Oral Complications related to tropical infectious Diseases: an introduction and analysis of survey data.

BACKGROUNDS: The non-indigenous tropical infectious diseases that occur in the non-tropics arise from personnel communication between locals and visitors. Many of these infectious diseases involve oral complications. It is very important for practitioners to manage such cases based on a clear understanding of the association between tropical infectious diseases and oral health. In this study, we summarize the oral complications related to tropical infectious diseases and investigate the understanding of infectious disease practitioners in relation to the association between these conditions. In addition, we provide supportive advice to facilitate the oral management of tropical infectious diseases. METHODS: First, we investigate the oral complications related to tropical infectious diseases by performing an appropriate literature search. Then, we analyzed the understanding of 207 Chinese practitioners specializing in infectious diseases in relation to the association between these two conditions by applying a bespoke online questionnaire. RESULTS: Analysis revealed that the Chinese practitioners had very poor attitudes and knowledge relating to the association between tropical infectious diseases and oral health. Different backgrounds had no significant impact on the understanding of Chinese practitioners with regards to the association between tropical infectious diseases and oral health. CONCLUSION: Many oral complications are related to tropical infectious diseases. The understanding of Chinese practitioners with regards to the association between infectious disease and oral health was very inadequate. It is essential to promote publicity and education relating to infectious tropical diseases and oral health.

CircZDBF2 up-regulates RNF145 by ceRNA model and recruits CEBPB to accelerate oral squamous cell carcinoma progression via NFκB signaling pathway.

BACKGROUND: Oral squamous cell carcinoma (OSCC), as one of the commonest malignancies showing poor prognosis, has been increasingly suggested to be modulated by circular RNAs (circRNAs). Through GEO (Gene Expression Omnibus) database, a circRNA derived from ZDBF2 (circZDBF2) was uncovered to be with high expression in OSCC tissues, while how it may function in OSCC remains unclear. METHODS: CircZDBF2 expression was firstly verified in OSCC cells via qRT-PCR. CCK-8, along with colony formation, wound healing, transwell and western blot assays was performed to assess the malignant cell behaviors in OSCC cells. Further, RNA pull down assay, RIP assay, as well as luciferase reporter assay was performed to testify the interaction between circZDBF2 and RNAs. RESULTS: CircZDBF2 expressed at a high level in OSCC cells and it accelerated OSCC cell proliferation, migration, invasion as well as EMT (epithelial-mesenchymal transition) process. Further, circZDBF2 sponged miR-362-5p and miR-500b-5p in OSCC cells to release their target ring finger protein 145 (RNF145). RNF145 expressed at a high level in OSCC cells and circZDBF2 facilitated RNF145 transcription by recruiting the transcription factor CCAAT enhancer binding protein beta (CEBPB). Moreover, RNF145 activated NFκB (nuclear factor kappa B) signaling pathway and regulated IL-8 (C-X-C motif chemokine ligand 8) transcription. CONCLUSION: CircZDBF2 up-regulated RNF145 expression by sponging miR-362-5p and miR-500b-5p and recruiting CEBPB, thereby promoting OSCC progression via NFκB signaling pathway. The findings recommend circZDBF2 as a probable therapeutic target for OSCC.

N, P, O-codoped biochar from phytoremediation residues: a promising cathode material for Li-S batteries.

Environment and energy are two key issues in today's society. In terms of environmental protection, the treatment of phytoremediation residues has become a key problem to be solved urgently, while for energy storage, it tends to utilize low-cost and high specific energy storage materials (i.e. porous carbon). In this study, the phytoremediation residues is applied to the storage materials with low-cost and high specific capacity. Firstly, the phosphorous acid assisted pyrolysis of oilseed rape stems from phytoremediation is effective in the removal of Zn, Cu, Cd and Cr from the derived biochar. Moreover, the derived biochar from phytoremediation residues shows abundant porous structure and polar groups (-O/-P/-N), and it can deliver 650 mAh g-1with 3.0 mg cm-2sulfur, and keeps 80% capacity after 200 cycles when employing it as a sulfur host for lithium-sulfur (Li-S) batteries. Hence, phosphorous acid assisted pyrolysis and application in Li-S battery is a promising approach for the disposal of phytoremediation residues, which is contributed to the environmental protection as well as energy storage.

Erratum: PDLSCs Regulate Angiogenesis of Periodontal Ligaments via VEGF Transferred by Exosomes in Periodontitis: Erratum.

[This corrects the article DOI: 10.7150/ijms.40918.].

LIM Mineralization Protein-1 Enhances the Committed Differentiation of Dental Pulp Stem Cells through the ERK1/2 and p38 MAPK Pathways and BMP Signaling.

Tissue regeneration is the preferred treatment for dentin and bone tissue defects. Dental pulp stem cells (DPSCs) have been extensively studied for their use in tissue regeneration, including the regeneration of dentin and bone tissue. LIM mineralization protein-1 (LMP-1) is an intracellular non-secretory protein that plays a positive regulatory role in the mineralization process. In this study, an LMP-1-induced DPSCs model was used to explore the effect of LMP-1 on the proliferation and odonto/osteogenic differentiation of DPSCs, as well as the underlying mechanisms. As indicated by the cell counting kit-8 assay, the results showed that LMP-1 did not affect the proliferation of DPSCs. Overexpression of LMP-1 significantly promoted the committed differentiation of DPSCs and vice versa, as shown by alkaline phosphatase activity assay, alizarin red staining, western blot assay, quantitative real-time polymerase chain reaction assay, and in vivo mineralized tissue formation assay. Furthermore, inhibiting the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) pathways using specific pathway inhibitors showed that the ERK1/2 and p38 MAPK pathways attenuated the differentiation of DPSCs. Besides, the expression of BMP signaling pathway components were also determined, which suggested that LMP-1 could activate BMP-2/Smad1/5 signaling pathway. Our results not only indicated the underlying mechanism of LMP-1 treated DPSCs but also provided valuable insight into therapeutic strategies in regenerative medicine.

A novel anatomical self-locking plate fixation for both-column acetabular fractures.

PURPOSE: To compare the stability of the posterior anatomic self-locking plate (PASP) with two types of popular reconstruction plate fixation, i.e. double reconstruction plate (DRP) and cross reconstruction plate (CRP), and to explore the influence of sitting and turning right/left on implants. METHODS: PASP, DRP and CRP were assembled on a finite element model of both-column fractures of the left acetabulum. A load of 600 N and a torque of 8 N·m were loaded on the S1 vertebral body to detect the change of stress and displacement when sitting and turning right/left. RESULTS: The peak stress and displacement of the three kinds of fixation methods under all loading conditions were CRP > DRP > PASP. The peak stress and displacement of PASP are 313.5 MPa and 1.15 mm respectively when turning right; and the minimal was 234.0 Mpa and 0.619 mm when turning left. CONCLUSION: PASP can provide higher stability than DRP and CRP for both-column acetabular fractures. The rational movement after posterior DRP and PASP fixation for acetabular fracture is to turn to the ipsilateral side, which can avoid implant failure.

Investigation of the understanding on tropical infectious diseases and oral health among dental professionals in China.

BACKGROUND: With the increasing exchange of domestic and international personnel, local infections of tropical infectious diseases are continuing in tropics and imported infections are emerging in non-tropics, some of which are accompanied by oral manifestations. Therefore, it is essential for dental professionals to identify the related oral manifestations, who are working for domestic medical service, international medical assistance, peace-keeping medical service or medical support of international joint military exercises. This study aims to investigate the attitude and knowledge of Chinese dental professionals on tropical infectious diseases and oral health, and to explore the difference between different genders, education backgrounds, professional identities, professional titles and tropics working experience. METHODS: Network questionnaire was used to evaluate the knowledge and attitude of 236 Chinese dental professionals towards tropical infectious diseases and oral health. RESULTS: The scores of the participants on tropical infectious diseases and oral health were quite low. Although working experience in the tropics partially affected the understanding, there was no difference between different genders, education backgrounds, professional identities and professional titles. CONCLUSION: The understanding of dental professionals on tropical infectious diseases and oral health was insufficient. It is necessary to improve the clinical education and management specified with tropical infectious diseases and oral health.

Oral-maxillofacial adverse events related to antimalarials.

Malaria is a worldwide parasitic disease, which affects millions of lives every year. Various medications are recommended by WHO for prevention and treatment of malaria. However, adverse events caused by antimalarials were frequently reported, some of which were severe and fatal. Disorders of many organs related to antimalarials have been well recognized, whereas few studies concentrated on the relationship between antimalarials and oral-maxillofacial system health. Current review generalized the relevance of antimalarials to the health of oral-maxillofacial part and raised an urgent need to form a standard management for antimalarial-related oral-maxillofacial adverse events.

Oral manifestations related to malaria: A systematic review.

OBJECTIVE: To generalize the oral manifestations related to malaria and discuss their clinical significance for health professionals. MATERIALS AND METHODS: The bibliographic databases of Public MEDLINE, Embase, Web of Science and Scopus were employed to retrieve publications online from January 1781 to August 2019. Original research articles, clinical trials, and case reports published in English were included. RESULTS: A small number of studies reported oral manifestations of malaria (n = 29), including gingival bleeding, glossitis, oral ulcer, abnormal oral pigmentation, pericoronitis, herpes labialis, herpes gingivostomatitis, bitter taste, sore throat, Burkitt lymphoma of the jaw, alveolar bone resorption, and enamel hypoplasia. CONCLUSION: Oral manifestations may be important indicators for identification of malaria. Dental and general professionals should pay more attention to oral manifestations in malaria cases, and guide them for specialized examination, diagnosis, and management.

SHED promote angiogenesis in stem cell-mediated dental pulp regeneration.

Dental pulp, plays an indispensable role in maintaining homeostasis of the tooth. Pulp necrosis always causes tooth nutrition deficiency and abnormal root development, which leads to tooth discoloration, fracture or even loss. Our previous study showed implantation of autologous SHED could regenerate functional dental pulp. However, the detailed mechanism of the implanted SHED participating in dental pulp regeneration remains unknown. In this study, we implanted SHED in a porcine dental pulp regeneration model to evaluate the regenerative effect and identify whether SHED promoted angiogenesis in regenerated dental pulp. Firstly we verified that xenogenous SHED had the ability to regenerated pulp tissue of host in vivo. Then we found the vasculature in regenerated pulp originated from implanted SHED. In addition, stem cells were isolated from regenerated dental pulp, which exhibited good multi-differentiation properties and promoted angiogenesis in pulp regeneration process and these results demonstrated that SHED promoted angiogenesis in stem cell-mediated dental pulp regeneration.

PDLSCs Regulate Angiogenesis of Periodontal Ligaments via VEGF Transferred by Exosomes in Periodontitis.

Abnormal angiogenesis is one of the significant features in periodontitis leading to progressive inflammation, but angiogenic changes of periodontal ligaments under inflammatory condition were rarely reported. Periodontal ligament stem cells (PDLSCs) were a kind of dental stem cells associated with vascularization. Here we investigated the alteration of angiogenesis of periodontal ligament in periodontitis, and revealed an exosome-mediated pathway to support the effect of PDLSCs on angiogenic improvement. Vascular specific marker CD31 and VEGFA were found to be highly expressed in periodontal ligaments of periodontitis. The VEGFA expression was up-regulated in inflamed PDLSCs compared to control, meanwhile the tube formation of HUVECs was improved when co-cultured with inflamed PDLSCs. Exosomes secretion of PDSLCs was augmented by inflammation, and promoted angiogenesis of HUVECs, whereas blocking secretion of exosomes led to degenerated angiogenesis of HUVECs. Exosome-trasferred VEGFA was proven to be the crucial communicator between PDLSCs and HUVECs. Inflammation inhibited miR-17-5p expression of PDLSCs and relieved its target VEGFA. However, overexpression of miR-17-5p blocked the pro-angiogenic ability of inflamed PDLSCs. In conclusion, the findings indicated that vascularization of periodontal ligaments was enhanced, and inflammatory micro-environment of periodontitis facilitated pro-angiogenesis of PDLSCs through regulating exosome-mediated transfer of VEGFA, which was targeted by miR-17-5p.

Redundant let-7a suppresses the immunomodulatory properties of BMSCs by inhibiting the Fas/FasL system in osteoporosis.

Bone marrow-derived mesenchymal stem cell (BMSC) cytotherapy has emerged as a promising treatment strategy for refractory immune diseases; however, the influence of the pathologic conditions of donors on the immunomodulatory properties of BMSCs is still poorly understand. Here, we found that BMSCs that were derived from donors with osteoporosis were ineffective as cytotherapy for patients with experimental colitis and graft- vs.-host disease (GVHD). In vivo and in vitro assays revealed that the capacity of osteoporotic BMSCs to induce T-cell apoptosis declined as a result of decreased Fas and FasL protein. Additional analysis revealed that let-7a, a microRNA induced by TNF-α in osteoporosis, inhibited the expression of the Fas/FasL system via post-transcriptional regulation. By knocking down let-7a expression, we successfully recovered the immunosuppressive capacity of osteoporotic BMSCs and improved their therapy for experimental colitis and GVHD. Taken together, our study demonstrates that the immunomodulatory properties of BMSCs are suppressed in osteoporosis and illustrates the molecular mechanism that underlies this suppression. These findings might have important implications for the development of targeted strategies to improve BMSC cytotherapy.-Liao, L., Yu, Y., Shao, B., Su, X., Wang, H., Kuang, H., Jing, H., Shuai, Y., Yang, D., Jin, Y. Redundant let-7a suppresses the immunomodulatory properties of BMSCs by inhibiting the Fas/FasL system in osteoporosis.

Declining histone acetyltransferase GCN5 represses BMSC-mediated angiogenesis during osteoporosis.

Angiogenesis is disrupted in age-related and postmenopausal osteoporosis. However, the mechanisms of the disorder remain elusive. We confirmed in this study that, in accordance with the decrease of H-type vessels, the proangiogenic potential of bone marrow-derived mesenchymal stem cells (BMSCs) declined during osteoporosis. Screening of the histone acetyltransferase family revealed that GCN5 decreased in BMSCs derived from osteoporotic femur. Further analysis identified that GCN5 plays important roles in regulating the proangiogenic potential of BMSCs. GCN5 promoted BMSC-mediated angiogenesis by enhancing H3K9ac levels on the promoter of Vegf The decrease of GCN5 in osteoporotic BMSCs led to the decline of proangiogenic capacity. Accordingly, overexpression of GCN5 enhanced the proangiogenic potency of osteoporotic BMSCs. Furthermore, recovering GCN5 expression in vivo by lentiviral expression vector significantly attenuated the loss of angiogenesis in ovariectomized mouse femurs. Our study results revealed an epigenetic mechanism controlling BMSC-mediated angiogenesis and provided a novel therapeutic target for osteoporosis treatment.-Jing, H., Liao, L., Su, X., Shuai, Y. Zhang, X., Deng, Z., Jin, Y. Declining histone acetyltransferase GCN5 represses BMSC-mediated angiogenesis during osteoporosis.

Knockdown of MicroRNA Let-7a Improves the Functionality of Bone Marrow-Derived Mesenchymal Stem Cells in Immunotherapy.

Bone marrow-derived mesenchymal stem cells (MSCs) have been recently used in clinical treatment of inflammatory diseases. Practical strategies improving the immunosuppressive property of MSCs are urgently needed for MSC immunotherapy. In this study, we aimed to develop a microRNA-based strategy to improve MSC immunotherapy. Bioinformatic analysis revealed that let-7a targeted the 3' UTR of mRNA of Fas and FasL, both of which are essential for MSCs to induce T cell apoptosis. Knockdown of let-7a by specific inhibitor doubled Fas and Fas ligand (FasL) protein levels in MSCs. Because Fas attracts T cell migration and FasL induces T cell apoptosis, knockdown of let-7a significantly promoted MSC-induced T cell migration and apoptosis in vitro and in vivo. Importantly, MSCs knocked down of let-7a were more efficient to reduce the mortality, prevent the weight loss, suppress the inflammation reaction, and alleviate the tissue lesion of experimental colitis and graft-versus-host disease (GVHD) mouse models. In conclusion, knockdown of let-7a significantly improved the therapeutic effect of MSC cytotherapy on inflammatory bowel diseases and GVHD. With high safety and convenience, knockdown of let-7a is a potential strategy to improve MSC therapy for inflammatory diseases in clinic.

Circulating microRNA Panel as a Novel Biomarker to Diagnose Bisphosphonate-Related Osteonecrosis of the Jaw.

There is no defined biomarker for BRONJ diagnosis with satisfactory performance in clinic. In this study, we established the BRONJ model and selected 7 microRNAs as candidate for BRONJ diagnosis from microRNA microarray reported by other research. Dysregulated microRNAs during BRONJ were detected and validated in two independent animal experiments using serum samples. In the first part, serum miR-21, miR-23a and miR-145 were significantly altered in between BRONJ and control group. And an Indice was constructed as -0.032+(0.154×miR-21)+(0.145×miR-23a)+(-0.700×miR-145) using logistic regression model to improve diagnostic performance. The performance of Indice to differentiate BRONJ subjects from control group was analyzed as AUC of 0.82 (95% CI, 0.72-0.92) or 0.85 (95% CI, 0.73-0.97) in the first or second part. Moreover, the predictive performance of Indice to discriminate BRONJ-1w and BRONJ-4w from control group was displayed as AUC of 0.65 (95% CI, 0.47-0.84) or 0.75 (95% CI, 0.60-0.91), which was better than individual circulating microRNAs. In addition, the expressions of candidate microRNAs were validated in human samples. Consequently, we investigated a combined Indice constructed with circulating microRNAs for BRONJ diagnosis and prediction.

Dental Stem Cells and Tooth Regeneration.

Dental stem cells are a minor population of mesenchymal stem cells existing in specialized dental tissues, such as dental pulp, periodontium, apical papilla, dental follicle and so forth. Standard methods have been established to isolate and identify these stem cells. Due to their differentiation potential, these mesenchymal stem cells are promising for tooth repair. Dental stem cells have been emerging to regenerated teeth and periodontal tissues, ascribe to their self-renewal, multipotency and tissue specific differentiation potential. Therefore, dental stem cells based regeneration medicine highlights a promising access to repair damaged dental tissues or generate new teeth. In this review, we provide an overview of human dental stem cells including isolation and identification, involved pathways and outcomes of regenerative researches. A number of basic researches, preclinical studies and clinical trials have investigated that dental stem cells efficiently improve formation of dental specialized structure and healing of periodontal diseases, suggesting a great feasibility and prospect of these approaches in translational medicine of dental regeneration.

TNF-α Inhibits FoxO1 by Upregulating miR-705 to Aggravate Oxidative Damage in Bone Marrow-Derived Mesenchymal Stem Cells during Osteoporosis.

Decline of antioxidant defense after estrogen deficiency leads to oxidative damage in bone marrow-derived mesenchymal stem cells (BMMSCs), resulting a defect of bone formation in osteoporosis. Forkhead box O1 (FoxO1) protein is crucial for defending physiological oxidative damage in bone. But whether FoxO1 is involved in the oxidative damage during osteoporosis is largely unknown. In this study, we found that FoxO1 protein accumulation was decreased in BMMSCs of ovariectomized mice. The decrease of FoxO1 resulted in the suppression of manganese superoxide dismutase (Sod2) and catalase (Cat) expression and accumulation of reactive oxygen species (ROS), inhibiting the osteogenic differentiation of BMMSCs. The decline of FoxO1 protein was caused by tumor necrosis factor-alpha (TNF-α) accumulated after estrogen deficiency. Mechanistically, TNF-α activated NF-κB pathway to promote microRNA-705 expression, which function as a repressor of FoxO1 through post-transcriptional regulation. Inhibition of NF-κB pathway or knockdown of miR-705 largely prevented the decline of FoxO1-mediated antioxidant defense caused by TNF-α and ameliorated the oxidative damage in osteoporotic BMMSCs. Moreover, the accumulated ROS further activated NF-κB pathway with TNF-α, which formed a feed-forward loop to persistently inhibiting FoxO1 protein accumulation in BMMSCs. In conclusion, our study revealed that the decline of FoxO1 is an important etiology factor of osteoporosis and unclosed a novel mechanism of FoxO1 regulation by TNF-α. These findings suggested a close correlation between inflammation and oxidative stress in stem cell dysfunction during degenerative bone diseases.

Suppression of EZH2 Prevents the Shift of Osteoporotic MSC Fate to Adipocyte and Enhances Bone Formation During Osteoporosis.

During osteoporosis, the shift of mesenchymal stem cell (MSC) lineage commitment to adipocyte leads to the imbalance between bone mass and fat, which increases the risk of fracture. The Enhancer of Zeste homology 2 (EZH2), which methylates histone H3 on lysine 27 (H3K27me3), controls MSC cell lineage commitment. However, whether EZH2 is related to osteoporosis remains elusive. In our study, we found EZH2 expression was significantly increased in osteoporotic MSCs. EZH2 directly increased H3K27me3 levels on promoters of Wnt1, Wnt6, and Wnt10a to silence Wnt gene transcription. The inhibition of Wnt/ß-catenin signaling shifted MSC cell lineage commitment to adipocyte. Knockdown of EZH2 by lentivirus-expressing shRNA rescued the abnormal fate of osteoporotic MSC. By employing the H3K27me3 inhibitor DZNep, we effectively derepressed Wnt signaling and improved osteogenic differentiation of osteoporotic MSCs in vitro. Furthermore, in vivo administration of DZNep successfully increased bone formation and repressed excessive bone marrow fat formation in osteoporotic mice. Noteworthy, DZNep treatment persistently enhanced osteogenic differentiation of endogenous MSCs. In conclusion, our study demonstrated that redundant EZH2 shifted MSC cell lineage commitment to adipocyte, which contributed to the development of osteoporosis. We also provided EZH2 as a novel therapeutic target for improving bone formation during osteoporosis.

Estrogen preserves Fas ligand levels by inhibiting microRNA-181a in bone marrow-derived mesenchymal stem cells to maintain bone remodeling balance.

Estrogen protects bone loss by promoting Fas ligand (FasL) transcription in osteoclasts and osteoblasts to induce apoptosis of osteoclasts. Bone marrow-derived mesenchymal stem cells (BMMSCs) express FasL protein, which is necessary for BMMSCs to induce T-cell apoptosis in cell therapy. However, the physiologic function of FasL in BMMSCs is unknown. In this study, using an in vitro coculture system and an in vivo BMMSC transplantation assay, we found that BMMSCs potently induced apoptosis of osteoclasts through the FasL/Fas pathway. Estrogen was necessary for this process as a promoter of FasL protein accumulation in BMMSCs. Furthermore, estrogen elevated FasL protein accumulation, not by increasing FasL gene transcription, but through microRNA-mediated posttranscriptional regulation. In brief, estrogen down-regulated expression of miR-181a, a negative modulator of FasL targeting the 3'-UTR of FasL mRNA. Estrogen deficiency resulted in excessive miR-181a, which decreased FasL protein levels to suppress BMMSC-induced osteoclast apoptosis. Furthermore, knockdown of miR-181a recovered the BMMSC defect to induce osteoclast apoptosis during estrogen deficiency. Taken together, our results showed that estrogen preserves FasL protein accumulation by inhibiting miR-181a expression in BMMSCs to maintain bone remodeling balance, suggesting a novel mechanism by which estrogen preserves bone mass.