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SummaryBacillus catabolite control protein (CcpA) mediates carbon catabolite repression (CCR) by controlling expression of catabolite responsive (CR) genes or operons through interaction with catabolite responsive elements ( cre s) located within or outside of CR promoters. Here, we investigated how CcpA inhibits the transcription of CR promoters in vitro . CcpA has different affinities for different cre s, but this does not correlate with its ability to inhibit transcription. In the amyE promoter, which overlaps a CcpA binding site ( amyE cre centred at + + + + 4.5), CcpA does not prevent RNA polymerase (RNAP) binding to the promoter; it may even interact with RNAP. Inserting non-integral turns of helix (1.5 and 2.5) between the amyE promoter ( ----10 hexamer) and the amyE cre relieved CCR of amyE expression. In the xyl operon, despite the downstream location of its cre (a major cre centred at + + + + 130.5), CcpA blocked transcription initiation, not elongation (roadblock) at the site of the cre . Taken together, our results strongly suggest that CcpA requires interactions with RNAP to inhibit transcription.

Quercetin is known to inhibit tyrosinase activity and melanin production in melanocytes. However, several reports suggest that quercetin has different and opposite effects on melanogenesis. This study examined the precise effects of quercetin on melanogenesis using cell-free assay systems and melanocytes. Quercetin inhibited the monophenolase and diphenolase activities of tyrosinase, and melanin synthesis in cell-free assay systems. Quercetin induced mild stimulation of the tyrosinase activity and dihydroxyphenylalaminechrome tautomerase (TRP-2) expression but only at low concentrations (<20 μm) in B16F10 melanoma cells. In contrast, the addition of 50 μm quercetin to the cells led to a significant decrease in the activity and synthesis of tyrosinase, as well as a decrease in the expression of tyrosinase-related protein-1 and TRP-2 proteins, regardless of the presence or absence of α-melanocyte stimulating hormone (α-MSH). Quercetin also reduced the intracellular cAMP and the phosphorylated protein kinase A levels in α-MSH-stimulated B16F10 cells. Moreover, quercetin (20 μm) diminished the expression and activity of tyrosinase, and melanin content in cultured normal human epidermal melanocytes. These effects were not related to its cytotoxic action. Although the in vivo effects of quercetin are still unclear, these results suggest that quercetin could play important roles in controlling melanogenesis.

Although several studies have evaluated the inhibitory effect of probiotics on halitosis, findings are inconsistent. This systematic review and meta-analysis of randomized clinical trials (RCT) was conducted to summarize the evidence on the effect of probiotics on halitosis. RCT on any type of probiotic treatment with at least 2-week duration were identified through electronic databases (PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials) and hand searched between 1946 and January 17, 2017. Primary outcomes were organoleptic (OLT) scores and volatile sulfur compounds (VSC). Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated. Meta-analysis was conducted to synthesize the evidence. Of the 153 articles identified, three met the inclusion criteria. Meta-analysis revealed that OLT scores (SMD = - 1.93, 95% CI - 2.85 to - 1.02, P < 0.0001) were significantly lower in subjects who received probiotics than in placebo groups, but no significant difference was observed at the VSC concentration (SMD = - 0.02, 95% CI - 2.12 to 2.07, P = 0.98). Current evidence is supportive of recommending probiotics for the management of halitosis. Based on this review, transient (average of 2 weeks) dosing with probiotics (mainly Lactobacillus strains) has a moderate effect on halitosis regarding OLT scores, but we could not confirm the effects of probiotics on the VSC reduction. The available evidence is quantitatively and qualitatively insufficient for further recommendations, especially with regard to administration strategies and pretreatment. Future studies should aim for longer follow-up and standardized administration methods to prove or refute the effect of probiotics on halitosis.

Transforming growth factor β (TGF-β) signaling has been implicated in dentin formation and repair; however, the molecular mechanisms underlying dentin formation remain unclear. To address the role of TGF-β signaling in dentin formation, we analyzed odontoblast-specific Tgfbr2 conditional knockout mice. The mutant mice had aberrant teeth with thin dysplastic dentin and pulpal obliteration, similar to teeth from human patients with dentinogenesis imperfecta type II and dentin dysplasia. In mutant, the odontoblasts lost their cellular polarity, and matrix secretion was disrupted after mantle dentin formation. As a consequence, the amount of predentin decreased significantly, and an ectopic fibrous matrix was formed below the odontoblast layer. This matrix gradually calcified and obliterated the pulp chamber with increasing age. Immunohistochemistry revealed decreased expression of alkaline phosphatase in mutant odontoblasts. In mutant dentin, Dsp expression was reduced, but Dmp1 expression increased significantly. Collagen type I, biglycan, and Dsp were expressed in the ectopic matrix. These results suggest that loss of responsiveness to TGF-β in odontoblasts results in impaired matrix formation and pulpal obliteration. Our study indicates that TGF-β signaling plays an important role in dentin formation and pulp protection. Furthermore, our findings may provide new insight into possible mechanisms underlying human hereditary dentin disorders and reparative dentin formation.

The simplest possible ACV morphometric information provided a statistically significant explanation of the portion of skeletal-maturation variability not dependent on chronological age. These results verify that ACV is a strong biological indicator of ossification status.

BackgroundWith the appearance of oral direct-acting antivirals (DAAs), the field of hepatitis C virus (HCV) treatment has been dramatically changed. This evolution makes possible for all oral treatments to be available for the treatment of HCV-infected patients. The aims of this review were to report the efficacy and safety of sofosbuvir (SOF)-based regimens for the treatment of patients with chronic HCV infection and to provide our clinical perspectives on these regimens.MethodsA literature search of clinical studies published in PubMed and posted on ClinicalTrials.gov website was performed to identify studies evaluating the efficacy or safety of SOF-containing treatment regimens.ResultsA total of 23 clinical trials were examined in the review. The evaluated SOF-based regimens are as follows: SOF/daclatasvir (DCV) ± ribavirin (RBV), SOF/ledipasvir (LDV) ± RBV, SOF/simeprevir (SMV), SOF/velpatasvir (VEL) ± RBV, and SOF/RBV ± peginterferon (peg-IFN). These SOF-based regimens were at least effective and safe for HCV-infected patients with or without cirrhosis. The SOF/VEL ± RBV regimen, a pan-genotypic DAA regimen, was effective for the treatment of patients with HCV genotype 1, 2, 3, 4, 5, or 6 infection. The 24-week SOF/RBV regimen was as effective as the 12-week SOF/RBV/peg-IFN regimen. Patients with HCV genotype 3 infection could have benefits from the use of the 24-week SOF/RBV regimen. For cirrhotic patients with HCV genotype 3 infection, the 12-week SOF/RBV/peg-IFN regimen could be considered as an alternative treatment option when access to SOF-based regimens with other DAAs is limited. In the included studies, significant adverse events due to SOF-based regimens were not reported.ConclusionThe clinical trials suggest that SOF-based treatment regimens for HCV-infected patients with or without cirrhosis can be at least effective and safe patient-convenient medications. However, it is necessary to monitor HCV-infected patients, since rare adverse events, drug–drug interactions, and drug–disease interactions can occur in real clinical settings.

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