Hypoxia is a crucial factor with type diversity that plays an important role in stem cell transplantation. However, the effects of hypoxia on adipose-derived stem cells (ADSCs) are largely unclear in the autologous fat transplantation (AFT) model, which shows a special type of “acute-progressively resolving hypoxia.” Here, an AFT model in nude mice and a hypoxic culture model for ADSCs were combined to explore the link between hypoxia-inducible factor-1 α subunit (HIF-1α) and mitophagy under hypoxic conditions. The results showed that the activity of ADSCs in the first 7 days after grafting was the key stage for volume retention, and the expression of HIF-1α, light chain 3 beta (LC3B), and Beclin1 in ADSCs increased during this period. We also found that hypoxia for longer than 48 h damaged the differentiation and mitochondrial respiration of ADSCs in vitro , but hypoxia signals also activate HIF-1α to initiate mitophagy and maintain the activities of ADSCs. Pre-enhancing mitophagy by rapamycin effectively improves mitochondrial respiration in ADSCs after grafting and ultimately improves AFT outcomes.
After more than a century of development, autologous fat transplantation (AFT), a repair method for soft tissue defects and deformities, has the advantages of being simple, rapid, effective and safe, and it is increasingly favoured by plastic surgeons. This article reviews the developmental history of AFT, analyses its clinical application status in the oral and maxillofacial regions, and provides a preliminary summary and discussion of the research progress related to AFT. The hope is that that this technique could be widely applied for oral and maxillofacial diseases as well as facial rejuvenation indications. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Due to its various advantages, including minimal invasiveness, high safety and sufficient availability, autologous fat transplantation has been widely used in the repair of soft tissue defects in the oral and maxillofacial regions; however, its high postoperative fat absorption rate remains a major problem for clinicians. In recent years, it has been found that the high levels of growth factors and dense threedimensional network structure in Platelet-Rich Fibrin (PRF) provide a suitable microenvironment for the growth of fat in transplantation areas, which can promote the adhesion and proliferation of adipose-derived stem cells. PRF is an ideal material to solve the problem of a high fat absorption rate. This article reviews the efforts of clinicians to reduce the absorption rate of fat transplantation, analyzes the effect of PRF on adipose stem cells, summarizes the clinical application of PRF in oral and maxillofacial fat transplantation, and preliminarily summarizes and discusses some problems existing in PRF in oral and maxillofacial fat transplantation. The hope is that PRF will be more widely used in oral and maxillofacial fat transplantation.
MicroRNAs (miRNAs) are implicated in the pathogenesis of oral squamous-cell carcinoma (OSCC). miR-101 is involved in the development and progression of OSCC, but the biological functions and underlying molecular mechanisms of this miRNA remain largely unknown. In this study, we showed that miR-101 was underexpressed in OSCC tissues and cell lines. miR-101 downregulation was inversely correlated with zinc finger E-box binding homeobox 1 (ZEB1) expression, lymph-node metastasis, and poor prognosis in OSCC patients. Enhanced expression of miR-101 significantly inhibited OSCC cell proliferation, apoptosis resistance, migration and invasion in vitro, and suppressed tumor growth and lung metastasis in vivo. Bioinformatics analyses showed that miR-101 directly targeted ZEB1, as confirmed by a dual-luciferase reporter assay. The inhibitory effects of miR-101 on OSCC growth and metastasis were attenuated and phenocopied by ZEB1 overexpression and knockdown, respectively. Overall, our findings indicated that miRNA-101 reduced OSCC growth and metastasis by targeting ZEB1 and provided new evidence of miR-101 as a potential therapeutic target for OSCC patients.
Engineered bone substitutes are being extensively explored in response to growing demand. However, the angiogenesis that occurs during bone formation is often overlooked in scaffold design. In this novel study, we incorporated two small interfering RNAs (siRNAs), ie, small interfering RNA targets casein kinase 2 interaction protein 1 (siCkip-1) and small interfering RNA targets soluble VEGF receptor 1 (siFlt-1), which can promote osteogenesis and angiogenesis, into a chitosan sponge. This scaffold could maintain siRNAs for over 2 weeks in neutral phosphate-buffered saline and degraded rapidly in the presence of lysozyme. The chitosan sponge with siCkip-1 and siFlt-1 in vitro bioactivity was investigated using mesenchymal stem cells. Target genes were significantly suppressed, and osteocalcin, alkaline phosphatase, and vascular endothelial growth factor were significantly upregulated. Alizarin Red staining revealed that mineralization of the extracellular matrix was markedly enhanced by dual transfection. Further analysis by immunofluorescence confirmed that the siRNA-modified scaffold simultaneously improved the expression of osteocalcin and von Willebrand factor. In vivo testing in a skull critical-size defect model showed marked bone regeneration in rats treated with siCkip-1 and siFlt-1. In conclusion, chitosan sponge containing osteogenic and angiogenic siRNAs may be used as a scaffold for bone regeneration. The dual siRNA concept may also be useful in the biofunctionalization of other materials.
Aim: To probe into the feasibility constructing a simple trauma scoring method based on codes of International Classification of Diseases(ICD) and investigate the structural frame of the model for trauma scoring of patients with maxillofacial injuries. Methods: Totally 644 patients with maxillofacial injuries were selected from the Stomatological Hospital, Fourth Military Medical University from May 1998 to April 2002. By using the conversion table of ICD codes and Abbreviated Injury Scale(AIS) values, the codes of ICD in patients were conversed into AIS values(ICD-NISS), and then the severity values of ICD-NISS were calculated in each patient. Factors other than ICD-NISS affecting the evaluation of injury severity were screened out and predictive model for NISS values based on AIS values was worked out by professional raters using multivariate linear regression. Results: The data in all the 644 patients were used for the result analysis. 1 Three variables and four interaction terms were entered the predicting model of trauma severity scores based on the selected ICD-NISS, and its basic parameters were worked out. 2 Validation result showed that the predicted trauma severity scores were consistent with the NISS scores based on AIS values worked out by professional raters to some extent with a linear correlation coefficient of 0.392 2(P < 0.0001). Conclusion: A primary scheme of simple trauma scoring method based on ICD codes is obtained and it is effective in evaluating injury severity for patients with maxillofacial injuries.