Mitochondrial dysfunction and oxidative stress damage are hallmarks of osteoarthritis (OA). Mesenchymal stem cell (MSC)-derived exosomes are important in intercellular mitochondria communication. However, the use of MSC exosomes for regulating mitochondrial function in OA has not been reported. This study aimed to explore the therapeutic effect of MSC exosomes in a three dimensional (3D) printed scaffold for early OA therapeutics. Methods : We first examined the mitochondria-related proteins in normal and OA human cartilage samples and investigated whether MSC exosomes could enhance mitochondrial biogenesis in vitro . We subsequently designed a bio-scaffold for MSC exosomes delivery and fabricated a 3D printed cartilage extracellular matrix (ECM)/gelatin methacrylate (GelMA)/exosome scaffold with radially oriented channels using desktop-stereolithography technology. Finally, the osteochondral defect repair capacity of the 3D printed scaffold was assessed using a rabbit model. Results : The ECM/GelMA/exosome scaffold effectively restored chondrocyte mitochondrial dysfunction, enhanced chondrocyte migration, and polarized the synovial macrophage response toward an M2 phenotype. The 3D printed scaffold significantly facilitated the cartilage regeneration in the animal model. Conclusion : This study demonstrated that the 3D printed, radially oriented ECM/GelMA/exosome scaffold could be a promising strategy for early OA treatment.
The "checkerboard" Dna-Dna hybridization technology was used to study the epidemiology of 18 microbial species associated with various states of periodontal health and disease, in a sample of 148 Chinese subjects never exposed to systematic dental therapeutic intervention, aged 30 to 39 and 50 to 59 years. Our aims were to: 1) describe the prevalence of these microorganisms; 2) correlate the microbiological and clinical profiles of the subjects; and 3) examine the association between the microbiological variables and the longitudinal changes of periodontal status that occurred over a preceding 10-year period. A maximum of 14 subgingival samples were obtained from each subject-1,864 in all. The frequency of occurrence of the 18 species examined was high in this Chinese population, on both the subject and the tooth site level. However, all species were not found equally capable of reaching high numbers in the subgingival samples and, as a rule, colonized heavily only limited proportions of tooth sites within each mouth. There was a profound increase of certain species such as Porphyromonas gingivalis, Treponema denticola, and Bacteroides forsythus in deep pockets or progressing sites. Multivariate techniques using the subgingival profile could effectively discriminate between deep/shallow pockets and progressing/ stable tooth sites. The microbiological variables showed an enhanced discriminating potential when classifications were performed on the individual subject level. Colonization by P. gingivalis, B. forsythus, Campylobacter rectus, and T. denticola at levels exceeding certain thresholds entailed a significantly increased probability (odds ratios > 4) for an individual subject to harbor deep pockets or progressing tooth sites.
ObjectivePre-eclampsia (PE) is one of the malignant metabolic diseases that complicate pregnancy. Gut dysbiosis has been identified for causing metabolic diseases, but the role of gut microbiome in the pathogenesis of PE remains unknown.DesignWe performed a case–control study to compare the faecal microbiome of PE and normotensive pregnant women by 16S ribosomal RNA (rRNA) sequencing. To address the causative relationship between gut dysbiosis and PE, we used faecal microbiota transplantation (FMT) in an antibiotic-treated mouse model. Finally, we determined the microbiome translocation and immune responses in human and mouse placental samples by 16S rRNA sequencing, quantitative PCR and in situ hybridisation.ResultsPatients with PE showed reduced bacterial diversity with obvious dysbiosis. Opportunistic pathogens, particularly Fusobacterium and Veillonella, were enriched, whereas beneficial bacteria, including Faecalibacterium and Akkermansia, were markedly depleted in the PE group. The abundances of these discriminative bacteria were correlated with blood pressure (BP), proteinuria, aminotransferase and creatinine levels. On successful colonisation, the gut microbiome from patients with PE triggered a dramatic, increased pregestational BP of recipient mice, which further increased after gestation. In addition, the PE-transplanted group showed increased proteinuria, embryonic resorption and lower fetal and placental weights. Their T regulatory/helper-17 balance in the small intestine and spleen was disturbed with more severe intestinal leakage. In the placenta of both patients with PE and PE-FMT mice, the total bacteria, Fusobacterium, and inflammatory cytokine levels were significantly increased.ConclusionsThis study suggests that the gut microbiome of patients with PE is dysbiotic and contributes to disease pathogenesis.
This study describes the progression of destructive periodontal disease among Chinese aged 20 to 80 with limited access to dental health facilities and minimal traditions for oral hygiene procedures. These individuals were followed for 10 years to determine whether the rates for progression of periodontal disease were markedly different than for populations with more access to oral health care. At baseline, participants had been examined for tooth mobility, plaque, calculus, gingival conditions, attachment levels, and probing depths on 4 sites of each tooth present. These probing depth and attachment level recordings were repeated at follow-up, although third molars were excluded from examination. A total of 398 persons remained dentate at follow-up. The analysis demonstrated that virtually all subjects experienced > or = 2 mm attachment loss over the 10-year period, and frequently in a large proportion of the sites present. Attachment loss > or = 3 mm was also widespread, but the distribution of persons according to the extent of > or = 3 mm attachment loss was positively skewed in all age groups. Positive skewness was even more pronounced when attachment loss of > or = 4 mm was considered. Some types of teeth, such as mandibular incisors and maxillary molars, had higher progression rates than did, for example, maxillary incisors. The mean individual attachment loss rates did not differ significantly between age groups, and were remarkably similar to those reported for populations whose access to and tradition for oral health care is widespread.
Background: Mesenchymal stem cells (MSCs) can be isolated from various tissues and can present themselves as a promising cell source for cell-based therapies. Although adipose- and bone marrow–derived mesenchymal stem cells have already been used in a considerable number of clinical trials for osteoarthritis treatment, systematic analyses from single- to bulk-cell resolution as well as clinical outcomes of these 2 MSCs are still insufficient. Purpose: To explore the characteristics and differences of adipose-derived stem cells (ADSCs) and bone marrow MSCs (BMSCs) at single- and bulk-cell levels, to study the clinical outcomes of these 2 cells on the treatment of osteoarthritis, and to provide potential guidance on the more precise clinical application of these MSCs. Study Design: Controlled laboratory study and meta-analysis. Methods: Same donor–derived ADSCs and BMSCs were isolated and cultured. Single- and bulk-cell assays were used to identify the characteristics of these 2 cells. Meta-analysis of clinical trials was done to compare the clinical therapeutic effects in osteoarthritis treatment with ADSCs and BMSCs. Results: Single-cell RNA sequencing analysis showed that the population of ADSCs showed lower transcriptomic heterogeneity when compared with BMSCs. Additionally, as compared with BMSCs, ADSCs were less dependent on mitochondrial respiration for energy production. Furthermore, ADSCs had a lower expression level of human leukocyte antigen class I antigen and higher immunosuppression capacity when compared with the BMSC population. Meta-analysis of current clinical trials of osteoarthritis treatment with MSCs consistently showed that ADSCs are more stable than BMSCs in their therapeutic effect. Conclusion: These results provide basic biological insights into human ADSCs and BMSCs at the single-cell resolution. Findings indicated that ADSCs may be a more controllable stem cell source, may be more adaptable to surviving in the hypoxic articular cavity niche, and may exhibit superiority in regulating inflammation. Based on the meta-analysis results of the different characteristics of ADSCs and BMSCs, ADSCs were implicated as being a better cell source for osteoarthritis treatment. Clinical Relevance: These results guide a more precise clinical application of adipose and bone marrow mesenchymal stem cells.
a b s t r a c tWe examine the relationship between analyst research and corporate earnings announcements to explore the relative importance of information discovery versus interpretation of previously released information. Using equity market reaction to capture information content, we find that information discovery (interpretation) dominates in the week before (after) firms announce their earnings. In addition, we find that the interpretation role increases in importance with the difficulty of financial accounting information. Analysis of all weeks surrounding earnings announcements shows that the information discovery role is overall more important. We are able to reconcile this result with the opposite finding in Francis et al. (2002). Crown 1 We use ''information content,'' ''market impact,'' and ''market reaction'' interchangeably, referring to the absolute value of abnormal returns surrounding event dates. 2 We do not follow Francis et al.'s use of the terms ''complements'' and ''substitutes'' because their usage is inconsistent with the definitions of these terms. In economics, goods X and Y are complements (substitutes) if and only if an increase in the price of X decreases (increases) the demand for Y. All of the studies in this line of inquiry look only at the quantity (and perhaps quality) of information, but not prices. 3 An example using academic research can illustrate this existence of both pre-emption and reinforcement effects. A research paper published just before another tends to pre-empt the impact of the later work, while the theories and results from one research paper can also stimulate future research. 4 We focus on quarterly earnings announcements, a type of corporate disclosure that is regular and mandatory. Other types of corporate disclosures are less suitable for this study due to various limitations. For instance, managerial disclosures are voluntary and subject to selection bias; merger announcements and bond rating announcements are less frequent and lead to less powerful tests. 5 Quarterly earnings announcements contain much more than the summary earnings number. For brevity, we often use the term ''earnings'' as short hand for the set of information contained in quarterly earnings announcements.X. Chen et al.
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