Three years of follow-up of otodental syndrome in 3-year-old Chinese boy: a rare case report.

BACKGROUND: Otodental syndrome is an exceptionally rare autosomal dominant condition characterized by a delayed eruption of posterior teeth, globodontia, lisping, and sensorineural hearing loss. In this case report, we reported a 3-year-old Chinese boy with the otodental syndrome. CASE PRESENTATION: A 3-year-old Chinese boy was referred to our hospital with complaint of no eruption of primary canines and molars. Three years follow-up showed lately erupted bulbous primary canines with hypoplastic enamel spot, globe-shaped primary molars and sensorineural hearing loss at 4 and a half-year-old age. We diagnosed otodental syndrome in the patient's mother with hearing loss at 16-year-old age. Gene sequencing and analysis of deafness-related genes GJB2, GJB3, SLC26A4, and mtDNA did not reveal any mutation or SNPs in the patient and his mother. CONCLUSIONS: This case report highlights the importance of detailed medical, dental, and family history examination, as well as multi-disciplinary teamwork for diagnosis and treatment of otodental syndrome.

The relationship between vitamin D receptor gene polymorphism and deciduous tooth decay in Chinese children.

BACKGROUND: In the present study, we explored the link between vitamin D receptor (VDR) BsmI, TaqI, ApaI and FokI gene polymorphisms with deciduous tooth decay in Chinese children. METHODS: Our study included 380 Chinese children aged 4-7 years, whose DNA sample was collected from the buccal mucosa. VDR gene polymorphisms was determined by PCR-RFLP. RESULTS: The adjusted logistic regression analysis demonstrated that BsmI containing the Bb genotype was linked with the increased risk of deciduous tooth decay (OR = 1.856, 95% CI = [1.184, 2.908], p = 0.007). However, VDR polymorphisms ApaI, TaqI and FokI were not associated with deciduous tooth decay (ApaI: OR = 0.839, 95% CI = [0.614, 1.145], p = 0.268; TaqI: OR = 1.150, 95% CI = [0.495, 2.672], p = 0.744; FokI: OR = 0.856, 95% CI = [0.616, 1.191], p = 0.356). CONCLUSIONS: Our results showed that VDR BsmI polymorphism was associated with the risk of deciduous tooth decay in Chinese children aged 4-7 years. However, the specific mechanism remains to further verify through experiment.

[Study on the antimicrobial effect of new bioactive glass against common bacteria in apical periodontitis of deciduous teeth].

PURPOSE: To study the antimicrobial effect of different concentrations of new bioactive glass(BG) on common bacteria in apical periodontitis of deciduous teeth. METHODS: The diameter (mm) of the inhibitory rings formed after treatment of Enterococcus faecalis, Porphyromonas gingivalis and Clostridium nucleatum with the new bioactive glass was detected and observed by paper diffusion method, and the minimal inhibitory concentration(MIC), minimal bactericidal concentration (MBC) and minimal biofilm eradication concentration (MBEC) of E. faecalis, P. gingivalis and C. pseudomallei were determined. The mixed plaques of the three bacteria were treated with 20, 40, 60 and 80 mg/mL of the new bioactive glass for 24 h. The results were analyzed by laser confocal microscopy. The antibacterial effect of the new bioactive glass on the mixed plaque was observed by confocal laser scanning microscopy (CLSM). Statistical analysis was performed with GraphPad Prism 10.0 software. RESULTS: The new bioactive glass showed strong antibacterial potential against the common bacteria of apical periodontitis; the MBEC of the new bioactive glass on the plaque was significantly greater than MIC and MBC of Enterococcus faecalis, Porphyromonas gingivalis and Clostridium nucleatum, and as the concentration of the new bioactive glass increased, the number of dead bacteria in the mixed plaque increased, and there was significant difference from that of the blank control group (P＜0.05). CONCLUSIONS: The novel bioactive glass shows significant antibacterial efficacy against Enterococcus faecalis, Porphyromonas gingivalis and Clostridium nucleatum, which are the common bacteria in apical periodontitis of deciduous teeth.

In vivo targeted delivery of antibodies into cancer cells with pH-responsive cell-penetrating poly(disulfide)s.

Cell-penetrating poly(disulfide)s (CPDs) are promising vehicles for cytosolic delivery of proteins. However, currently available arginine-rich CPD has rarely been reported for systemic delivery due to its "always" positive charge. Herein, we developed pH-responsive CPDIMD that executes tumor targeting delivery via protonation of imidazole groups within the acidic tumor microenvironment.

Cellular uptake of solid lipid nanoparticles and cytotoxicity of encapsulated paclitaxel in A549 cancer cells.

The aim of this study was to investigate the cellular uptake of solid lipid nanoparticles (SLN) and cytotoxicity of its paclitaxel delivery system. The conjugate of octadecylamine-fluorescein isothiocyanate (ODA-FITC) was synthesized, and used as a marker to prepare fluorescent SLN. The cellular uptakes of fluorescent SLN with different lipid material were evaluated by fluorescence microscopy and the measurement of fluorescence intensity. The order of cellular uptake ability was glycerol tristearate SLN>monostearin SLN>stearic acid SLN>Compritol 888 ATO SLN (ATO888 SLN). The cellular cytotoxicities of paclitaxel were highly enhanced by the encapsulation of lipid matrix. Due to the lower drug entrapment efficiency of glycerol tristearate SLN, monostearin SLN was considered as the best lipid material to improve the cytotoxicity of drug. The polyethylene glycol monostearate (PEG-SA) and the synthesized conjugate of folic acid-stearic acid (FA-SA) were further introduced into monostearin SLN, respectively. The PEG and folate modified SLN could enhance the cellular uptake of SLN and the cellular cytotoxicity of drug by the membrane disturb ability of PEG chains on the SLN surface and the improved endocytosis mediated by folate receptor.

Evaluation of Ion Release from Four Dental Sealants.

The purpose of this study was to determine the ion release from four commercially available pit-and-fissure sealants [3M Clinpro, 3M Concise™, BeautiSealant (BS), and GI FX-II)]. With each brand, 18 specimens were prepared. Their fluoride release in de-ionized water was measured by fluoride electrode, while the release of silicate (Si), aluminum (Al), sodium (Na), calcium (Ca), strontium (Sr), and phosphorus (P) was measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES) on days 1, 3, 7, 14, 21, and 28. The result showed that fluoride was not released from 3M Concise™. GI FX-II displayed the largest fluoride release, which, however, dropped rapidly on day 3. 3M Clinpro exhibited less fluoride release than GI FX-II and BS did. At any time during the 28-day experimental period, GI FX-II released more Na than the other sealants (P<0.001). BS ranked the second in Na release, and a small amount of Na ions was released from the 3M Clinpro and 3M Concise™ samples. Al ions were only detected from BS and GI FX-II, but not from the 3M Clinpro and 3M Concise™. Additionally GI FX-II had the largest Si release among the four brands at any time during the experimental period (P<0.001). Ca ions were detected from 3M Clinpro and 3M Concise™, but not from GI FX-II. BS released more Sr than the other sealants at any time during the experimental period (P<0.001). All the samples released similar amounts of P continuously during these 28 days. In conclusion, based on the type and the amount of ion release, BS is the best pit-and-fissure sealant among the four brands.

Lipidation of polyethylenimine-based polyplex increases serum stability of bioengineered RNAi agents and offers more consistent tumoral gene knockdown in vivo.

Recently we have established a novel approach to produce bioengineered noncoding RNA agents (BERAs) in living cells that carry target RNAi molecules (e.g., siRNA and miRNA) and thus act as "prodrugs". Using GFP-siRNA-loaded BERA (BERA/GFP-siRNA) as a model molecule, this study was to define the in vitro and in vivo knockdown efficiency of BERAs delivered by liposome-polyethylenimine nanocomplex (lipopolyplex or LPP). Compared to in vivo-jetPEI® (IVJ-PEI) and polyplex formulations, LPP offered greater protection of BERA/GFP-siRNA against degradation by serum RNases. Particle sizes and zeta potentials of LPP nanocomplex remained stable over 28 days when stored at 4 °C. Furthermore, comparable levels of BERA/GFP-siRNA were delivered by LPP and IVJ-PEI to luciferase/GFP-expressing human SK-Hep1-Luc-GFP or A549-Luc-GFP cells, which were selectively processed into target GFP-siRNA and subsequently knocked down GFP mRNA and protein levels. In addition, LPP-carried BERA/GFP-siRNA was successfully delivered into xenograft tumors and offered more consistent knockdown of tumoral GFP mRNA level in an orthotopic hepatocellular carcinoma (HCC) SK-Hep1-Luc-GFP xenograft mouse model, while IVJ-PEI formulation showed larger variation. These findings demonstrated that lipidation of polyplexes improved serum stability of biologic RNAi molecules, which was efficiently delivered to orthotopic HCC tissues to knock down target gene expression.

Preparation and characteristics of nanostructured lipid carriers for control-releasing progesterone by melt-emulsification.

Nanostructured lipid carriers (NLC) made from mixtures of solid and spatially incompatible liquid lipids were prepared by melt-emulsification. Their drug loading capacity and releasing properties of progesterone were compared with those of solid lipid nanoparticles (SLN), and the NLC prepared by solvent diffusion method. Monostearin (MS) and stearic acid (SA) were used as solid lipid, whilst the oleic acid (OA) was used as liquid lipid. Properties of carriers such as the particle size and its distribution, drug loading, drug encapsulation efficiency and drug release behavior were investigated. As a result, the drug encapsulation efficiencies were improved by adding the liquid lipid into the solid lipid of nanoparticles. The drug release behavior could be adjusted by the addition of liquid lipid, and the NLC with higher OA content showed the faster rate of drug releasing. NLC had higher efficiency of encapsulation and slower rate of drug release than those of NLC prepared by solvent diffusion method. On the other hand, the NLC with higher drug loading was obtained, though the drug encapsulation efficiency was decreased slightly due to the increase of the amount of drug. The NLC modified with polyethylene glycol (PEG) was also prepared by using polyethylene glycol monostearate (PEG-SA). It was observed that the incorporation of PEG-SA reduced the drug encapsulation efficiency, but increased the rate of drug release. A sample with almost complete drug release in 24h was obtained by modifying with 1.30mol% PEG-SA. It indicated that the modified NLC was a potential drug delivery system for oral administration.

Shell cross-linked stearic acid grafted chitosan oligosaccharide self-aggregated micelles for controlled release of paclitaxel.

Stearic acid grafted chitosan oligosaccharide (CSO-SA) with different degree of amino substitution (SD) was synthesized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. The critical micelle concentration (CMC) of CSO-SA with different SD was about 0.06, 0.04, 0.01 mg/ml, respectively. With the increase of micelle concentration, the micelle size decreased, and the zeta potential increased. On the other hand, with the increase of SD of CSO-SA, the micelle size and zeta potential decreased due to the increased hydrophobic interaction of SA and the reduced free amino groups. To increase the stability of the micelle in vivo and controll drug release, the shells of micelles were cross-linked by glutaraldehyde. By controlling the molar ratio of CSO-SA to glutaraldehyde, the cross-linking of intra-micelle could be reached, and the nanoparticle with smaller size than that of its initial micelle was obtained. Paclitaxel was then used as model drug to incorporate into the micelles, and the surfaces of the micelles were further cross-linked by glutaraldehyde to form drug loaded and shell cross-linked nanoparticles. The effects of drug loading, SD of CSO-SA and cross-link degree on the size, zeta potential, drug entrapment efficiency and in vitro drug release behavior of micelles and its cross-linked nanoparticles were investigated. The higher drug entrapment efficiencies (above 94%) were observed in all case. The charged amounts of drug did not affect the drug release behavior. The drug release rate decreased with the increase of SD of CSO-SA and cross-link degree.

Garcinia xanthones as orally active antitumor agents.

Using a newly developed strategy whose key step is the regioselective propargylation of hydroxyxanthone substrates, 99 structurally diverse Garcinia natural-product-like xanthones based on gambogic acid were designed and synthesized and their in vitro antitumor activity was evaluated. A set of 40 related compounds was chosen for determination of their physicochemical properties including polar surface area, log D7.4, aqueous solubility, and permeability at pH 7.4. In the light of the in vitro antitumor activity and the physicochemical properties, two compounds were advanced into in vivo efficacy experiments. The antitumor activity of compound 112, administered po, showed more potent in vivo oral antitumor activity than gambogic acid.

Evaluation of pluronic nanosuspensions loading a novel insoluble anticancer drug both in vitro and in vivo.

To improve the solubility, stability and the antitumor activity of a novel anticancer drug, 3-(4-bromopheny l)-2-(ethyl-sulfonyl)-6-methylquinoxaline1,4-dioxide (Q39), a poloxamer nanosuspension was developed by precipitation combined with high pressure homogenization in present study. In vitro characterizations of Q39 nanosuspension (Q39/NS), including particle size, polydispersity index (PI), morphology, crystalline, saturation solubility, stability and releases were evaluated. BABL/c nude mice bearing HepG2 cells were used as in vivo tumor models to evaluate the anti-tumor activity of Q39/NS after intravenous administration. The particle size and PI for Poloxamer188 nanosuspension (P188/NS) were (304±3) nm, and (0.123±0.005) respectively, and it was (307±5) nm and (0.120±0.007) for Poloxamer85 nanosuspension (P85/NS) correspondingly. The morphology of P188/NS was spherical shape while elliptoid shape for P85/NS. The crystalline of Q39/NS did not change as shown by the X-ray diffraction analysis. The stability of Q39/NS improved compared with the solution. The solubility of Q39 in P188/NS was 7.3 times higher than the original solubility, while it was 6 times for P85/NS. Sustained release as shown from the in vitro release test, together with the tumor-targeting as shown from in vivo NS distribution, may contribute to the enhanced in vivo antitumor activity of Q39/NS.

Stereoselective behavior of a novel biodegradable racemic ketoprofen injectable implant in rats.

The stereoselectivity of release of ketoprofen (KET) enantiomers from a biodegradable injectable implant containing racemic KET (rac-KET) was investigated in vivo. A pre-column chiral derivatization RP-HPLC method was employed to assay diastereoisomeric derivatives of R- and S-KET. The rac-KET injectable implant, once injected subcutaneously in rats, produced long-lasting plasma levels of S-KET, which were always greater than those of R-KET. The difference in enantiomer concentration was to be related to stereoselective release, due to stereoselective interaction between D,L-PLG in the implant and KET enantiomers, as well as the chiral inversion of KET in vivo. The rac-KET injectable implant provided the sustained release of S-KET with effective plasma levels maintained for about 8 wk after a single injection.