Application and progress of small extracellular vesicles in periodontal and pulp regeneration北大核心

BACKGROUND: Small extracellular vesicles are important components of paracrine pathways. In recent years, the application of small extracellular vesicles in oral tissue regeneration attracted wide attention. OBJECTIVE: To review the role and application of small extracellular vesicles in periodontal and pulp tissue regeneration. METHODS: PubMed, Web of Science, CNKI and Wanfang databases were searched for relevant articles published in the past ten years. The retrieval MeSH Terms or key words were “small extracellular vesicles, exosomes, pulp stem cells, periodontal regeneration, bone regeneration, pulp regeneration, regenerative endodontics, revascularization” in Chinese and English, respectively. After removal of poorly related, outdated, and duplicate studies by reading the title and abstract, 71 articles were finally included in result analysis. RESULTS AND CONCLUSION: (1) Small extracellular vesicles were secreted by many kinds of cells, participated in intercellular communication and mediated immune response. Small extracellular vesicles have a great application potential in tissue regeneration. (2) Small extracellular vesicles play an important role in periodontal tissue repair and regeneration. Small extracellular vesicles can regulate periodontal inflammation and promote periodontal ligament and surrounding bone tissue regeneration. (3) Small extracellular vesicles improve dental stem cells to regenerate functional pulp-dentin complexes. © 2023, Chinese Journal of Tissue Engineering Research. All rights reserved.     

Electroacupuncture for chronic pain in a model of knee arthritis北大核心

BACKGROUND: Acupuncture has been found to be effective for alleviating low back pain and acute pain due to knee arthritis, but its effect on chronic pain is under discussion. OBJECTIVE: To investigate the mechanism underlying electroacupuncture (EA) alleviating chronic pain in a New Zealand rabbit model of knee arthritis. METHODS: (1) Thirty-two New Zealand rabbits were selected, and the knee osteoarthritis model was established by injecting 4% papain into the knee articular cavity of rabbit’s bilateral hind limbs. The model rabbits were randomly divided into four groups (n=8 per group): normal saline plus EA, normal saline plus sham EA, nor-Binaltorphimine (nor-BNI) plus EA, and nor-BNI plus sham EA groups. The dosage of nor-BNI was 1 mg/kg, once daily, for consecutive 3 days. 30-minute EA was given at 2 hours after administration, once daily, until the day the rabbits were killed. Sham EA indicated no given electric current. The behaviors of the lower limbs were evaluated by Basso, Beattie, Bresnahan scores. The rabbits were respectively killed at 1, 3, 5 and 7 days after administration, the spinal cord was separated, and then fixed with formaldehyde. The expression levels of interleukin-17, interleukin-17 receptor A and NR1 in the spinal cord tissues were detected by immunofluorescence. (2) The other 24 New Zealand rabbits were randomly divided into model and control groups (n=12 per group), and the knee osteoarthritis model was established in the former group. Afterwards, the two groups were randomized into two subgroups, followed by given the intrathecal administration of normal saline, or 2 μg interleukin-17 antibody serum dissolved in 10 μL normal saline, once daily, for consecutive 3 days. The behaviors of the lower limbs were evaluated by Basso, Beattie, Bresnahan scores, and the expression levels of p-NR1 and interleukin-17 receptor were detected by western blot assy. RESULTS AND CONCLUSION: The Basso, Beattie, Bresnahan scores in the nor-BNI plus EA group were significantly increased, while the expression levels of interleukin-17, interleukin-17 receptor A and NR1 in the spinal cord tissues were significantly decreased (P < 0.05). The expression level of NRI did not differ significantly between nor-BNI plus EA and nor-BNI plus sham EA groups (P > 0.05). After administration of interleukin-17 antibody serum, the Basso, Beattie, Bresnahan scores in the model group was significantly increased, and the expression levels of interleukin-17 and NR1 in the spinal cord tissues were significantly decreased, but still significantly higher than those in the control subgroups (P < 0.05). These results suggest that chronic pain in knee arthritis is the result of an increase in the expression level of NRI induced by interleukin-17. EA can remarkably improve the pain in the model rabbits of knee arthritis by downregulating interleukin-17 in the spinal cord tissues, rather than interleukin-17 receptor. © 2017, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

Analysis of isodicentric Ph chromosomes in chronic myeloid leukemia blast crisis北大核心CSCD

Objective To explore the genetic and clinical characteristics of isodicentric Ph chromosomes [idic(Ph)] in lymphoid blast crisis of chronic myeloid leukemia (CML-BLC). Methods Bone marrow aspirates of 2 patients withCML-BLC were analyzed by R banding after 24 hours of culturing. Genomic copy number variations (CNV) wereanalyzed by single nucleotide polymorphism array (SNP array) in case 1. The results were confirmed withfluorescence in situ hybridization (FISH). Variations of acute lymphoblastic leukemia-related genes includingCDKN2A/AB and PAX5 were detected by multiplex ligation-dependent probe amplication (MLPA). Results Deletionsand duplications on derivative chromosome 9 detected by FISH were confirmed by SNP array analysis. Thedistances between the BCR/ ABL fusion signals on the idic(Ph) chromosomes in the two patients have differedgreatly. The idic(Ph) in the second patient was supposed to be formed by two Ph chromosomes joined at their qterminals, where as the idic(Ph) in the first patient have been shown to be fused at the satellite regions oftheir p arms. Conclusion The idic(Ph) chromosomes presented in CML-BLC may predict resistance to Imatinib andresponse to Dasatinib.     

β1-Adrenoceptor antibody-induced increase in soluble CD40 ligand release in chronic periodontitis patients: role of prostaglandin E2

In this paper, we demonstrate that circulating antibodies from chronic periodontitis patients reacting with atrial β(1)-adrenoceptors (β(1)-ARs) act as an inducer of soluble CD40 ligand (sCD40L) release and prostaglandin E(2) (PGE(2)) generation. By enzyme-linked immunosorbent assay using β(1) synthetic peptide (with an amino acid sequence identical to the second loop of human myocardial β(1)-ARs) as a coating antigen, we demonstrated reactivity against the second extracellular loop on human myocardial β(1)-ARs. This autoantibody present in the serum of chronic periodontitis patients was significantly correlated with the release of sCD40L and PGE(2). The release of sCD40L was blunted by atenolol, SP600125 and β(1) synthetic peptide, and PGE(2) generation was inhibited by DuP 697 and slightly by FR122049. The effects of the antibody incubated with isolated rat atria upregulated sCD40L release with an increase of PGE(2) production and c-Jun N-terminal kinase phosphorylation. These results indicate that in chronic periodontitis patients, there is a positive association between sCD40L release and PGE(2) generation via the action of β(1)-AR antibodies.     

Inhalation of bone marrow mesenchymal stem cells-derived exosomes alleviates inflammatory injury in chronic obstructive pulmonary disease北大核心

BACKGROUND: Many studies have demonstrated that exosomes derived from bone marrow mesenchymal stem cells show strong repair and regeneration ability in various models of respiratory inflammation and disease injury, but there are few studies on chronic obstructive pulmonary disease, and no studies have applied aerosolized inhalation of exosomes in model experiments of chronic obstructive pulmonary disease. OBJECTIVE: To investigate the therapeutic effects of exosomes derived from rat bone marrow mesenchymal stem cells on inflammation and lung injury in rats with chronic obstructive pulmonary disease by aerosol inhalation, and to determine the optimal therapeutic dose. METHODS: Rat bone marrow mesenchymal stem cells were isolated and cultured in vitro, and exosomes were extracted and identified. The rat model of chronic obstructive pulmonary disease was established by lipopolysaccharide combined with smoking for 28 days. Then low dose (0.5×108 particles/kg), medium dose (1.0×108 particles/kg), and high dose (1.5×108 particles/kg) exosome aerosol treatment and exosome (1.5×108 particles/kg) were given by tail vein injection. The model group was atomized with 1 mL PBS, while the control group was not molded with 1 mL PBS. Continuous atomization or injection was conducted for 5 days, and the test was started on the second day after the last atomization or injection treatment. The lung function indexes were tested by small animal pulmonary function instrument. The levels of interleukin-1β and tumor necrosis factor-α in bronchoalveolar lavage fluid and serum were detected by ELISA. The changes of lung tissues were assessed histologically by hematoxylin-eosin staining and Masson staining. RESULTS AND CONCLUSION: (1) The exosomes of bone marrow mesenchymal stem cells showed elliptic double-membrane vesicles under transmission electron microscopy, which were typical cup-shaped. Particle size analysis indicated that the peak diameter of exosomes was 91.7 nm, accounting for 97.3%, and the particle concentration was 3.3×109 L-1. In addition, surface proteins CD9 and CD63 were highly expressed. (2) Compared with caudal vein injection of exosome, aerosol inhalation of exosome significantly improved lung function, collagen deposition and pathological changes of lung tissue in rats with chronic obstructive pulmonary disease, and significantly decreased the levels of interleukin-1β and tumor necrosis factor-α in bronchoalveolar lavage fluid and serum. The low exosome dose had the most significant therapeutic effect. (3) These results suggest that inhalation of exosomes from bone marrow mesenchymal stem cells can reduce inflammatory injury in chronic obstructive pulmonary disease and the optimal dose may be 0.5×108 particles/kg. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Osteopontin promotes chondrocyte proliferation in osteoarthritis北大核心

BACKGROUND: Osteopontin, a kind of extracellular matrix glycoprotein, has been found to participate in synthesis and catabolism of osteoarthritic chondrocyte extracellular matrix. However, the effect of osteopontin on the proliferation ability of osteoarthritic chondrocytes is little reported. OBJECTIVE: To investigate the effect of osteopontin on the chondrocyte proliferation in human knee osteoarthritis. METHODS: Cartilage samples were obtained from the patients with knee osteoarthritis undergoing knee arthroplasty at the Xiangya Hospital from January 2012 to June 2012. The chondrocytes were isolated and cultured, and then divided into four groups: blank control, osteopontin, Con-shRNA and osteopontin-shRNA groups. The cell proliferation was detected by MTT and BrdU assays. RESULTS AND CONCLUSION: After transfection of osteopontin-shRNA lentivirus, the infection rate was up to 80%. Compared with the blank control group, osteopontin group showed a significant increase in the absorbance value of osteoarthritic chondrocytes, while after osteopontin-shRNA lentivirus transfection, the absorbance value was significantly decreased (both P < 0.05). Additionally, after osteopontin-shRNA transfection, the expression level of osteopontin was significantly downregulated (P < 0.05). To conclude, osteopontin can promote the proliferation of osteoarthritic chondrocytes, which is considered as a new treatment target for osteoarthritis. © 2017, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

The role of cathepsin C in Papillon-Lefèvre syndrome, prepubertal periodontitis, and aggressive periodontitis

We have previously reported that loss-of-function mutations in the cathepsin C gene (CTSC) result in Papillon-Lefèvre syndrome, an autosomal recessive condition characterized by palmoplantar keratosis and early-onset, severe periodontitis. Others have also reported CTSC mutations in patients with severe prepubertal periodontitis, but without any skin manifestations. The possible role of CTSC variants in more common types of non-mendelian, early-onset, severe periodontitis ("aggressive periodontitis") has not been investigated. In this study, we have investigated the role of CTSC in all three conditions. We demonstrate that PLS is genetically homogeneous and the mutation spectrum that includes three novel mutations (c.386T>A/p.V129E, c.935A>G/p.Q312R, and c.1235A>G/p.Y412C) in 21 PLS families (including eight from our previous study) provides an insight into structure-function relationships of CTSC. Our data also suggest that a complete loss-of-function appears to be necessary for the manifestation of the phenotype, making it unlikely that weak CTSC mutations are a cause of aggressive periodontitis. This was confirmed by analyses of the CTSC activity in 30 subjects with aggressive periodontitis and age-sex matched controls, which demonstrated that there was no significant difference between these two groups (1,728.7 +/- SD 576.8 micro moles/mg/min vs. 1,678.7 +/- SD 527.2 micro moles/mg/min, respectively, p = 0.73). CTSC mutations were detected in only one of two families with prepubertal periodontitis; these did not form a separate functional class with respect to those observed in classical PLS. The affected individuals in the other prepubertal periodontitis family not only lacked CTSC mutations, but in addition did not share the haplotypes at the CTSC locus. These data suggest that prepubertal periodontitis is a genetically heterogeneous disease that, in some families, just represents a partially penetrant PLS.     

Application of graphene-based nanomaterials in stem cells北大核心

BACKGROUND: As a kind of newly-developing nanomaterial, graphene has been used in many fields. Many recent studies have found that graphene-based nanomaterials can affect the biological behaviors of stem cells. OBJECTIVE: To review the application and progress of graphene-based nanomaterials in stem cells. METHODS: We searched the articles about the application of graphene-based nanomaterials in stem cells published in PubMed, Web of Science, and CNKI databases with the search terms “graphene, nanomaterials, stem cell” in English and Chinese. Finally, 57 articles met the criteria for review. RESULTS AND CONCLUSION: Graphene-based nanomaterials have good stability and corrosion resistance, high mechanical strength, good biocompatibility, which are accepted as one of the most promising nanomaterials in biomedicine. Stem cells are undifferentiated cells that can differentiate into various mature cells in human body, which have a broad application prospect in tissue engineering, regenerative medicine and other fields. Many recent studies have applied graphene-based nanomaterials to stem cell research and found that they can affect the growth, proliferation, adhesion and differentiation of stem cells, and these nanomaterials may affect the biological behavior of stem cells by regulating the expression of related genes and various signaling pathways. However, graphene-based nanomaterials have biological toxicity, which restrict their application in biological aspects. Moreover, most researches only involved cellular level, and it needs further animal studies and in vivo experimental researches. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Natural killer cell–derived extracellular vesicles in cancer therapy

Cancer is a major cause of death in the industrialized world. New therapies are constantly being developed in order to reduce morbidity and mortality. NK cell–based cellular therapies have shown effect against haematological malignancies, but it has been difficult to target solid tumours due to low NK cell infiltration of the tumour and efficient tumour evasion strategies. NK cells release extracellular vesicles that naturally contain cytolytic proteins and tumour-targeting molecules. These vesicles can directly interact with and kill malignant cells, and their small size could allow more efficient extravasation into the tumour tissue. Extracellular vesicles are also less sensitive to the hostile tumour microenvironment compared to cells. Based on their features, NK cell–derived extracellular vesicles represent promising novel tools in oncology. In this review, we summarize the current available literature on NK cell–derived extracellular vesicles and discuss how they may be utilized in therapy for solid tumours.     

社长的话北大核心

强制数据共享推进研究结果的可重复性：发表文章时你希望这样做吗？从2016年9月开始,Nature（《自然》杂志）和旗下12个子刊宣布了他们推出的研究结果数据分享新举措,所有被接受的研究论文,都必须提供他人能够获取研究结果相关原始数据的信息。作者需要提供获取他们结果最基本数据的方法和相关资料,可以帮助其他研究人员理解、重复、验证论文的研究发现。     

更正北大核心CSCD

发表于本刊2022年12月第36卷第12期1060页的文章《CircPTPN22作为miR-766-3p分子海绵促进类风湿关节炎病理进程》,摘要处“ROC分析提示circPTPN22是RA患者的潜在诊断生物标志物(AUC=0.7025)”和“ROC分析提示miR-766-3p的表达可以将RA患者与HCs区分开来(AUC=0.9125)”两处的AUC值对应关系反了,circPTPN22的AUC值应为0.9125,miR-766-3p的AUC值应为0.7025。     

更正北大核心CSCD

本刊2008年第24卷第4期483页"大鼠未成熟树突状细胞体外分离、扩增与鉴定"一文图1应为:a)Morphology of immature DCs showing large clusters(arrow)after 8 days culture with GM-CSF and IL-4(×200);b)Immature DCs showing a typical short dendritic morphology,with centric nucleus(×6 000).图1未成熟树突状细胞的形态及超微结构Fig 1 Morphology and microstructure of immature BMDCs     

Extracellular matrix proteins in intrathymic T-cell migration and differentiation?

Intrathymic T-cell migration and differentiation is not completely understood. Here, Wilson Savino and colleagues argue that certain interactions between differentiating thymocytes and thymic epithelial cells are mediated by extracellular matrix proteins and that these interactions influence intrathymic migration events and thymocyte differentiation.