The cellular and molecular pathways of fluoride toxicity in osteoblasts are not very well understood. Therefore, the objective of the present study was to evaluate the effects of sodium fluoride (NaF) on caprine osteoblasts cultured in vitro. Caprine osteoblasts at 2.0 x 10(-4) cells/ml were incubated in vitro with NaF at 0, 10(-8), 10(-7), 10(-6), 10(-5), 10(-4), 5.0 x 10(-4), and 10(-3) M, and then proliferation, differentiation, apoptosis, calcification, and alkaline phosphatase activity were examined. Also, the effect of NaF on osteoblastic cell viability and the molecular events leading to apoptosis were determined. Electron microscopy revealed cytoplasmic and nuclear alterations in the ultrastructure of osteoblasts exposed to various NaF concentrations. A cell-based quantitative evaluation of the MTT assay showed that NaF at concentrations of 10(-8) to 10(-5) M promoted cell proliferation, whereas at 10(-4) to 10(-3) M it suppressed cell proliferation and induced apoptosis. Alkaline phosphatase (ALP) activity and mineralization ability increased in cells treated at 10(-8) to 10(-5) M with sodium versus the controls, but decreased at 5.0 x 10(-4) to 10(-3) M dosage. The highest incidence of early apoptotic cells and late apoptotic cells was reached (3.33% and 2.92%, respectively) under NaF concentration of 10(-4) M. In conclusion, results of this study indicated that NaF modulates osteoblast proliferation and differentiation in a dose-dependent manner and modified osteoblast metabolism bidirectionally, suggesting NaF may play a significant role in osteoblast physiology.

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Follicular development plays a key role in poultry reproduction, affecting clutch traits and thus egg production. Follicular growth is determined by granulosa cells (GCs), theca cells (TCs), and oocyte at the transcription, translation, and secretion levels. With the development of bioinformatic and experimental techniques, non-coding RNAs have been shown to participate in many life events. In this study, we investigated the transcriptomes of GCs and TCs in three different physiological stages: small yellow follicle (SYF), smallest hierarchical follicle (F6), and largest hierarchical follicle (F1) stages. A differential expression (DE) analysis, weighted gene co-expression network analysis (WGCNA), and bioinformatic analyses were performed. A total of 18,016 novel circular RNAs (circRNAs) were detected in GCs and TCs, 8127 of which were abundantly expressed in both cell types. and more circRNAs were differentially expressed between GCs and TCs than mRNAs. Enrichment analysis showed that the DE transcripts were mainly involved in cell growth, proliferation, differentiation, and apoptosis. In the WGCNA analysis, we identified six specific modules that were related to the different cell types in different stages of development. A series of central hub genes, including MAPK1, CITED4, SOD2, STC1, MOS, GDF9, MDH1, CAPN2, and novel_circ0004730, were incorporated into a Cytoscape network. Notably, using both DE analysis and WGCNA, ESR1 was identified as a key gene during follicular development. Our results provide valuable information on the circRNAs involved in follicle development and identify potential genes for further research to determine their roles in the regulation of different biological processes during follicle growth.

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Purpose A liposome-coated arsenic–manganese complex, denoted as LP@MnAs x was constructed for the targeted delivery of arsenic trioxide (ATO) against carcinoma. Methods Arsenite, the prodrug of ATO, was encapsulated within a liposome via electrostatic interaction with the manganese ions. The as-prepared material was characterized with dynamic light scattering and transmission electron microscopy. The entrapment efficiency and drug loading of arsenic in the carrier were measured using inductively coupled plasma spectrometry. The in vitro release of arsenic was evaluated by using the dialysis bag method. Furthermore, the Fenton-like activity and in vitro cytodynamics research of LP@MnAs x were monitored in this work. And the cellular uptake study was used to investigate the in vitro entry mechanism. Furthermore, the cytotoxicity, cell apoptosis and cell cycle study were performed to evaluate the tumor-killing efficiency. Also, the pharmacokinetic and antitumor studies were investigated in HepG2 tumor-bearing nude mice. Results The as-prepared LP@MnAs x possessed a spherical morphology, uniformly distributed hydrodynamic diameter, and excellent drug-loading efficiency. LP@MnAs x displayed robust stability and sustained-release profile under physiological environments. LP@MnAs x could degrade with high sensitivity to the pH variation in the tumor microenvironment. As such, this could lead to a burst release profile of Mn 2+ and arsenite to achieve a synergistic therapy of chemodynamic therapy and chemotherapy. When compared to the carrier-free arsenate, in vitro experiments revealed that LP@MnAs x exhibited enhanced cellular uptake and tumor-killing efficiency. LP@MnAs x also demonstrated significantly enhanced tumor-specific in vivo distribution of arsenic, prolonged systemic circulation lifetime, and increased accumulation at the tumor site. Conclusion Based on the experimental results, LP@MnAs x is an ideal arsenic-based nanodelivery system, whereby it can improve the non-specific distribution of NaAsO 2 in vivo. Thus, this work can expand the research and application of arsenic trioxide against solid tumors.