Effects of bioflavonoid-containing mouth rinses on optical properties of tooth-coloured dental restorative materials.

This study investigated differences in colour (ΔE00) and translucency parameter (ΔTP00) of nanofilled/microhybrid composites and a glass-ionomer cement following immersion in bioflavonoid (Citrox)- or chlorhexidine-based mouth rinses. Sixty disc-shaped specimens (N = 5/group) of Filtek Supreme (3M), Gradia Anterior (GC) and Fuji IX (GC) were exposed to Citrox/0.2%CHX (Perio+0.2, Curaprox), Citrox/0.09%CHX (Perio+0.09, Curaprox), 0.2%CHX (Savacol, Colgate-Palmolive) or distilled water by 2-min agitation daily for 28 days in an orbital shaker at 200 rpm at 37 °C. Colour recordings were performed using a clinical spectrophometer to obtain CIELab coordinates. General linear model, ANOVA, Tukey test (α = 0.05) and Pearson correlation test were used to analyse data. ΔE00 ranged between 0.33 (Gradia_Savacol_T28) and 6.35 (Fuji_Savacol_T28) (p < 0.001). ΔTP00 ranged between 0.36 (Fuji_ Perio+0.2) and 1.73 (Fuji_Savacol) (p < 0.05). Savacol resulted in higher ΔE00 of Filtek and Fuji and ΔTP00 of Filtek than Perio+0.09 and Perio+0.2 (p = 0.005). Perio+0.09 and Perio+0.2 resulted in higher ΔE00 at T7 than T28 (p < 0.05). There was no correlation between ΔTP00 and ΔE00 (r = 0.445, p = 0.147). Generally, Perio+0.2 and Perio+0.09 mouth rinses produced similar or lower ΔE00 and ΔTP00 than Savacol. GIC Fuji showed higher ΔE00 and similar or higher ΔTP00 than composites Filtek and Gradia. ΔE00 in all materials decreased in Perio+0.2 and Perio+0.09 over time.

Murine obscurin and Obsl1 have functionally redundant roles in sarcolemmal integrity, sarcoplasmic reticulum organization, and muscle metabolism.

Biological roles of obscurin and its close homolog Obsl1 (obscurin-like 1) have been enigmatic. While obscurin is highly expressed in striated muscles, Obsl1 is found ubiquitously. Accordingly, obscurin mutations have been linked to myopathies, whereas mutations in Obsl1 result in 3M-growth syndrome. To further study unique and redundant functions of these closely related proteins, we generated and characterized Obsl1 knockouts. Global Obsl1 knockouts are embryonically lethal. In contrast, skeletal muscle-specific Obsl1 knockouts show a benign phenotype similar to obscurin knockouts. Only deletion of both proteins and removal of their functional redundancy revealed their roles for sarcolemmal stability and sarcoplasmic reticulum organization. To gain unbiased insights into changes to the muscle proteome, we analyzed tibialis anterior and soleus muscles by mass spectrometry, uncovering additional changes to the muscle metabolism. Our analyses suggest that all obscurin protein family members play functions for muscle membrane systems.

Novel Phosphorylations of IKKγ/NEMO.

Central to NF-κB signaling pathways is IKKγ/NEMO, a regulatory subunit of the cytoplasmic IκB kinase (IKK) complex, which undergoes various posttranslational modifications, specifically phosphorylation, to regulate its function. Furthermore, Kaposi's sarcoma-associated herpesvirus (KSHV) FADD-like interleukin-1ß (IL-1ß) converting enzyme (FLICE) inhibitory protein (vFLIP) activates the NF-κB signaling pathway by directly interacting with IKKγ/NEMO. However, the exact functions of IKKγ/NEMO phosphorylation and its KvFLIP interaction in NF-κB activation remain elusive. Here, we report two novel phosphorylation sites of IKKγ/NEMO and their negative effect on the IKKγ/NEMO-mediated NF-κB signaling pathway. First, the Src family protein tyrosine kinases (SF-PTKs), including Src, Fyn, Lyn, and Fgr, interact with and phosphorylate tyrosine residue 374 (Y374) of IKKγ/NEMO. Mutation of the Y374 residue to phenylalanine (Y374F) specifically abolished SF-PTK-mediated tyrosine phosphorylation, leading to increased tumor necrosis factor alpha (TNF-α)-induced NF-κB activity. Moreover, our mass spectrometry analysis found that the serine 377 residue (S377) of IKKγ/NEMO underwent robust phosphorylation upon KvFLIP expression. Replacement of the IKKγ/NEMO S377 residue by alanine (S377A) or glutamic acid (S377E) resulted in a significant increase or decrease of NF-κB activity and TNF-α-mediated IL-6 cytokine production, respectively. Our study thus demonstrates that the Y374 or S377 residue located at the C-terminal proline-rich domain of human IKKγ/NEMO undergoes phosphorylation upon TNF-α treatment or KvFLIP expression, respectively, resulting in the suppression of IKKγ/NEMO activity to induce NF-κB activation. This study suggests the potential phosphorylation-mediated feedback negative regulation of IKKγ/NEMO activity in the NF-κB signaling pathway. IMPORTANCE Since unchecked regulation of NF-κB has been linked to uncontrolled proliferation and cell death, the downregulation of the NF-κB signaling pathway is as important as its activation. Specifically, the phosphorylation-mediated modification of IKKγ/NEMO is a critical regulatory mechanism of NF-κB activity. Here, we report two novel phosphorylations of IKKγ/NEMO and their negative effects on the NF-κB signaling pathway. First, the Src family protein tyrosine kinase interacts with and phosphorylates tyrosine residue 374 of IKKγ/NEMO, suppressing tumor necrosis factor alpha (TNF-α)-induced NF-κB activity. Additionally, Kaposi's sarcoma-associated herpesvirus (KSHV) FADD-like interleukin-1ß (IL-1ß) converting enzyme (FLICE) inhibitory protein (KvFLIP) expression induces a robust phosphorylation of the serine 377 residue of IKKγ/NEMO, resulting in a significant decrease of NF-κB activity. Our study thus demonstrates that the Y374 or S377 residue of IKKγ/NEMO undergoes phosphorylation upon TNF-α treatment or KvFLIP expression, respectively, resulting in the suppression of IKKγ/NEMO activity to induce NF-κB activation. This also suggests the potential phosphorylation-mediated feedback negative regulation of IKKγ/NEMO activity in the NF-κB signaling pathway.