Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure / 国际口腔科学杂志·英文版

The failure rate of dental implantation in patients with well-controlled type 2 diabetes mellitus (T2DM) is higher than that in non-diabetic patients. This due, in part, to the impaired function of bone marrow mesenchymal stem cells (BMSCs) from the jawbone marrow of T2DM patients (DM-BMSCs), limiting implant osseointegration. RNA N6-methyladenine (m6A) is important for BMSC function and diabetes regulation. However, it remains unclear how to best regulate m6A modifications in DM-BMSCs to enhance function. Based on the "m6A site methylation stoichiometry" of m6A single nucleotide arrays, we identified 834 differential m6A-methylated genes in DM-BMSCs compared with normal-BMSCs (N-BMSCs), including 43 and 790 m6A hypermethylated and hypomethylated genes, respectively, and 1 gene containing hyper- and hypomethylated m6A sites. Differential m6A hypermethylated sites were primarily distributed in the coding sequence, while hypomethylated sites were mainly in the 3'-untranslated region. The largest and smallest proportions of m6A-methylated genes were on chromosome 1 and 21, respectively. MazF-PCR and real-time RT-PCR results for the validation of erythrocyte membrane protein band 4.1 like 3, activity-dependent neuroprotector homeobox (ADNP), growth differentiation factor 11 (GDF11), and regulator of G protein signalling 2 agree with m6A single nucleotide array results; ADNP and GDF11 mRNA expression decreased in DM-BMSCs. Furthermore, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that most of these genes were enriched in metabolic processes. This study reveals the differential m6A sites of DM-BMSCs compared with N-BMSCs and identifies candidate target genes to enhance BMSC function and improve implantation success in T2DM patients.

miR-140-3p enhanced the osteo/odontogenic differentiation of DPSCs via inhibiting KMT5B under hypoxia condition / 国际口腔科学杂志·英文版

Human dental pulp stem cells (DPSCs) have emerged as an important source of stem cells in the tissue engineering, and hypoxia will change various innate characteristics of DPSCs and then affect dental tissue regeneration. Nevertheless, little is known about the complicated molecular mechanisms. In this study, we aimed to investigate the influence and mechanism of miR-140-3p on DPSCs under hypoxia condition. Hypoxia was induced in DPSCs by Cobalt chloride (CoCl

Novel targets for ischemia reperfusion injury therapy in the liver / 中华肝胆外科杂志

Liver ischemia-reperfusion injury (IRI) is a major complication of hemorrhagic shock, liver transplantation, and other liver surgeries. It’s important to study the targets towards liver IRI for preventing and mitigating the clinical renal injury. It has been reported that the peroxisome proliferator activated receptor gamma (PPARγ) protects the liver against IRI by targeting family with sequence similarity 3 member A (FAM3A). At the meantime, noncoding RNAs, including lncRNAs and miRNAs, have also been reported to play important roles on the process of hepatic IRI. This review briefly discussed the roles and mechanisms of PPARγ, FAM3A and noncoding RNAs in liver IRI, to find potential targets of gene therapy, aiming to prevent and mitigate the liver IRI as well as to improve postoperative liver function.

Novel targets for ischemia reperfusion injury therapy in the liver / 中华肝胆外科杂志

Liver ischemia-reperfusion injury(IRI)is a major complication of hemorrhagic shock,liver transplantation.and other liver surgeries.It's important to study the targets towards liver IRI for preventing and mitigating the clinical renal injury.It has been reported that the peroxisome proliferator activated receptor gamma(PPARγ)protects the liver against IRI by targeting family with sequence similarity 3 member A(FAM3 A).At the meantime,noncoding RNAs,including lncRNAs and miRNAs,have also been reported to play important roles on the process of hepatic IRI.This review briefly discussed the roles and mechanisms of PPAR3,,FAM3A and noncoding RNAs in liver IRI,to find potential targets of gene ther-apy,aiming to prevent and mitigate the liver IRI as well as to improve postoperative liver function.

Local icariin application enhanced periodontal tissue regeneration and relieved local inflammation in a minipig model of periodontitis / 国际口腔科学杂志·英文版

Periodontitis is an inflammatory autoimmune disease. Treatment should alleviate inflammation, regulate the immune reaction and promote periodontal tissue regeneration. Icariin is the main active ingredient of Epimedii Folium, and it is a promising compound for the enhancement of mesenchymal stem cell function, promotion of bone formation, inhibition of bone resorption, alleviation of inflammation and regulation of immunity. The study investigated the effect of icariin on periodontal tissue regeneration in a minipig model of periodontitis. The minipig model of periodontitis was established. Icariin was injected locally. The periodontal clinical assessment index, a computed tomography (CT) scan, histopathology and enzyme-linked immune sorbent assay (ELISA) were used to evaluate the effects of icariin. Quantitative analysis results 12 weeks post-injection demonstrated that probing depth, gingival recession, attachment loss and alveolar bone regeneration values were (3.72 ± 1.18) mm vs. (6.56 ± 1.47) mm, (1.67 ± 0.59) mm vs. (2.38 ± 0.61) mm, (5.56 ± 1.29) mm vs. (8.61 ± 1.72) mm, and (25.65 ± 5.13) mm vs. (9.48 ± 1.78) mm in the icariin group and 0.9% NaCl group, respectively. The clinical assessment, CT scan, and histopathology results demonstrated significant enhancement of periodontal tissue regeneration in the icariin group compared to the 0.9% NaCl group. The ELISA results suggested that the concentration of interleukin-1 beta (IL-1β) in the icariin group was downregulated compared to the 0.9% NaCl group, which indicates that local injection of icariin relieved local inflammation in a minipig model of periodontitis. Local injection of icariin promoted periodontal tissue regeneration and exerted anti-inflammatory and immunomodulatory function. These results support the application of icariin for the clinical treatment of periodontitis.

Investigation on the epidemic status of drinking brick-tea type fluorosis in Tibet / 中华地方病学杂志

Objective To grasp the prevalence of drinking brick-tea type fluorosis in Tibet,and to provide scientific basis for the development of prevention and control strategies.Methods Twelve counties were selected from 7 regions in Tibet.In accordance with the "Drinking Brick-Tea Type Endemic Fluorosis Monitoring Program",a total of 46 administrative villages were selected as survey points using the cluster stratified sampling method.Household water samples,tea-water samples and adult urine samples were collected,and household fluorine intake status and incidence of skeletal fluorosis in adults over 16 years old were investigated.In the rural grade primary school where the village children were concentrated,all children aged 8-12 were selected,urine samples were collected,and the prevalence of dental fluorosis was investigated.Fluoride contents in tea,water,and urine were detected by ion selective electrode method.The dental fluorosis and skeletal fluorosis were examined and judged according to the "Diagnosis of Dental Fluorosis" (WS/T 208-2011) and the "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS 192-2008),respectively.Results A total of 46 villages in 12 counties were investigated,1 992 of water samples,1 662 of tea samples,664 of children urine samples,3 186 of adult urine samples were detected;547 children aged 8-12 were examined dental fluorosis and 3 196 adults were examinea skeletal fluorosis,respectively.The water fluoride contents in all the investigated villages were less than 1.0 mg/L;the average fluoride content in brick-tea water was 6.12 mg/L,within the range of 0.11-84.00 mg/L,and the average daily brick tea fluorine intake of residents was 24.98 mg.The geometric mean of urine fluoride in children and adults was 0.76,2.28 mg/L,respectively.The prevalence rates of dental fluorosis in children and skeletal fluorosis in adults over 16 years old were 31.81％ (174/547) and 48.59％ (1 553/3 196),respectively.The children dental fluorosis index was 0.60.The detection rate of skeletal fluorosis in adults aged 36-45 was 13.37％ (69/516).Conclusions The prevalence of drinking brick-tea type fluorosis in Tibet is serious and widely distributed.In particular,the prevalence rate of skeletal fluorosis in adults is relatively high,while that of dental fluorosis in children is relatively mild.The prevention and control of drinking brick-tea type fluorosis in Tibet brook no delay.

The key factors which affect the bio-root regeneration / 中华口腔医学杂志

The morbidity of tooth missing is the highest one among all the human organ diseases. The present restorations used in clinic, including fixed bridges, removable dentures and implant prosthetics, all exhibit their own defects, and hardly to restore the whole tooth structure and function. With the development of stem cells and tissue engineering, as an alternative, tooth regeneration, aiming at the generation of a structure like nature tooth, will be the therapeutic orientation to restore the lost tooth. The dental root, which supports the crown and occlusal force, is the fundamental part for tooth function. Based on the theory of tissue engineering, bio-roots were successfully generated by using mesenchymal stem cells (MSC) in miniature pigs. But the success rate of bio-root is not too high, is urgent to be improved for future clinic application. MSC mediated bio-root regeneration is depended on the dentinogenic differentiation regulation of MSC. Up to now, many factors affect the directed differentiation of MSC and further for the success rate of bio-root, including seeding cells, scaffold, growth factors and microenvironmental niche, etc. Microenvironmental niche is the key factor for affecting the MSC characteristics and special tissue regeneration. Basically, the bio-root is regenerated in jaw, while the jaw microenvironmental niche is prone to induce MSC for osteogenic differentiation, instead of dentinogenic differentiation. How to improve the dentinogenic differentiation of MSC in jaw microenvironmental niche is the key issue for increasing the success rate of bio-root.

Gene Mapping and Mutation Identification in Patients with Primary Erythromelalgia / 中华皮肤科杂志

Objective To map the specific gene responsible for primary erythromelalgia and identify gene mutations in a Chinese family and one sporadic patient with primary erythromelalgia. Methods Geno-mic DNA was extracted from peripheral lymphocytes of the family members of the pedigree and the sporadic patient. Scanning the genes on chromosome 2q that had been identified was performed by using 6 microsatellite markers for the family members with primary erythromelalgia. Then linkage analysis and haplotype analysis were conducted. All exons of SCN9A gene were analyzed by PCR-DNA sequencing. The mutation identification was also confirmed by restriction fragment length polymorphism(RFLP). Results A maximum 2-point LOD score of 2.11 was found at a recombination fraction (? = 0.00) with markers D2S2370 and D2S2330. Recombination events were detected by markers D2S1353 and D2S2345 in this family by the haplotype analysis. There were two missense heterozygous point mutations in the 15th exon of SCN9A gene both in the family(T2573A) and the sporadic patient(T2543C), leading to the substitution of the amino acid leucine to histidine(L858H) and isoleucine to threonine(I848T), respectively. The above mutations were not found in 400 normal alleles. Conclusion It is proved that primary erythromelalgia is caused by mutations in SCN9A gene.