益生菌辅助治疗牙周病的研究进展

牙周病是累及牙周支持组织的慢性感染性疾病。牙菌斑生物膜中的微生物及其代谢产物是其必不可少的始动因素,可导致口腔微生态失衡和宿主免疫反应,最终引起牙周病的发生发展。目前,牙周病的基础治疗主要是机械清除牙菌斑生物膜和牙石,但治疗效果具有局限性。益生菌通过产生抑菌物质、刺激局部免疫反应、与致病菌争夺黏膜受体和营养物质,从而改善口腔微生态平衡,促进牙周病的治疗。本文就近年来益生菌在牙周病治疗上的实验和临床研究、作用机制、安全性等进行综述,为将来益生菌辅助治疗牙周病的应用提供参考。     

Expression and assembly of largest foreign protein in chloroplasts: oral delivery of human FVIII made in lettuce chloroplasts robustly suppresses inhibitor formation in haemophilia A mice

Inhibitor formation is a serious complication of factor VIII (FVIII) replacement therapy for the X‐linked bleeding disorder haemophilia A and occurs in 20%–30% of patients. No prophylactic tolerance protocol currently exists. Although we reported oral tolerance induction using FVIII domains expressed in tobacco chloroplasts, significant challenges in clinical advancement include expression of the full‐length CTB‐FVIII sequence to cover the entire patient population, regardless of individual CD4⁺ T‐cell epitope responses. Codon optimization of FVIII heavy chain (HC) and light chain (LC) increased expression 15‐ to 42‐fold higher than the native human genes. Homoplasmic lettuce lines expressed CTB fusion proteins of FVIII‐HC (99.3 kDa), LC (91.8 kDa), C2 (31 kDa) or single chain (SC, 178.2 kDa) up to 3622, 263, 3321 and 852 μg/g in lyophilized plant cells, when grown in a cGMP hydroponic facility (Fraunhofer). CTB‐FVIII‐SC is the largest foreign protein expressed in chloroplasts; despite a large pentamer size (891 kDa), assembly, folding and disulphide bonds were maintained upon lyophilization and long‐term storage as revealed by GM1‐ganglioside receptor binding assays. Repeated oral gavages (twice/week for 2 months) of CTB‐FVIII‐HC/CTB‐FVIII‐LC reduced inhibitor titres ~10‐fold (average 44 BU/mL to 4.7 BU/mL) in haemophilia A mice. Most importantly, increase in the frequency of circulating LAP‐expressing CD4⁺CD25⁺FoxP3⁺ Treg in tolerized mice could be used as an important cellular biomarker in human clinical trials for plant‐based oral tolerance induction. In conclusion, this study reports the first clinical candidate for oral tolerance induction that is urgently needed to protect haemophilia A patients receiving FVIII injections.     

The Role of Ceramide Synthases in the Pathogenicity of Cryptococcus neoformans

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Whole genome DNA methylation profiling of oral cancer in ethnic population of Meghalaya,North East India reveals novel genes

Oral Squamous Cell Carcinoma (OSCC) is a serious and one of the most common and highly aggressive malignancies. Epigenetic factors such as DNA methylation have been known to be implicated in a number of cancer etiologies. The main objective of this study was to investigate physiognomies of Promoter DNA methylation patterns associated with oral cancer epigenome with special reference to the ethnic population of Meghalaya, North East India. The present study identifies 27,205 CpG sites and 3811 regions that are differentially methylated in oral cancer when compared to matched normal. 45 genes were found to be differentially methylated within the promoter region, of which 38 were hypermethylated and 7 hypomethylated. 14 of the hypermethylated genes were found to be similar to that of the TCGA-HNSCC study some of which are TSGs and few novel genes which may serve as candidate methylation biomarkers for OSCC in this poorly characterized ethnic group.     

Formation and physiological role of biosurfactants produced by hydrocarbon-utilizing microorganisms

Microbial growth on water-insoluble carbon sources such as hydrocarbons is accompanied by metabolic and structural alterations of the cell. The appearance of surface-active compounds (biosurfactants) in the culture medium or attached to the cell boundaries is often regarded as a prerequisite for initial interactions of hydrocarbons with the microbial cell. Under this point of view, biosurfactants produced by hydrocarbon-utilizing microorganisms, their structures and physico-chemical properties are reviewed. The production of such compounds is mostly connected with growth limitation in the late logarithmic and the stationary growth phase, in which specific enzymes are induced or derepressed. Addition of purified biosurfactants to microbial cultures resulted in inhibitory as well as in stimulatory effects on growth. Therefore, a more differentiated view of microbial production of surface-active compounds is proposed. Biosurfactants should not only be regarded as prerequisites of hydrocarbon uptake, but also as secondary metabolic products.     

Estimation of steady-state culture characteristics during acceleration-stats with yeasts

Steady-state culture characteristics are usually determined in chemostat cultivations, which are very time-consuming. In contrast, acceleration-stat (A-stat) cultivations in which the dilution rate is continuously changed with a constant acceleration rate are not so time-consuming, especially at high acceleration rates. Therefore, the A-stat could be advantageous to use instead of the chemostat. However, the highest acceleration rate, meaning the fastest A-stat that can be applied for estimating steady-state culture characteristics, is not known yet. Experimental results obtained with Zygosaccharomyces rouxii, an important yeast in soy sauce processes, showed that the culture characteristics during the A-stat with an acceleration rate of 0.001 h(-2) were roughly comparable to those of the chemostat. For higher acceleration rates the deviation between the culture characteristics in the A-stat and those in the chemostat obtained at the same dilution rate generally started to increase. The source of these deviations was examined by simulation for Saccharomyces cerevisiae. The simulations demonstrated that this deviation was not only dependent on the metabolic adaptation rate of the yeast, but also on the rate of change in environmental substrate concentrations during A-stats. From this work, it was concluded that an A-stat with an acceleration rate of 0.001 h(-2) is attractive to be used instead of chemostat whenever a rough estimation of steady-state culture characteristics is acceptable.     

Effects of 11-month interventions on oral cleanliness among the long-term hospitalised elderly

Objectives: This trial studied the effects of interventions on the oral cleanliness of the long‐term hospitalised elderly. Background: Oral cleanliness is mostly poor in long‐term facilities. While many agree on the importance of oral hygiene education for nursing personnel, little information and agreement exists on how to organise this education in geriatric institutions. Materials and methods: This is a longitudinal study with interventions. After a baseline clinical examination, the patient wards were divided into three groups (A, B and C) and the type of intervention was randomly assigned. In group A, dental hygienists provided oral hygiene measures for the subjects once every 3 weeks. In group B, the nursing staff first received hands‐on instructions after which they assumed responsibility for the subjects’ daily oral hygiene. Group C served as a control. Denture hygiene and dental hygiene were recorded at baseline and in the end of the 11‐month study period. In total, 130 subjects completed the interventions; their mean age was 82.9 years. Results: The best outcome in both denture and dental hygiene occurred when nursing staff at the wards took care of hygiene (group B). The increase in the proportion of those with good denture hygiene was the most prominent in group B (from 11% to 56%). The proportion of subjects with poor overall dental hygiene decreased from 61% at baseline to 57% in the end, for group B from 80% to 48%. Conclusions: Organised oral health education of the nursing staff should receive more attention.     

乳酸菌用作口服疫苗传递载体的研究

乳酸菌是食品级安全菌,利用乳酸菌为表达载体制成的口服疫苗安全无毒,能诱导机体产生有效的免疫应答和免疫耐受。乳酸菌口服疫苗通过胃肠粘膜进行抗原呈递,使用方便,而且较传统注射途径的免疫效果和依从性好,是理想的疫苗,有广阔的发展前景。     

Identification and phylogeny of ascomycetous yeasts from analysis of nuclear large subunit (26S) ribosomal DNA partial sequences

Approximately 500 species of ascomycetous yeasts, including members of Candida and other anamorphic genera, were analyzed for extent of divergence in the variable D1/D2 domain of large subunit (26S) ribosomal DNA. Divergence in this domain is generally sufficient to resolve individual species, resulting in the prediction that 55 currently recognized taxa are synonyms of earlier described species. Phylogenetic relationships among the ascomycetous yeasts were analyzed from D1/D2 sequence divergence. For comparison, the phylogeny of selected members of the Saccharomyces clade was determined from 18S rDNA sequences. Species relationships were highly concordant between the D1/D2 and 18S trees when branches were statistically well supported.