Maternal oral exposure to low-dose BPA accelerates the onset of puberty by promoting prepubertal Kiss1 expression in the AVPV nucleus of female offspring.

As the incidence of precocious puberty has risen in recent years and the age at puberty onset is younger, children may be at increased risk for health consequences associated with the early onset of puberty. Bisphenol A (BPA) is recognized as an endocrine disruptor chemical that is reported to induce precocious puberty. The effect of BPA exposure modes, times, and doses (especially low dose) were controversial. In the present study, we evaluated the potential effects of maternal exposure to low-dose BPA on the hypothalamus, particularly on the arcuate (ARC) nucleus and anteroventral periventricular (AVPV) nucleus during peri-puberty in offspring of BPA-treated rats. Pregnant rats were exposed to corn oil vehicle, 0.05 mg·kg-1·day-1 BPA, or 5 mg·kg-1·day-1 from gestation day 1 (GD1) to postnatal day 21 (PND21) by daily gavage. Body weight (BW), vaginal opening (VO), ovarian follicular luteinization, and relevant hormone concentrations were measured; hypothalamic Kiss1 and GnRH1 levels by western immunoblot analysis were also assessed as indices of puberty onset. During or after exposure, low-dose BPA restricted BW after birth (at PND1 and PND5), and subsequently accelerated puberty onset by promoting the expression of prepubertal Kiss1 and GnRH1 in the AVPV nucleus on PND30, leading to advanced VO, an elevation in LH and FSH concentrations (on PND30). We also noted increased BW on PND30 and PND35. Maternal oral exposure to low-dose BPA altered the BW curve during the neonatal and peripubertal periods, and subsequently accelerated puberty onset by promoting prepubertal Kiss1 expression in the AVPV nucleus.

Molecular characterization of physis tissue and hormonal profiles of female rats neonatally exposed to low-dose bisphenol A.

Physis is a complex cartilaginous structure that is critical for longitudinal bone growth. As one of the endocrine-disrupting chemicals, bisphenol A (BPA) can interfere with the physis by deranging the complex networks of nutritional, cellular, paracrine, and endocrine factors, and this affects longitudinal bone growth, leading to different growth outcomes. However, the exact mechanisms underlying these phenomena remain unclear. Therefore, understanding the molecular pathways involved in the physis after neonatal exposure to low-dose BPA may permit the identification of research targets for therapeutics, which may aid in modulating the process of growth plate closure. In the present study, female Sprague-Dawley rats were exposed to 0.05 mg·kg-1·day-1 of BPA and corn oil vehicle from postnatal day 1 (PND1) to 15 via subcutaneous injection. Next-generation RNA sequencing was performed for the mRNA isolated from the physis. The levels of osteocalcin (OC), growth hormone (GH), and insulin-like growth factor 1 (IGF-1) were measured on PND30 (BPA0.05mg vs. Vehicle; n = 5 for each group). We observed statistically significant enrichment of gene sets in the BPA0.05mg tissues compared with the Vehicle tissues. Further analysis of the differentially expressed genes (DEGs) identified BPA0.05mg-specific networks of secreted proteins (LEP, NPY, AGT, ACE2, C4B, and C4BPA) as well as those of local matrix and protease proteins (FBN2, LAMC2, ADAMTS16, and ADAMTS19). Furthermore, the levels of OC and GH were affected by BPA exposure. Our results revealed the specific molecular characteristics of physis contaminated with BPA and may provide new clues for physis maturation and supervision of industrial products and occupational exposure.

Cinnamaldehyde protects against ligature-induced periodontitis through the inhibition of microbial accumulation and inflammatory responses of host immune cells.

Cinnamaldehyde (CA), the main active ingredient in cinnamon, has been proved to be a potential candidate for controlling inflammation; however, there has been little evidence demonstrating its role in alleviating periodontitis. The aim of this study was to investigate the effect of orally administered CA on ligature-induced periodontitis in mice and the administration of CA on the Porphyromonas gingivalis (Pg) supernatant-induced inflammatory responses of murine macrophages and human periodontal ligament cells (HPDLCs). In vivo experiments showed that the oral administration of CA significantly inhibited bone resorption, the accumulation of anaerobic bacteria and host immuno-inflammatory responses in ligature-induced periodontitis in mice. In vitro, CA inhibited the expression of Pg supernatant-induced IL6, IL8, TNFA and IL1B and reactive oxygen species in RAW 264.7 and HPDLCs, involving the inactivation of the NFKB signaling pathway, which was activated by the Pg supernatant. Also, the expression of adherent and chemotactic-related cytokines was inhibited by CA, accompanied with a reduction in adherent HPDLCs. Moreover, CA ameliorated the cellular senescence of HPDLCs induced by H2O2, together with a decrease in senescence-associated-ß-galactosidase positive cells and decrease in the expression of P53, P21 and P16. Furthermore, CA promoted the osteogenic differentiation of HPDLCs with an increase in alkaline phosphatase expression and activity, formation of more mineralization nodules, and increased the expression of bone sialoprotein and osteopontin. Conclusions: Daily diet-added CA may be beneficial for oral health care, especially for the control of periodontic disease by suppressing the dysbiosis of biofilms and inhibiting the immunoinflammatory responses of migrated macrophages and local resident periodontal ligament cells to specific pathogen irritations.

Novel fabrication and biological characterizations of AgNPs-decorated PEEK with gelatin functional nanocomposite to improve superior biomedical applications.

There is an increasing interest in the use of polyether ether ketone (PEEK) for biomedical applications. Herein, we have developed silver nanoparticles (AgNPs) decorated PEEK with gelatin (GEL) nanocomposite hydrogel with enhanced antibacterial and biocompatibility through the blending method. The prepared highly porous PEEK/GEL/AgNPs nanocomposite hydrogel was characterized using SEM, TEM, FTIR, and XRD analysis. The SEM image showed that AgNPs were encapsulated in the porous PEEK/GEL hydrogel; within this porous hydrogel, the AgNPs were homogeneously dispersed. Furthermore, the tensile strength, flexural strength, and Young's modulus were 99 ± 2.4 MPa, 154 ± 7.7 MPa, and 2.3 ± 0.1 GPa, respectively, when AgNPs were added to PEEK/GEL hydrogels it exhibited the mechanical performances. The antibacterial assays demonstrate that the AgNPs-decorated PEEK/GEL nanocomposite hydrogel effectively inhibits the antibacterial effect against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria, respectively. Then, MC3T3-E1 cells demonstrated that the AgNPs-decorated PEEK/GEL nanocomposite hydrogel significantly enhanced cell viability and superior alkaline phosphatase (ALP) activity compared with PEEK/GEL hydrogel. This work opens a new avenue of the facile and effective modification of PEEK/GEL/AgNPs nanocomposite hydrogel has increased in vitro antibacterial and biocompatibility properties has great potential to be used as biomedical applications.

Levels of SERPIN family proteins in peri-implant crevicular fluid in patients with peri-implantitis.

PURPOSE: Serine protease inhibitors (SERPINs) family has been discovered in many disorders with proteolysis mechanisms. Our study determined the SERPINBs protein expression via public-based GEO databases and further validated by peri-implant crevicular fluid (PICF) of peri-implantitis patients and healthy recruiters. METHODS: This study is a retrospective analysis. A total of 123 participants of Fujian Medical University Fujian Stomatological Hospital, consisting of 58 cases of peri-implantitis and 65 samples of healthy control were retrospectively analyzed by ELISA assays and explored the gene enrichment pathways and clinical significance of SERPINBs expression accompanied by two different cytokines (IL-6 and TNF-α). Moreover, the clinical significance of SERPINBs was evaluated in peri-implantitis patients with PICF samples by the receiver operating curve (ROC) using the area under the curve (AUC). RESULTS: KEGG database showed that Starch and sucrose metabolism, Retrograde endocannabinoid signaling, Prion diseases, Pentose phosphate pathways, and Olfactory pathways are up-regulated; GO database showed that synapse organization, synapse assembly, sequestering of triglyceride, sensory perception of smell, and regulation of synapse organization pathways are up-regulated. SERPINBs were overexpressed in peri-implant tissues and peri-implantitis patients with PICF. SERPINBs was positively correlated to IL-6 and TNF-α in peri-implantitis patients with PICF. The ROC-AUCs of SERPINBs achieved a significantly higher range from 0.895 to 0.939 in peri-implantitis patients with PICF. Therefore, certain SERPINBs expressions were not only perceived through PICF and peri-implant tissues but also showed potential significance in peri-implantitis. CONCLUSION: SERPINBs play an influential role in the pathogenesis of peri-implantitis via binding with other inflammatory cytokines.