[Evaluation of the effect of cattle calcined bone grafting material to repair alveolar bone defect after tooth extraction].

PURPOSE: To verify the efficacy and safety of calcined cattle bone grafting material in filling alveolar bone defect after tooth extraction. METHODS: A randomized, bind, parallel, positive-control multicenter clinical trial was conducted. A total of 280 subjects were randomly assigned to either the experimental group (calcined cattle bone group) or control group (Bio-Oss group) equally. The main efficacy indicator was the imaging changes 24 weeks after material implantation. Secondary efficacy indicators were wound healing, rejection, bone metabolism, post-filling symptoms and signs of bone infection. The safety of material was assessed by the incidence of adverse events and serious adverse events. SAS 8.2 software package was used for statistical analysis. RESULTS: A total of 280 cases were included, of them 267 cases completed the study while 13 cases fell off. The effective rate of FAS(PPS) was 90.58%(97.46%) in the experimental group and 87.05% (95.04%) in the control group. The difference of effective rate between the experimental group and control group (95%CI) was 3.53% (-3.88%, 10.94%) of FAS, 2.42% (-2.38%, 7.22%) of PPS, and there was no significant difference between the two groups. The incision healing of the two groups was good, and the incidence of rejection, bone infection signs, post-filling symptoms and bone metabolic changes was very low. The incidence of adverse events was similar in the two groups, and no serious adverse events related to the study materials occurred. CONCLUSIONS: The efficacy of calcined cattle bone grafting material in filling alveolar bone defect after tooth extraction is not inferior to that of Bio-Oss, and it is safe and effective for alveolar bone defect repair.

Chronic minocycline treatment exerts antidepressant effect, inhibits neuroinflammation, and modulates gut microbiota in mice.

RATIONAL: Minocycline is a second-generation, semi-synthetic tetracycline, and has broad spectrum-antibacterial activity. Interestingly, many studies have demonstrated that minocycline is beneficial for depression, which may be due to its effects on neuroinflammation modulation. Recently, gut microbiota imbalance has been found in depression patient and animal models. OBJECTIVES: Based on the fact of minocycline usually acting as an antibiotic and the relationship between depression, gut microbiota, and neuroinflammation, we designed this study to detect the effects of chronic minocycline treatment on antidepression, neuroinflammation, and gut microbiota modulation. RESULTS: Our results showed that minocycline treatment for 4 weeks, not acute treatment, exerted antidepressant effect in mice exposed to unpredictable chronic mild stress (CUMS). Further results suggested that chronic minocycline treatment inhibited neuroinflammation of hippocampus and altered species abundance and metabolites of gut microbiota. Meantime, we found that chronic minocycline treatment ameliorated intestinal barrier disruption and reduced the bacteriological indexes, such as diamine oxidase, C-reaction protein, and endotoxin in peripheral blood of CUMS mice. CONCLUSIONS: To sum up, our findings confirm that chronic minocycline treatment exerts the antidepressant effect, inhibits neuroinflammation, and modulates gut microbiota. All of these imply that the antidepressant mechanism of chronic minocycline treatment is maybe due to the combined action of neuroinflammation and gut microbiota modulation, which need further prospective studies.

Chronic minocycline treatment reduces the anxiety-like behaviors induced by repeated restraint stress through modulating neuroinflammation.

Anxiety disorders are chronic, disabling conditions across the world, and bring a great burden to individuals and society. Although advances have been made in understanding of the pathophysiology of these diseases, no mechanistically new drugs for anxiety disorders have reached the market in the past two decades. Some evidence indicates that stress increases neuroinflammatory signaling, which is related to the development of anxiety and depression. Minocycline, a broad-spectrum tetracycline-antibiotic, has been reported to suppress microglia activation-mediated brain endogenous inflammation. However, it is still unknown whether minocycline can be developed to treat stress-induced anxiety disorders and what is the underlying mechanisms. We chose the anxiety model induced by repeated stress consisting of 2 h of restraint on each of 7 consecutive days. The behavioral test results showed that chronic minocycline treatment, not acute minocycline treatment, increased the time spent in the center area in the open field test and the number of open arm entries and time spent in open arms in the elevated plus maze test, which were comparable with the effect of buspirone. Further mechanism studies demonstrated that chronic minocycline treatment inhibited the microglia activation and decreased the levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α). In addition, peroxisome proliferator-activated receptor gamma/ nuclear factor kappa B (PPAR-γ/NF-κB) signaling pathway was also modulated by chronic minocycline treatment. In conclusion, our findings support the hypothesis that immune dysregulation plays an important role in stress-induced anxiety disorders, and minocycline can be developed to be used in these diseases.

The octanol/water distribution coefficients of ardipusilloside-I and its metabolites, and their permeation characteristics across Caco-2 cell monolayer.

BACKGROUND: Ardipusilloside-I (ADS-I) is a triterpenoid saponin extracted from Chinese medicinal herb Ardisiapusill A. DC. Previous studies have demonstrated the potent anti-tumor activities of ADS-I both in vitro and in vivo, and its main metabolites (M1 and M2) from human intestinal bacteria. However, the physicochemical properties and intestinal permeation rate of ADS-I and its metabolites are not understood. In this study, the octanol/water distribution coefficients (logP) of ADS-I and metabolites were investigated using standard shake flask technique, and their permeability properties was investigated across Caco-2 cells monolayer. RESULTS: The logP of ADS-I, M1 and M2 was -0.01, 0.95 ± 0.04, 1.57 ± 0.11, respectively. The Papp values of ADS-I, M1 and M2 (in 10 µmol/L) across Caco-2 cell monolayers from the apical (AP) to basolateral (BL) direction were 1.88 ± 0.21 × 10(-6) cm·s(-1), 4.30 ± 0.43 × 10(-6) cm·s(-1), 4.74 ± 0.47 × 10(-6) cm·s(-1), respectively. CONCLUSION: Our data indicated that ADS-I has the poorer intestinal absorption than its metabolites (M1 and M2) in these experimental systems, suggesting that the metabolites of ADS-I may be the predominant products absorbed by the intestine when ADS-I is administered orally.

Efficacy of local delivery of ardipusilloside I using biodegradable implants against cerebral tumor growth.

Ardipusilloside I (ADS-I) is a natural compound that can be isolated from the Chinese medicinal herb Ardisiapusilla A.DC, and has been reported to inhibit the growth of glioblastoma cells in cultures. This study was designed to test its efficacy by the delivery using biodegradable implants against glioblastoma in vivo. ADS-I was incorporated into polymer microspheres, which were prepared by a mixture of poly (D, L-lactic acid) and poly (D, L-lactic-co-glycolic acid) polymers and then fabricated into wafers. The anti-glioma activities of ADS-I-loaded wafers were examined by methylthiazol tetrazolium (MTT) assay in cultured rat C6 glioma cells, and by magnetic resonance imaging (MRI) and survival monitoring in C6 glioma-bearing rats. Here, we showed that ADS-I-loaded wafers sustained ADS-I release in vitro for 36 days in Higuchi model of kinetics, and had the same cytotoxic activity as ADS-I in the solution against the growth of C6 glioma cells in cultures. In C6 glioma-bearing rats, ADS-I wafer implants inhibited tumor growth in a dose-dependent matter, and were more effective than the same dosage of ADS-I in the solution. The tumor suppression efficacies of ADS-I wafer implants were positively correlated with an increase in tumor cell apoptosis and prolonged animal survival, and were associated with a decrease in vascular endothelial growth factor, C-reactive protein, tumor necrosis factor-α and interleukin-6, and an increase in interleukin-2 expression. In conclusion, this study demonstrates significant efficacy of local delivery of ADS-I using polymer implants against glioma tumor growth in vivo, suggesting the potential of ADS-I-loaded wafers for glioma treatment.