Atf7ip Inhibits Osteoblast Differentiation via Negative Regulation of the Sp7 Transcription Factor.

Epigenetic modifications are critical for cell differentiation and growth. As a regulator of H3K9 methylation, Setdb1 is implicated in osteoblast proliferation and differentiation. The activity and nucleus localization of Setdb1 are regulated by its binding partner, Atf7ip. However, whether Atf7ip is involved in the regulation of osteoblast differentiation remains largely unclear. In the present study, we found that Atf7ip expression was upregulated during the osteogenesis of primary bone marrow stromal cells and MC3T3-E1 cells, and was induced in PTH-treated cells. The overexpression of Atf7ip impaired osteoblast differentiation in MC3T3-E1 cells regardless of PTH treatment, as measured by the expression of osteoblast differentiation markers, Alp-positive cells, Alp activity, and calcium deposition. Conversely, the depletion of Atf7ip in MC3T3-E1 cells promoted osteoblast differentiation. Compared with the control mice, animals with Atf7ip deletion in the osteoblasts (Oc-Cre;Atf7ipf/f) showed more bone formation and a significant increase in the bone trabeculae microarchitecture, as reflected by µ-CT and bone histomorphometry. Mechanistically, Atf7ip contributed to the nucleus localization of Setdb1 in MC3T3-E1, but did not affect Setdb1 expression. Atf7ip negatively regulated Sp7 expression, and through specific siRNA, Sp7 knockdown attenuated the enhancing role of Atf7ip deletion in osteoblast differentiation. Through these data, we identified Atf7ip as a novel negative regulator of osteogenesis, possibly via its epigenetic regulation of Sp7 expression, and demonstrated that Atf7ip inhibition is a potential therapeutic measure for enhancing bone formation.

[Animal Experimental Study of the Role of Menthol and Cineole, Two Tobacco Additives, on Nicotine Dependence].

OBJECTIVE: To establish a nicotine intravenous self-administration rat model, and to examine, with this model, the effects of two flavoring additives, menthol and cineole, on nicotine dependence. METHODS: Thirty male Sprague-Dawley (SD) rats were included in the study. After jugular venous catheterization was performed, fixed concentration of nicotine was administered in order to train the rats and establish the rat model of intravenous self-administration groups, receiving intraperitoneal injection of menthol, cineole, and dimethyl sulfoxide (DMSO), the vehicle that was used for the control group. The rats were tested with different fixed-ratio (FR) schedules, including FR1 schedule, in which the rat received one nicotine infusion for every active nose poke, FR2 schedule, in which the rat received one nicotine infusion for every two active nose pokes, and FR5 schedule, in which the rat received one nicotine infusion for every five active nose pokes. The number of active and inactive poke responses and the number of nicotine infusion were documented accordingly. RESULTS: After 10 days of training in nicotine self-administration, the 30 rats demonstrated significant increase in the number of active poke responses and the number of nicotine infusion, which were maintained at a stable and relatively high level. The number of active poke responses was significantly higher that of inactive poke responses ( P< 0.001). The rat model of intravenous nicotine self-administration was successfully established. In the testing phase, under the FR2 schedule, the menthol group showed a reduced number of active poke responses ( P=0.020). Under the FR5 schedule, the groups showed obvious interaction between time and the number of active poke responses ( P<0.011), with the menthol group showing reduced number of active poke responses on day three ( P=0.011) and the cineole group showing rising number of active poke responses on day three ( P=0.003). The DMSO control group did not show any significant change. CONCLUSIONS: Menthol and cineole are shown to have an effect on nicotine dependence. When there is relative difficulty involved in obtaining nicotine, menthol suppresses nicotine dependence, whereas cineole enhances nicotine dependence.

The Properties of HPMC:PEO Extended Release Hydrophilic Matrices and their Response to Ionic Environments.

PURPOSE: Investigate the extended release behaviour of compacts containing mixtures of hydrophilic HPMC and PEO in hydrating media of differing ionic strengths. METHODS: The extended release behaviour of various HPMC:PEO compacts was investigated using dissolution testing, confocal microscopy and magnetic resonance imaging, with respect to polymer ratio and ionic strength of the hydrating media. RESULTS: Increasing HPMC content gave longer extended release times, but a greater sensitivity to high ionic dissolution environments. Increasing PEO content reduced this sensitivity. The addition of PEO to a predominantly HPMC matrix reduced release rate sensitivity to high ionic environments. Confocal microscopy of early gel layer development showed the two polymers appeared to contribute independently to gel layer structure whilst together forming a coherent and effective diffusion barrier. There was some evidence that poorly swollen HPMC particles added a tortuosity barrier to the gel layer in high ionic strength environments, resulting in prolonged extended release. MRI provides unique, non-invasive spatially resolved information from within the HPMC:PEO compacts that furthers our understanding of USP 1 and USP 4 dissolution data. CONCLUSIONS: Confocal microscopy and MRI data show that combinations of HPMC and PEO have advantageous extended release properties, in comparison with matrices containing a single polymer.

Using the concept of preperitoneal membrane anatomy in total extraperitoneal prosthesis: a preliminary report.

Purpose: Total extraperitoneal prosthesis (TEP) is one of the most commonly used laparoscopic inguinal hernia repair procedures. This work aims to report the application of membrane anatomy to TEP and its value in intraoperative space expansion. Methods: The clinical data of 105 patients, from January 2018 to May 2020, with inguinal hernia who were treated with TEP (58 patients in the General Department of the Second Hospital of Sanming City, Fujian Province, and 47 patients in the General Department of the Zhongshan Hospital Affiliated to Xiamen University) were retrospectively analyzed. Results: All surgeries were successfully completed under the guidance of the concept of preperitoneal membrane anatomy. The operation time was 27.5 ± 9.0 min, blood loss was 5.2 ± 0.8 ml, and the peritoneum was damaged in six cases. The postoperative hospital stay was 1.5 ± 0.6 days, and five cases of postoperative seroma occurred, all self-absorbed. During the follow-up period of 7-59 months, there was no case of chronic pain and recurrence. Conclusion: The membrane anatomy at the correct level is the premise of a bloodless operation to expand the space while protecting adjacent tissues and organs to avoid complications.

Polyurethane-based bionic material simulating the Vis-NIR spectrum and thermal infrared properties of vegetation.

Poor stability, the toxicity of the used colorants and complex structure are the main problems for the current spectral simulation materials for vegetation. In this paper, a lightweight (0.052 g cm-3) and environmentally friendly bionic porous spectrum simulation material (BPSSM) was developed to simulate the Vis-NIR spectra of natural leaves. The porous structure of BPSSM was used to simulate the mesophyll tissue, which endows the BPSSM with a near-infrared plateau. Moreover, the relationship between pore structure (size, open porosity and volume density) and near-infrared plateau in the spectrum was also studied. The chlorophyll of leaves was simulated by vat dyes or organic pigments, and the green apex and red edge characteristics in the visible region were further adjusted by the chlorophyllin sodium copper salt. The water absorption of BPSSM with 100-120% water contents are consistent with the natural leaves spectral curve channel. Finally, the spectral correlation coefficients (r m) between BPSSM and different natural leaves are up to 0.984, suggesting that the BPSSM is universally applicable for the simulation of different leaves. Interestingly, the average radiant temperature difference between BPSSM and natural leaves is 0.25 °C within 24 hours, indicating it has similar thermal infrared properties to natural leaves. Moreover, the BPSSM can be combined with textiles to obtain a composite fabric, and its breaking strength and photostability were explored.

Discovery of (E)-3-((styrylsulfonyl)methyl)pyridine and (E)-2-((styrylsulfonyl)methyl)pyridine derivatives as anticancer agents: synthesis, structure-activity relationships, and biological activities.

ON01910.Na is a highly effective anticancer agent that induces mitotic arrest and apoptosis. Clinical studies with ON01910 in cancer patients have shown efficacy along with an impressive safety profile. While ON01910 is highly active against cancer cells, it has a low oral availability and requires continuous intravenous infusion or multiple gram doses to ensure sufficient drug exposure for biological activity in patients. We have identified two novel series of styrylsulfonyl-methylpyridines. Lead compounds 8, 9a, 18 and 19a are highly potent mitotic inhibitors and selectively cytotoxic to cancer cells. Impressively, these compounds possess excellent pharmaceutical properties and two lead drug candidates 9a and 18 demonstrated antitumor activities in animal models.