Aims Aberrant activation of cardiac fibroblasts leads to cardiac fibrosis, and evolving evidences suggest that endogenous bioactive substances derived from cardiac fibroblasts regulate cardiac fibroblasts activation in an autocrine/paracrine manner. Here we first presented evidence that cardiac fibroblasts can synthesize and secrete calcitonin gene-related peptide (CGRP), therefore, this study aimed to investigate the role of cardiac fibroblasts-derived CGRP in cardiac fibroblasts activation and its regulative mechanism. Methods and results The abundantly expression of CGRP in rat, mouse, and human myocardium allowed us to explore the cellular origin of CGRP, and found that the cardiac CGRP was mainly derived from cardiac fibroblasts. Activating TRPA1 with a specific agonist allyl isothiocyanate promoted the synthesis and secretion of CGRP, as well as intracellular Ca2+. These effects were reversed by TRPA1-specific antagonist HC030031 and Ca2+ chelator BAPTA-AM. TGF-β1 was applied to induce the activation of cardiac fibroblasts, and found that TGF-β1 can increase the mRNA expression and secretion levels of CGRP in cardiac fibroblasts. Either CGRP8–37 (CGRP receptor antagonist) or α-CGRP small interfering RNA (siRNA) aggravated TGF-β1-induced proliferation, differentiation, collagen production, and instigated inflammation in cardiac fibroblasts. Moreover, TGF-β1-induced NF-κB activation including IκBα phosphorylation and p65 nuclear translocation were also promoted by CGRP8–37 and α-CGRP siRNA. NF-κB inhibitor pyrrolidinedithiocarbamate ammonium (PDTC) reversed the effects of CGRP8–37 on NF-κB activation. The promotive effects of CGRP8–37 on TGF-β1-induced activation of cardiac fibroblasts were all reversed by PDTC. Monocrotaline (MCT) induces pulmonary arterial hypertension, progressively leading to right ventricular fibrosis. This model of cardiac fibrosis was developed here to test the potentially beneficial effects of TRPA1 activation in vivo. The non-toxic TRPA1 agonist Cinnamaldehyde (CA) inhibited MCT-induced elevation in right ventricle systolic pressure, RV/LV + S, and right ventricular collagen accumulation, as well as down-regulation of CGRP. CA increased the synthesis and secretion of CGRP, and inhibited TGF-β1-induced activation in cardiac fibroblasts. Conclusion Our data suggested an autocrine role for cardiac fibroblasts-derived CGRP in suppressing activation of cardiac fibroblasts through inhibiting NF-κB activation. Increasing autocrine CGRP by activating TRPA1 can ameliorate cardiac fibrosis. These findings support the notion that CGRP derived from cardiac fibroblasts is an endogenous suppressor of cardiac fibrosis.

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The aim of this study was to compare the accuracy of the Demirjian method and the Demirjian method as revised by Willems for age estimation based on orthopantomograms from central southern Chinese Han population aged 8-16 years. Discrepancies between chronological and estimated ages were statistically evaluated by analyzing 1249 orthopantomograms from 603 girls and 646 boys. Using the Demirjian method, the mean age estimates underestimated chronological age by 0.03 years (p = 0.48) for girls and overestimated it by 0.03 years (p = 0.59) for boys; these differences with respect to chronological age were not statistically significant. In contrast, the Willems method underestimated chronological age by 0.54 years (p < 0.01) for girls and 0.44 years (p < 0.01) for boys; these differences with respect to chronological age were statistically significant. Compared to the Demirjian method, the overall mean absolute error generated using the Willems method was slightly higher (0.85 and 0.86 years, respectively). Since the Demirjian method was more accurate, we highly recommend that it should be applied when estimating dental age in the Chinese Han population. Further modifications of these two methods for populations from other regions and additional studies of other age groups are warranted.

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