Antibacterial Chitosan Coating on Nano-hydroxyapatite/Polyamide66 Porous Bone Scaffold for Drug Delivery

This study describes a new drug-loaded coating scaffold applied in infection therapy during bone regeneration. Chitosan (CS) containing antibacterial berberine was coated on a nano-hydroxyapatite/polyamide66 (n-HA/PA66) scaffold to realize bone regeneration together with antimicrobial properties. The porous scaffold was fabricated using the phase-inversion method with a porosity of about 84% and macropore size of 400–600 μm. The morphology, mechanical properties and drug-release behavior were investigated at different ratios of chitosan to berberine. The results show that the elastic modulus and compressive strength of the coated scaffolds were improved to 35.4 MPa and 1.7 MPa, respectively, about 7 times and 3 times higher than the uncoated scaffolds. After a burst release of berberine within the first 3 h in PBS solution, a continuous berberine release can last 150 h, which is highly dependent on the coating concentration and suitable for antibacterial requirement of orthopaedic surgery. The bactericidal test confirms a strong antibiotic effect of the delivery system and the minimum inhibitory concentration of the drug is 0.02 mg/ml. Moreover, in vitro biological evaluation demonstrates that the coating scaffolds act as a good matrix for MG63 adhesion, crawl, growth and proliferation, suggesting that the antibacterial delivery system has no cytotoxicity. We expect the drug-delivery system to have a potential application in bone regeneration or defect repair.     

口腔癌合并全身系统性疾病患者的多学科协作诊疗模式专家共识

近年来，随着双向转诊、分级诊疗和医联体的建立，大型综合医院承担急危重症和疑难疾病诊疗的功能定位日益凸显，来诊的口腔癌患者常伴有全身情况复杂的系统性疾病，传统的单一诊疗模式难以达到医疗需求。为此，多学科协作诊疗（MDT）模式应运而生并在实践中应用，取得了良好的临床效果。为了进一步规范口腔癌患者的MDT，组织专家制订了本专家共识，对诊疗流程、常见系统性疾病的诊治等给出了规范化建议，供临床医师参考。     

机器学习在颌面部囊肿及肿瘤中应用的研究进展

随着人工智能在图像识别等领域的发展，其在医学中的应用逐渐得到了重视。近年来，许多研究显示机器学习在口腔医学中应用场景广泛，尤其在颌面部囊肿及肿瘤的临床诊疗中具有较大的临床价值。本文就机器学习在颌面部囊肿及肿瘤中的应用进行综述，以期为口腔颌面部疾病的诊断提供新的方法。     

化学合成小干扰RNA对PC12细胞NgR表达的影响

目的 Nogo及Nogo-66受体(Ng R)对抑制中枢神经系统再生有重要的作用。本文主要观察化学合成Ng R特异性小干扰RNA(si RNA)对具有神经元分化潜能的克隆细胞系PC12细胞Ng R m RNA和蛋白表达的影响。方法培养大鼠肾上腺嗜铬瘤细胞PC12细胞,神经生长因子(NGF)诱导使其分化为类神经细胞,化学合成一段针对大鼠Ng R基因编码区的si RNA,用阳离子脂质体使之转染类神经细胞,转染后48 h,采用实时荧光定量PCR检测m RNA水平;并采用蛋白免疫印迹检测Ng R蛋白表达的变化,检测干扰的效果。结果荧光定量PCR结果显示:转染后48 h Ng R m RNA水平明显下降,差异具有显著性(P<0.05);同时蛋白免疫印迹结果显示,Ng R蛋白表达水平与对照组比较也降低,差异同样具有显著性(P<0.05)。结论化学合成Ng R特异性si RNA可以实现大鼠神经细胞内源性Ng R基因沉默。     

Ghrelin enhances the proliferating effect of thyroid stimulating hormone in FRTL-5 thyroid cells

Ghrelin regulates cell proliferation through the growth hormone secretagogue receptor (GHS-R). We confirmed the expression of GHS-R in FRTL-5 thyroid cells and investigated the effects of ghrelin in thyrocytes using FRTL-5 cells. Ghrelin increased intracellular calcium levels but not intracellular cyclic AMP levels. Ghrelin activated Erk within 2min, then activated Akt and STAT3. Erk phosphorylation was inhibited by the calcium inhibitor cyclopiazonic acid (CPA). Ghrelin alone did not stimulate FRTL-5 cell proliferation but enhanced the effects of thyroid stimulating hormone (TSH). Pretreatment with TSH potentiates the growth effects of ghrelin in thyroid cells, and p66Shc, a growth factor receptor adaptor protein, might mediate these synergistic effects. Ghrelin phosphorylated TSH-induced p66Shc, which was inhibited by CPA. Ghrelin did not affect the proliferation of ARO cells, which showed no increased expression of p66Shc after TSH treatment. Thus, ghrelin-induced intracellular calcium signaling enhanced the TSH-induced proliferation of thyrocytes, possibly mediated by the p66Shc pathway.     

Genetics of serum BDNF: Meta-analysis of the Val66Met and genome-wide association study

Abstract

Objectives. Lower levels of serum brain derived neurotrophic factor (BDNF) is one of the best known biomarkers of depression. To identify genetic variants associated with serum BDNF, we tested the Val66Met (rs6265) functional variant and conducted a genome-wide association scan (GWAS). Methods. In a community-based sample (N = 2054; aged 19–101, M = 51, SD = 15) from Sardinia, Italy, we measured serum BDNF concentration and conducted a GWAS. Results. We estimated the heritability of serum BDNF to be 0.48 from sib-pairs. There was no association between serum BDNF and Val66Met in the SardiNIA sample and in a meta-analysis of published studies (k = 13 studies, total n = 4727, P = 0.92). Although no genome-wide significant associations were identified, some evidence of association was found in the BDNF gene (rs11030102, P = 0.001) and at two loci (rs7170215, P = 4.8 × 10^–5 and rs11073742 P = 1.2 × 10^–5) near and within NTRK3 gene, a neurotrophic tyrosine kinase receptor. Conclusions. Our study and meta-analysis of the literature indicate that the BDNF Val66Met variant is not associated with serum BDNF, but other variants in the BDNF and NTRK3 genes might regulate the level of serum BDNF.     

Reduced hippocampal volumes in healthy carriers of brain-derived neurotrophic factor Val66Met polymorphism: Meta-analysis

Abstract

Objectives. Converging evidence suggests that the brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects brain structure. Yet the majority of studies have shown no effect of this polymorphism on hippocampal volumes, perhaps due to small effect size. Methods. We performed a meta-analysis of studies investigating the association between Val66Met BDNF polymorphism and hippocampal volumes in healthy subjects by combining standardized differences between means (SDM) from individual studies using random effect models. Results. Data from 399 healthy subjects (255 Val-BDNF homozygotes and 144 carriers of at least one Met-BDNF allele) in seven studies were meta-analysed. Both the left and right hippocampi were significantly larger in Val-BDNF homozygotes than in carriers of at least one Met-BDNF allele (SDM = 0.41, 95% Confidence Interval = 0.20; 0.62, z = 3.86, P = 0.0001; SDM = 0.41; 95% Confidence Interval = 0.20; 0.61, z = 3.81, P = 0.0001, respectively), with no evidence of publication bias. Conclusions. Healthy carriers of BDNF gene Val66Met polymorphism show bilateral hippocampal volume reduction. The effect size was small, but the same direction of effect was seen in all meta-analyzed studies. The association with the BDNF gene Val66Met polymorphism makes hippocampal volume a potential candidate for an endophenotype of disorders presenting with reduced hippocampal volumes.     

Transplantation of Nogo-66 receptor gene-silenced cells in a poly(D,L-lactic-co-glycolic acid) scaffold for the treatment of spinal cord injury

Inhibition of neurite growth,which is in large part mediated by the Nogo-66 receptor,affects neural regeneration following bone marrow mesenchymal stem cell transplantation.The tissue engineering scaffold poly(D,L-lactide-co-glycolic acid) has good histocompatibility and can promote the growth of regenerating nerve fibers.The present study used small interfering RNA to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells and Schwann cells,which were subsequently transplanted with poly(D,L-lactide-co-glycolic acid) into the spinal cord lesion regions in rats.Simultaneously,rats treated with scaffold only were taken as the control group.Hematoxylin-eosin staining and immunohistochemistry revealed that at 4 weeks after transplantation,rats had good motor function of the hind limb after treatment with Nogo-66 receptor gene-silenced cells plus the poly(D,L-lactide-co-glycolic acid) scaffold compared with rats treated with scaffold only,and the number of bone marrow mesenchymal stem cells and neuron-like cells was also increased.At 8 weeks after transplantation,horseradish peroxidase tracing and transmission electron microscopy showed a large number of unmyelinated and myelinated nerve fibers,as well as intact regenerating axonal myelin sheath following spinal cord hemisection injury.These experimental findings indicate that transplantation of Nogo-66 receptor gene-silenced bone marrow mesenchymal stem cells and Schwann cells plus a poly(D,L-lactide-co-glycolic acid) scaffold can significantly enhance axonal regeneration of spinal cord neurons and improve motor function of the extremities in rats following spinal cord injury.