-treated wild type mice included lungkine (CXCL15), pulmonary surfactant-associated protein D (SFTPD), calcium-activated chloride channel regulator 1 (CLCA1), fragments of complement 3, chitinase 3-like proteins 1 (CH3LI) and 3 (CH3L3) and neutrophil gelatinase-associated lipocalin (NGAL). These proteins may contribute to iNKT regulated AHR via several mechanisms: altering leukocyte chemotaxis, increasing airway mucus production and possibly via complement activation. 相似文献
We describe a new anseriform bird from the late Oligocene of Saint-André, Marseille, in southern France. Saintandreachenoides, gen. et sp. nov. is the first avian species reported from the locality, which is well known for its mammalian fossils. The new species belongs to the extinct Romainvilliinae and represents the latest occurrence of the taxon, which was before only known from the late Eocene and early Oligocene of Europe. S.chenoides is also the largest species of Romainvilliinae and increases the known morphological diversity of the taxon. The identification of a goose-sized representative of the Romainvilliinae in the late Oligocene of Europe raises the possibility that some of the large late Paleogene or early Neogene Anseriformes with uncertain phylogenetic affinities also belong to this taxon. 相似文献
Haemoglobin I from Lucina pectinata is a monomeric protein consisting of 142 amino acids. Its active site contains a peculiar arrangement of phenylalanine residues (PheB10, PheCD1 and PheE11) and a distal Gln at position E7. Active site mutations at positions B10, E7 and E11 were performed in deoxy haemoglobin I (HbI), followed by 10 ns molecular dynamic simulations. The results showed that the mutations induced changes in domains far from the active site producing more flexible structures than the native HbI. Distance analyses revealed that the heme pocket amino acids at positions E7 and B10 are extremely sensitive to any heme pocket residue mutation. The high flexibility observed by the E7 position suggests an important role in the ligand binding kinetics in ferrous HbI, while both positions play a major role in the ligand stabilisation processes. Furthermore, our results showed that E11Phe plays a pivotal role in protein stability. 相似文献
With the aim to provide sensitive 31P NMR probes of intra- and extracellular pH gradients that may reach cellular acidic compartments in biological systems, new alpha-aminophosphonates were designed to meet basic requirements such as a low pK(a)s and a great chemical difference (Deltadelta(ab)) between the limiting 31P NMR chemical shifts in acidic (delta(a)) and basic (delta(b)) media. A series of six phosphorylated pyrrolidines and linear aminophosphonates were synthesized using aminophosphorylation reactions and were screened for cytotoxicity on cultured Müller cells. Among the compounds not being toxic under these conditions, three molecules were selected since they displayed the best in vitro (in several phosphate buffers and in a cytosol-like solution) properties as 31P NMR acidic pH markers, that is 3, 5 and 9, having the pK(a) values of 3.63, 5.89 and 5.66, respectively. The Deltadelta(ab) values of these pH markers were at least 3 times larger than that of standard 31P NMR probes, with a low sensitivity to ionic strength changes. From these data, it was proposed that 3, 5 and 9 could be used as reporting probes of subtle proton movements in acidic compartments, an area that still remains poorly investigated using non invasive 31P NMR methods. 相似文献
Lucina pectinata ctenidia harbor three heme proteins: sulfide-reactive hemoglobin I (HbI(Lp)) and the oxygen transporting hemoglobins II and III (HbII(Lp) and HbIII(Lp)) that remain unaffected by the presence of H(2)S. The mechanisms used by these three proteins for their function, including ligand control, remain unknown. The crystal structure of oxygen-bound HbII(Lp) shows a dimeric oxyHbII(Lp) where oxygen is tightly anchored to the heme through hydrogen bonds with Tyr(30)(B10) and Gln(65)(E7). The heme group is buried farther within HbII(Lp) than in HbI(Lp). The proximal His(97)(F8) is hydrogen bonded to a water molecule, which interacts electrostatically with a propionate group, resulting in a Fe-His vibration at 211 cm(-1). The combined effects of the HbII(Lp) small heme pocket, the hydrogen bonding network, the His(97) trans-effect, and the orientation of the oxygen molecule confer stability to the oxy-HbII(Lp) complex. Oxidation of HbI(Lp) Phe(B10) --> Tyr and HbII(Lp) only occurs when the pH is decreased from pH 7.5 to 5.0. Structural and resonance Raman spectroscopy studies suggest that HbII(Lp) oxygen binding and transport to the host bacteria may be regulated by the dynamic displacements of the Gln(65)(E7) and Tyr(30)(B10) pair toward the heme to protect it from changes in the heme oxidation state from Fe(II) to Fe(III). 相似文献
A sigma-2 receptor ligand siramesine induces lysosomal leakage and cathepsin-dependent death of cancer cells in vitro and displays potent anti-cancer activity in vivo. The mechanism by which siramesine destabilizes lysosomes is, however, unknown. Here, we show that siramesine induces a rapid rise in the lysosomal pH that is followed by lysosomal leakage and dysfunction. The rapid accumulation of siramesine into cancer cell lysosomes, its ability to destabilize isolated lysosomes, and its chemical structure as an amphiphilic amine indicate that it is a lysosomotropic detergent. Notably, siramesine triggers also a substantial Atg6- and Atg7-dependent accumulation of autophagosomes that is associated with a rapid and sustained inhibition of mammalian target of rapamycin complex 1 (mTORC1; an inhibitor of autophagy). Siramesine fails, however, to increase the degradation rate of long-lived proteins. Thus, the massive accumulation of autophagosomes is likely to be due to a combined effect of activation of autophagy signaling and decreased autophagosome turnover. Importantly, pharmacological and RNA interference-based inhibition of autophagosome formation further sensitizes cancer cells to siramesine-induced cytotoxicity. These data identify siramesine as a lysosomotropic detergent that triggers cell death via a direct destabilization of lysosomes and cytoprotection by inducing the accumulation of autophagosomes. Threrefore, the combination of siramesine with inhibitors of autophagosome formation appears as a promising approach for future cancer therapy. 相似文献
Cytochrome c oxidase couples reduction of dioxygen to water to translocation of protons over the inner mitochondrial or bacterial membrane. A likely proton acceptor for pumped protons is the Delta-propionate of heme a(3), which may receive the proton via water molecules from a conserved glutamic acid (E278 in subunit I of the Paracoccus denitrificans enzyme) and which receives a hydrogen bond from a conserved tryptophan, W164. Here, W164 was mutated to phenylalanine (W164F) to further explore the role of the heme a(3) Delta-propionate in proton translocation. FTIR spectroscopy showed changes in vibrations possibly attributable to heme propionates, and the midpoint redox potential of heme a(3) decreased by approximately 50 mV. The reaction of the oxidized W164F enzyme with hydrogen peroxide yielded substantial amounts of the intermediate F' even at high pH, which suggests that the mutation rearranges the local electric field in the binuclear center that controls the peroxide reaction. The steady-state proton translocation stoichiometry of the W164F enzyme dropped to approximately 0.5 H(+)/e(-) in cells and reconstituted proteoliposomes. Time-resolved electrometric measurements showed that when the fully reduced W164F enzyme reacted with O(2), the membrane potential generated in the fast phase of this reaction was far too small to account either for full proton pumping or uptake of a substrate proton from the inside of the proteoliposomes. Time-resolved optical spectroscopy showed that this fast electrometric phase occurred with kinetics corresponding to the transition from state A to P(R), whereas the subsequent transition to the F state was strongly delayed. This is due to a delay of reprotonation of E278 via the D-pathway, which was confirmed by observation of a slowed rate of Cu(A) oxidation and which explains the small amplitude of the fast charge transfer phase. Surprisingly, the W164F mutation thus mimics a weak block of the D-pathway, which is interpreted as an effect on the side chain isomerization of E278. The fast charge translocation may be due to transfer of a proton from E278 to a "pump site" above the heme groups and is likely to occur also in wild-type enzyme, though not distinguished earlier due to the high-amplitude membrane potential formation during the P(R)--> F transition. 相似文献