Expression of TGF and Shh Signaling Molecules after TGF-β or Shh Inhibition.

<p>(A) TGF-β signaling inhibitor, ALK5 kinase inhibitor, mitigated CsA-upregulated mRNA expression of Shh, Gli, and TGF-β by RT-PCR and protein expression Shh and TGF-β by Western blotting. (B) Shh signaling inhibitor, cyclopamine, did not alter CsA-upregulated TGF-β expression, but it did attenuate CsA-upregulated Shh expression. Experiments were repeated 3 times. Data are expressed as mean and SD by one-way ANOVA; a–c, subsets obtained after <i>post hoc</i> analysis.</p

Role of Shh in HGF Proliferation after CsA Treatment.

<p>(A) Shh mRNA and protein levels were upregulated in HGFs after CsA treatment (1000 ng/mL) at 48 h and 72 h, respectively. (B) Shh enhanced cell proliferation and (C) inhibition of Shh attenuated CsA-enhanced cell proliferation (C). HT-29, SW480, and MCF-7 cell lines served as positive controls. Experiments were repeated 3 times. Data are expressed as mean and SD; *significantly different from the control group at <i>p</i><0.05 by Student’s <i>t</i>-test or one-way ANOVA; a–c, subsets obtained after <i>post hoc</i> analysis.</p

Model of Crosstalk between Shh and TGF-β Signaling in CsA-Enhanced Cell Proliferation.

<p>CsA-enhanced cell proliferation in HGFs <i>via</i> Shh signaling is modulated by TGF-β. The schematic diagram is generated, according to our findings from this study. CsA may upregulate the Shh expression directly or indirectly <i>via</i> TGF-β signaling. Increased Shh expression leads to Gli activation and contributes to HGF proliferation. TGF-β RI kinase inhibitor V and cyclopamine inhibit the TGF-β and Shh pathways, respectively.</p

Role of TGF-β in HGF Proliferation after CsA Treatment.

<p>(A) CsA enhanced cell proliferation by MTS assay and RT-PCR analysis of PCNA. (B) CsA increased TGF-β mRNA and protein expressions, examined by RT-PCR (24 h) and Western blotting (48 h). (C) TGF-β enhanced cell proliferation and (D) inhibition of TGF-β mitigated the CsA-enhanced cell proliferation. Experiments were repeated 3 times. Data are expressed as mean and SD; *significantly different from the control group at <i>p</i><0.05 by Student’s <i>t</i>-test or one-way ANOVA; and a–b, subsets obtained after <i>post hoc</i> analysis.).</p

Supplementary materials-Table-R1-clean.docx

   Type 2 diabetes mellitus and periodontitis: Bi-directional association in population-based 15-year retrospective cohorts</p

Incidence and hazard ratios of PD for amalgam filling patients compared with non-amalgam filling patients by demographic characteristics and comorbidities.

<p>Incidence and hazard ratios of PD for amalgam filling patients compared with non-amalgam filling patients by demographic characteristics and comorbidities.</p

Amalgam filling cohort and non-amalgam filling cohort selection flowchart.

<p>Amalgam filling cohort and non-amalgam filling cohort selection flowchart.</p

Kaplan-Meier model for estimating the PD-free survival probability of amalgam filling and non-amalgam filling patients.

<p>Kaplan-Meier model for estimating the PD-free survival probability of amalgam filling and non-amalgam filling patients.</p

Previous published works comparing the outcomes, particularly the incidence rate of PD between amalgam filling patients (AF) and non-amalgam filling patients (non-AF).

<p>Previous published works comparing the outcomes, particularly the incidence rate of PD between amalgam filling patients (AF) and non-amalgam filling patients (non-AF).</p

Univariate and multivariable hazard ratios of covariates for all-cause PD among amalgam filling patients.

<p>Univariate and multivariable hazard ratios of covariates for all-cause PD among amalgam filling patients.</p