Distinct mechanisms of iron and zinc metal ions on osteo-immunomodulation of silicocarnotite bioceramics.

The immunomodulatory of implants have drawn more and more attention these years. However, the immunomodulatory of different elements on the same biomaterials have been rarely investigated. In this work, two widely used biosafety elements, iron and zinc added silicocarnotite (Ca5(PO4)2SiO4, CPS) were applied to explore the routine of elements on immune response. The immune reactions over time of Fe-CPS and Zn-CPS were explored at genetic level and protein level, and the effects of their immune microenvironment with different time points on osteogenesis were also investigated in depth. The results confirmed that both Fe-CPS and Zn-CPS had favorable ability to secret anti-inflammatory cytokines. The immune microenvironment of Fe-CPS and Zn-CPS also could accelerate osteogenesis and osteogenic differentiation in vitro and in vivo. In terms of mechanism, RNA-seq analysis and Western-blot experiment revealed that PI3K-Akt signaling pathway and JAK-STAT signaling pathways were activated of Fe-CPS to promote macrophage polarization from M1 to M2, and its immune microenvironment induced osteogenic differentiation through the activation of Hippo signaling pathway. In comparison, Zn-CPS inhibited polarization of M1 macrophage via the up-regulation of Rap1 signaling pathway and complement and coagulation cascade pathway, while its osteogenic differentiation related pathway of immune environment was NF-κB signaling pathway.

Bactericidal Mechanisms of Chlorine Dioxide against Beta-Hemolytic Streptococcus CMCC 32210.

Chlorine dioxide is a globally recognized green and efficient disinfectant. This study aims to investigate the bactericidal mechanism of chlorine dioxide using beta-hemolytic Streptococcus (BHS) CMCC 32210 as a representative strain. BHS was exposed to chlorine dioxide, the minimum bactericidal concentration (MBC) values of chlorine dioxide against BHS were determined by the checkerboard method in preparation for subsequent tests. Cell morphology was observed using electron microscopy. Protein content leakage, adenosine triphosphatase (ATPase) activity, and lipid peroxidation were determined by kits, and DNA damage was determined using agar gel electrophoresis. The concentration of chlorine dioxide during disinfection showed a linear relationship with the concentration of BHS. Scanning electron microscopy (SEM) results showed that chlorine dioxide caused significant damage to the cell walls of BHS at a concentration of 50 mg/L, but had no significant effect on Streptococcus exposed to different exposure times. Furthermore, the extracellular protein concentration increased with increasing chlorine dioxide concentration, while the total protein content remained unchanged. The activities of Na+/K+-ATPase and Ca2+/Mg2+-ATPase decreased with increasing chlorine dioxide concentration. Chlorine dioxide treatment led to significant lipid peroxidation and DNA degradation in BHS. Leakage of intracellular components indicated that chlorine dioxide damaged the cell membrane of BHS. Chlorine dioxide exposure resulted in oxidative damage to lipids and proteins, which negatively impacted the cell wall and membrane of Streptococcus. This caused increased permeability and inactivation of key enzymes (Na+/K+-ATPase and Ca2+/Mg2+-ATPase) involved in respiratory metabolism, ultimately leading to DNA degradation and bacterial death due to either content leakage or metabolic failure.

Latent TGF-beta binding protein-1 plays an important role in craniofacial development

Abstract Objective: This study aims to replicate the phenotype of Ltbp1 knockout mice in zebrafish, and to address the function of LTBP1 in craniofacial development. Methods: Whole mount in situ hybridization (WISH) of ltbp1 was performed at critical periods of zebrafish craniofacial development to explore the spatial-temporal expression pattern. Furthermore, we generated morpholino based knockdown model of ltbp1 to study the craniofacial phenotype. Results: WISH of ltbp1 was mainly detected in the mandibular jaw region, brain trunk, and internal organs such as pancreas and gallbladder. And ltbp1 colocalized with both sox9a and ckma in mandibular region. Morpholino based knockdown of ltbp1 results in severe jaw malformation. Alcian blue staining revealed severe deformity of Meckel's cartilage along with the absence of ceratobranchial. Three-dimension measurements of ltbp1 morphants jaws showed decrease in both mandible length and width and increase in open mouth distance. Expression of cartilage marker sox9a and muscle marker ckma was decreased in ltbp1 morphants. Conclusions: Our experiments found that ltbp1 was expressed in zebrafish mandibular jaw cartilages and the surrounding muscles. The ltbp1 knockdown zebrafish exhibited phenotypes consistent with Ltbp1 knockout mice. And loss of ltbp1 function lead to significant mandibular jaw defects and affect both jaw cartilages and surrounding muscles.

Associations of IL-1, 6, and 10 Gene Polymorphisms with Susceptibility to Recurrent Aphthous Stomatitis: Insights from a Meta-Analysis.

AIM: To determine if there are significant associations between polymorphisms of the IL-1, IL-6, and IL-10 genes and susceptibility to recurrent aphthous stomatitis (RAS). METHODS: The PubMed, Embase, and Web of Science databases were searched for all eligible studies using both medical subheadings and free terms through December 2016. A total of 226 citations were retrieved. Odds ratios were used to quantitatively evaluate the associations of IL-1, IL-6, and IL-10 gene polymorphisms with RAS risk. A meta-analysis was performed, and heterogeneity, sensitivity, and subgroup analyses were carried out to clarify and validate the pooled results. RESULTS: A total of 11 studies were identified that met the inclusion criteria and were included in the meta-analysis. This current systematic review indicated that the IL-1b+3954 C/T polymorphism was significantly associated with an elevated risk of RAS onset for all inheritance models, except for the dominant model. For the IL-10-592 C/A polymorphism, protective associations with RAS were found using both the additive and recessive models, while it increased the risk of RAS in the codominant model. In Asian populations, the IL-10-1082 G/A polymorphism was associated with a protective effect for RAS using the allelic, additive, and recessive models. The IL-6-174 G/C polymorphism was not statistically associated with RAS risk. CONCLUSION: The IL-1b+3954 C/T polymorphism significantly increases RAS risk. In addition, the IL-10-1082 G/A polymorphism provided protective effects for RAS in the Asian population.

Induction of reprogramming of human amniotic epithelial cells into iPS cells by overexpression of Yap, Oct4, and Sox2 through the activation of the Hippo-Yap pathway.

The present study has reported a novel method for producing induced pluripotent stem (iPS) cells. Primary human amniotic epithelial cells (HuAECs) were isolated from the amniotic membranes of pregnant women who received Cesarean sections. These cells were infected with retroviruses carrying octamer-binding transcription factor 4 (Oct4), (sex determining region Y)-box 2 (Sox2) and Yes-associated protein (Yap) (OSY). Following in vitro culture for ~14 days, epithelial-like HuAECs exhibited several iPS clone-like cell colonies (OSY-iPS). These cell clones presented positive alkaline phosphatase features and expressed high levels of embryonic stem cell-like markers (Nanog homeobox, Sox2, Oct4, reduced expression protein 1, and SSES3/4). Additionally, epigenetic analysis results indicated that the methylation of CpG islands on endogenous Oct4 and Sox2 promoters was reduced in OSY-iPS cells. Furthermore, the majority of the histone H3 at lysine 9 sites that interacted with the Oct4 and Sox2 promoters were acetylated, suggesting that the transcription activities of the above two transcription factors significantly increased. In vivo and in vitro induced differentiation experiments demonstrated that OSY-iPS could develop into embryoid bodies in vitro, and express numerous cellular markers in the three germ layers. Furthermore, OSY-iPS could form teratomas in immunodeficient mice. The pathological detection results suggest that these teratomas contain numerous types of cells from the three germ layers. However, the results from the quantitative polymerase chain reaction and western blot analyses suggest that the Hippo-Yap signaling pathway was significantly activated in OSY-iPS cells. In conclusion, a novel method for iPS induction was established in the present study. HuAECs were successfully induced to reprogram iPS cells through the introduction of OSY to activate the Hippo-Yap signaling pathway.

[Effects of orthodontic force on tumor necrosis factor alpha protein expression in the inflammatory periodontal tissues].

OBJECTIVE: To explore the combined effects of orthodontic force and inflammation on the remodelling of periodontal tissues. METHODS: The upper first molars underwent mesial orthodontic force on 48 rats suffering experimental periodontitis and 48 rats injected lipopolysaccharide, respectively. RESULTS: The TNF-alpha protein expression in the compressed periodontal tissues fluctuated during 0, 2, 12 hours and 2, 7, 14 days stages, the OD value got to the peak in the compressed periodontal tissues in 2 days. CONCLUSION: The mechanical remodelling effects were hindered due to the circumstance of acute or chronic inflammation. The research suggests that the orthodontic treatment to adult patients with periodontal inflammation should be taken carefully.

[Association of estrogen receptor gene polymorphisms and primary trigeminal neuralgia].

OBJECTIVE: To investigate the association of estrogen receptor (ER) gene polymorphism and primary trigeminal neuralgia. METHODS: By polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), ER gene polymorphism was analyzed in 20 trigeminal neuralgia (TR) patients and 20 control individuals, and the distribution of ER genotype was compared in TR group and control group. RESULTS: There was no significant difference in frequencies of allele and genotype in XbaI or PvuII polymorphism or XbaI with PvuII polymorphisms together between TR group and control group (P > 0.05). The genotypic distribution of Xx or PpXx in TR group was higher than control group, and it was contary to xx, ppxx or Ppxx in TR group and control group. CONCLUSION: XbaI or PvuII polymorphism may be related to TR. Women with PpXx genotype may be a dangerous factor to primary trigeminal neuralgia.