Association between flavonoids intake and dental caries in children and adolescents: a cross-sectional study from the NHANES database.

BACKGROUND: Worldwide, dental caries is a bacterial biofilm-mediated condition with a high morbidity in children and adolescents. Flavonoids are a class of active natural products with antibacterial and anti-inflammatory effect. In vivo and in vitro studies have shown that they can promote tooth mineralization and reduce inflammation. However, the association of flavonoids intake and dental caries in children and adolescents remain unclear. AIM: This study was to evaluated the association of flavonoid and its subclass intake and dental caries in children and adolescents. METHODS: Data of participants aged 2-17 years were extracted from the National Health and Nutrition Examination Survey (NHANES) database (2017-2018). Dental caries was measured via the decayed or filled surfaces in primary teeth or permanent teeth (dfs/DFS) index. The weighted univariable and multivariable logistic regression models were utilized to explore the association of flavonoids intake with dental caries in children and adolescents, with odds ratios (ORs) with 95% confidence intervals (CIs). Subgroups analyses based on age, and overweight/obesity were further assessed the association. Subgroup analysis were further performed to explore whether the association between subclasses of anthocyanidins and catechins with dental caries was robust stratified by age and individual with overweight/obesity. RESULTS: Among totally 1,818 children and adolescents, 786 (43.2%) had dental caries. High intake of anthocyanidins (OR=0.69, 95%CI: 0.52-0.92) and catechins (OR=0.64, 95%CI: 0.44-0.92) were associated with lower odds of dental caries. Similar results were discovered in individuals aged ≥6 years (anthocyanidins, OR=0.62, 95%CI: 0.43-0.90; catechins, OR=0.62, 95%CI: 0.40-0.96), and without overweight/obesity (anthocyanidins, OR=0.58, 95%CI: 0.37-0.90; catechins, OR=0.51, 95%CI: 0.31-0.84). Further investigation found that high intake of cyanidin, petunidin, malvidin, peonidin, (+)-Catechin, (-)-Epigallocatechin, and (-)-epicatechin were associated with lower odds of dental caries in children and adolescents. CONCLUSION: High intake of anthocyanidins and catechins were associated with lower odds of dental caries in children and adolescents and are a promising intervention to be further explored in children and adolescents.

Expression dynamics of lymphoid enhancer-binding factor 1 in terminal Schwann cells, dermal papilla, and interfollicular epidermis.

BACKGROUND: Transcription factor lymphoid enhancer-binding factor 1 (LEF1) is a downstream mediator of the Wnt/ß-catenin signaling pathway. It is expressed in dermal papilla and surrounding cells in the hair follicle, promoting cell proliferation, and differentiation. RESULTS: Here, we report that LEF1 is also expressed all through the hair cycle in the terminal Schwann cells (TSCs), a component of the lanceolate complex located at the isthmus. The timing of LEF1 appearance at the isthmus coincides with that of hair follicle innervation. LEF1 is not found at the isthmus in the aberrant hair follicles in nude mice. Instead, LEF1 in TSCs is found in the de novo hair follicles reconstituted on nude mice by stem cells chamber graft assay. Cutaneous denervation experiment demonstrates that the LEF1 expression in TSCs is independent of nerve endings. At last, LEF1 expression in the interfollicular epidermis during the early stage of skin development is significantly suppressed in transgenic mice with T-cell factor 3 (TCF3) overexpression. CONCLUSION: We reveal the expression dynamics of LEF1 in skin during development and hair cycle. LEF1 expression in TSCs indicates that the LEF1/Wnt signal might help to establish a niche at the isthmus region for the lanceolate complex, the bulge stem cells and other neighboring cells.

Spatial association of SEMA3C with nerve endings/terminal Schwann cells in hair follicle isthmus region.

Nerve endings and terminal Schwann cells (TSCs) specifically and densely surround hair follicle at isthmus area, forming a neuromuscular-junction-like structure called lanceolate complex. The interplay between neuronal components and epidermis in this specialized structure enables hair to properly sense complex stimuli from environments. However, how nerves precisely attach to and innervate this specific region during development remains to be elucidated. Here, we demonstrate that SEMA3C, a secreted protein member of semaphorin family responsible for axonal guidance, is localized right below sebaceous gland and in close approximation with nerve endings and TSCs processes all through the entire hair cycle. SEMA3C protein is deposited outside of epithelial cells and its expression is independent on the presence of nerve endings/TSCs. SEMA3C is also found in portions of dermal papilla at growth phase. The tight spatial association of SEMA3C with lanceolate complex suggests that it might play roles in establishment and/or maintenance of the lanceolate complex in hair follicle.

A qualitative transcriptional signature for the histological reclassification of lung squamous cell carcinomas and adenocarcinomas.

BACKGROUND: Targeted therapy for non-small cell lung cancer is histology dependent. However, histological classification by routine pathological assessment with hematoxylin-eosin staining and immunostaining for poorly differentiated tumors, particularly those from small biopsies, is still challenging. Additionally, the effectiveness of immunomarkers is limited by technical inconsistencies of immunostaining and lack of standardization for staining interpretation. RESULTS: Using gene expression profiles of pathologically-determined lung adenocarcinomas and squamous cell carcinomas, denoted as pADC and pSCC respectively, we developed a qualitative transcriptional signature, based on the within-sample relative gene expression orderings (REOs) of gene pairs, to distinguish ADC from SCC. The signature consists of two genes, KRT5 and AGR2, which has the stable REO pattern of KRT5 > AGR2 in pSCC and KRT5 < AGR2 in pADC. In the two test datasets with relative unambiguous NSCLC types, the apparent accuracy of the signature were 94.44 and 98.41%, respectively. In the other integrated dataset for frozen tissues, the signature reclassified 4.22% of the 805 pADC patients as SCC and 12% of the 125 pSCC patients as ADC. Similar results were observed in the clinical challenging cases, including FFPE specimens, mixed tumors, small biopsy specimens and poorly differentiated specimens. The survival analyses showed that the pADC patients reclassified as SCC had significantly shorter overall survival than the signature-confirmed pADC patients (log-rank p = 0.0123, HR = 1.89), consisting with the knowledge that SCC patients suffer poor prognoses than ADC patients. The proliferative activity, subtype-specific marker genes and consensus clustering analyses also supported the correctness of our signature. CONCLUSIONS: The non-subjective qualitative REOs signature could effectively distinguish ADC from SCC, which would be an auxiliary test for the pathological assessment of the ambiguous cases.

Chemical or genetic Pin1 inhibition exerts potent anticancer activity against hepatocellular carcinoma by blocking multiple cancer-driving pathways.

Hepatocellular carcinoma (HCC) is one of the most prevalent and malignant cancers with high inter- and intra-tumor heterogeneity. A central common signaling mechanism in cancer is proline-directed phosphorylation, which is further regulated by the unique proline isomerase Pin1. Pin1 is prevalently overexpressed in human cancers including ~70% of HCC, and promotes tumorigenesis by activating multiple cancer-driving pathways. However, it was challenging to evaluate the significance of targeting Pin1 in cancer treatment until the recent identification of all-trans retinoic acid (ATRA) as a Pin1 inhibitor. Here we systematically investigate functions of Pin1 and its inhibitor ATRA in the development and treatment of HCC. Pin1 knockdown potently inhibited HCC cell proliferation and tumor growth in mice. ATRA-induced Pin1 degradation inhibited the growth of HCC cells, although at a higher IC50 as compared with breast cancer cells, likely due to more active ATRA metabolism in liver cells. Indeed, inhibition of ATRA metabolism enhanced the sensitivity of HCC cells to ATRA. Moreover, slow-releasing ATRA potently and dose-dependently inhibited HCC growth in mice. Finally, chemical or genetic Pin1 ablation blocked multiple cancer-driving pathways simultaneously in HCC cells. Thus, targeting Pin1 offers a promising therapeutic approach to simultaneously stop multiple cancer-driving pathways in HCC.