An anti-inflammatory active ingredients in Poriae cutis: Screening based on network pharmacology.

Hyperuricemia (HUA) is a disorder of uric acid metabolism, which can lead to the formation of gouty arthritis, kidney inflammation and other damages. Previous studies have found that the alcohol extract of Poria cutis can reduce the level of uric acid and protect against kidney injury. Based on network pharmacology, the core targets and main active components of P. cutis intervention in HUA were determined. Most of the potential active ingredients are triterpenoid acids such as tumulosic acid (TA) and eburicoic acid (EA), and the potential targets are TNF and IL-6, which are associated with inflammation. In vitro experiments have shown that TA can significantly inhibit the release of NO, TNF-α and IL-6 in inflammatory RAW264.7 cell culture medium and the expression of TNF-α and IL-6 in RAW264.7 cells. This study suggests that TA based on network pharmacological screening has obvious anti-inflammatory effect on inflammatory RAW264.7 cells and is a promising anti-inflammatory compound.

Aerogels for Thermal Protection and Their Application in Aerospace.

With the continuous development of the world's aerospace industry, countries have put forward higher requirements for thermal protection materials for aerospace vehicles. As a nano porous material with ultra-low thermal conductivity, aerogel has attracted more and more attention in the thermal insulation application of aerospace vehicles. At present, the summary of aerogel used in aerospace thermal protection applications is not comprehensive. Therefore, this paper summarizes the research status of various types of aerogels for thermal protection (oxide aerogels, organic aerogels, etc.), summarizes the hot issues in the current research of various types of aerogels for thermal protection, and puts forward suggestions for the future development of various aerogels. For oxide aerogels, it is necessary to further increase their use temperature and inhibit the sintering of high-temperature resistant components. For organic aerogels, it is necessary to focus on improving the anti-ablation, thermal insulation, and mechanical properties in long-term aerobic high-temperature environments, and on this basis, find cheap raw materials to reduce costs. For carbon aerogels, it is necessary to further explore the balanced relationship between oxidation resistance, mechanics, and thermal insulation properties of materials. The purpose of this paper is to provide a reference for the further development of more efficient and reliable aerogel materials for aerospace applications in the future.

Inhibition of miR338 rescues cleidocranial dysplasia in Runx2 mutant mice partially via the Hif1a-Vegfa axis.

Haploinsufficiency of Runt-related transcription factor-2 (RUNX2) is responsible for cleidocranial dysplasia (CCD), a rare hereditary disease with a range of defects, including delayed closure of the cranial sutures and short stature. Symptom-based treatments, such as a combined surgical-orthodontic approach, are commonly used to treat CCD patients. However, there have been few reports of treatments based on Runx2-specific regulation targeting dwarfism symptoms. Previously, we found that the miR338 cluster, a potential diagnostic and therapeutic target for postmenopausal osteoporosis, could directly target Runx2 during osteoblast differentiation in vitro. Here, we generated miR338-/-;Runx2+/- mice to investigate whether inhibition of miR338 could rescue CCD defects caused by Runx2 mutation in vivo. We found that the dwarfism phenotype caused by Runx2 haploinsufficiency was recovered in miR338-/-;Runx2+/- mice, with complete bone density restoration and quicker closure of fontanels. Single-cell RNA-seq analysis revealed that knockout of miR338 specifically rescued the osteoblast lineage priming ability of bone marrow stromal cells in Runx2+/- femurs, which was further confirmed by Osterix-specific conditional knockout of miR338 in Runx2+/- mice (OsxCre; miR338 fl/fl;Runx2+/-). Mechanistically, ablation of the miR338 cluster in Runx2+/- femurs directly rescued the Hif1a-Vegfa pathway in Runx2+/- osteoblasts, as proven by gene expression profiles and ChIP and Re-ChIP assays. Collectively, our data revealed the genetic interaction between Runx2 and the miR338 cluster during osteoblast differentiation and implied that the miR338 cluster could be a potential therapeutic target for CCD.

Changes in paediatric dental clinic after reopening during COVID-19 pandemic in Wuhan: a retrospective study.

OBJECTIVES: Affected by COVID-19 pandemic, The Department of Paediatric Dentistry of School and Hospital of Stomatology, Wuhan University was closed in late January 2020, and resumed on 20 April. Our study aimed to explore the effects of COVID-19 pandemic on paediatric dental services which might assist global paediatric dentists to build confidence and make appropriate policies under the pandemic. DESIGN: A retrospective study was performed. Medical records of patients were retrieved but without any private information, including patient name, ID number and address. PARTICIPANTS: All data of the patients from 20 April to 31 July in 2020 and 2019 were extracted and analysed including demographics, dental diagnosis and treatment methods. A total of 18 198 patients were included in the study. RESULTS: During this period, no medical staff or patient was infected with COVID-19 due to dental services. A total of 6485 in 2020 but 11 713 during the same period in 2019 visited the department. Compared with 2019, gender distribution did not change, but age distribution changed with an increase under 6-year-old. The diagnoses including caries, retained primary teeth, malocclusion, deep pits and fissures changed significantly, while pulpitis, apical periodontitis, tooth trauma, early loss of primary teeth, supernumerary teeth showed little change. Aerosol generating procedures were adopted less frequently overall in this period. CONCLUSIONS: The reopening of paediatric dental services is proceeding steadily with significant changes in the characteristics of the patients and treatment procedures.

Biomimetic remineralization of artificial caries dentin lesion using Ca/P-PILP.

OBJECTIVE: To assess the ultrastructural change of demineralized dentin collagen during calcium phosphate polymer-induced liquid precursor (Ca/P-PILP) mediated remineralization process and to evaluate the biomimetic remineralization potential of high concentration Ca/P-PILP at demineralized artificial caries dentin lesion, additionally to investigate the bond interfacial integrity as well as the bonding strength of the biomimetic remineralized artificial caries dentin lesion. METHODS: Demineralized dentin collagen of 5 µm thick was biomimetically remineralized with low, medium concentration Ca/P-PILP for 10 days and high concentration Ca/P-PILP for 10, 15, 20 days. Artificial caries dentin lesion at a thickness of 150 ± 50 µm was biomimetically remineralized with high concentration Ca/P-PILP for 20 days. The biomimetic remineralization of demineralized dentin collagen was observed by scanning electron microscopy (SEM). The biomimetic remineralization intensity and depth of artificial caries dentin lesion was assessed by Electron Probe Micro Analyzer (EPMA). The bonding interfacial integrity between remineralized artificial caries dentin and composite resin was observed by Swept-source optical coherence tomography (SS-OCT) and the bonding strength of remineralized artificial caries dentin was evaluated by micro-tensile bond strength analysis (µTBS). RESULTS: Solely PAA-PASP solution and solely saturated Ca/P solution can't achieve dentin collagen remineralization. Increased concentration of Ca/P-PILP and prolonged remineralization time can enhance the biomimetic remineralization intensity of demineralized dentin collagen. After treating with high concentration Ca/P-PILP, a 150 ± 50 µm thick layer of demineralized artificial caries dentin lesion was not fully remineralized, and the biomimetic remineralization intensity reached up to 88.0%. Furthermore, a better bonding interfacial integrity with less microgap and increased bond strength at both baseline level and aging level were observed when artificial caries dentin lesion was biomimetically remineralized with high concentration Ca/P-PILP. SIGNIFICANCE: Biomimetic remineralization of demineralized caries dentin lesion promotes its clinical properties for resin composited adhesive restoration.

Circulating miR-338 Cluster activities on osteoblast differentiation: Potential Diagnostic and Therapeutic Targets for Postmenopausal Osteoporosis.

MicroRNAs (miRNAs) are the most abundant RNA species found in serum, and recently, several miRNAs have been found to be associated with osteoporosis. However, the development of such associated miRNAs into diagnostic and therapeutic targets remains unaddressed, mostly because of a lack of functional validation. Here, we identified circulating miR-338 associated with postmenopausal osteoporosis, and performed functional validation in vivo and in vitro. Methods: We collected the serum from postmenopausal osteoporosis patients (N=15) and female volunteers of the same age but with normal bone density (N=15) and examined the enrichment of miR-338 cluster. We also confirmed such enrichment using mice subjected to ovariectomy at different stages. We employed primary bone marrow stromal cells from mice and the MC-3T3 cell line along with CRISPR, RNA-seq and ChIP-qPCR to validate the biological function of secreted miR-338 cluster on osteoblastic differentiation and their upstream regulators. Moreover, we generated miR-338 knockout mice and OVX mice injected with an inhibitor against miR-338 cluster to confirm its biological function in vivo. Results: We observed a significant enrichment of miR-338 cluster in postmenopausal osteoporosis patients. Such enrichment was also prominent in serum from mice subjected to ovariectomy and was detected much earlier than bone density decreases revealed by micro-CT. We also confirmed the presence of an estrogen-dependent Runx2/Sox4/miR-338 positive feedback loop that modulated osteoblast differentiation, providing a possible explanation for our clinical findings. Moreover, deletion of the miR-338 cluster or direct intravenous injection of an miR-338 cluster inhibitor significantly prevented osteoporosis after ovariectomy. Conclusion: Circulating miR-338 cluster in the serum could serve as a promising diagnostic and therapeutic target for postmenopausal osteoporosis patients.

Effect of Liquid Platelet-rich Fibrin and Platelet-rich Plasma on the Regenerative Potential of Dental Pulp Cells Cultured under Inflammatory Conditions: A Comparative Analysis.

INTRODUCTION: Platelet-rich plasma (PRP) has been widely used in regenerative dentistry for over 2 decades. Nevertheless, previous studies have shown that its growth factor content is released over a short time period, and the application of anticoagulants limits its regenerative potential. Therefore, a second-generation platelet concentrate (liquid platelet-rich fibrin [PRF]) was developed without the use of anticoagulants and with shorter centrifugation times. The purpose of the present study was to compare the cellular regenerative activity of human dental pulp cells (hDPCs) when cultured with either liquid PRF or traditional PRP. METHODS: The regenerative potential of hDPCs isolated from healthy human third molars (18-22 years, n = 5) was investigated in both normal and inflammatorylike conditions (lipopolysaccharide [LPS]) and assessed for their potential for dentin repair. The effects of liquid PRF and PRP were assessed for cellular migration, proliferation, and odontoblastic differentiation using a transwell assay, scratch assay, proliferation assay, alkaline phosphatase assay, alizarin red staining, and real-time polymerase chain reaction for genes encoding collagen type 1 alpha 1, dentin sialophosphoprotein, and dentin matrix protein 1, respectively. The effects of both platelet concentrates were also assessed for their ability to influence nuclear translocation of nuclear factor kappa B (p65) by immunofluorescence, and reverse-transcription polymerase chain reaction for genes encoding interleukin-1ß, tumor necrosis factor alpha, and nuclear factor kappa B (p65) during an inflammatory condition. RESULTS: Both PRP and liquid PRF increased the migration and proliferation of hDPCs when compared with the control group, whereas liquid PRF showed a notable significant increase in migration when compared with PRP. Furthermore, liquid PRF induced significantly greater alkaline phosphatase activity, alizarin red staining, and a messenger RNA expression of genes encoding collagen type 1 alpha 1, dentin sialophosphoprotein, and dentin matrix protein 1 when compared with PRP. When hDPCs were cultured with LPS to stimulate an inflammatory environment, a marked decrease in dentin-related repair was observed. When liquid PRF was cultured within this inflammatory environment, the reduced regenerative potential in this LPS-produced environment was significantly and markedly improved, facilitating hDPC regeneration. The messenger RNA expression of inflammatory markers including tumor necrosis factor alpha, interleukin-1ß, and p65 were all significantly decreased in the presence of liquid PRF, and, furthermore, liquid PRF also inhibited the transport of p65 to the nucleus in hDPCs (suggesting a reduced inflammatory condition). CONCLUSIONS: The findings from the present study suggest that liquid PRF promoted greater regeneration potential of hDPCs when compared with traditional PRP. Furthermore, liquid PRF also attenuated the inflammatory condition created by LPS and maintained a supportive regenerative ability for the stimulation of odontoblastic differentiation and reparative dentin in hDPCs.

Effects of concentrated growth factor on proliferation, migration, and differentiation of human dental pulp stem cells in vitro.

Concentrated growth factor, a novel autologous plasma extract, contained various growth factors which promoted tissue regeneration. In this study, we aimed to investigate the biological effects of concentrated growth factor on human dental pulp stem cells. The microstructure and biocompatibility of concentrated growth factor scaffolds were evaluated by scanning electron microscopy. Cell proliferation and migration, odontoblastic and endothelial cell differentiation potential were assessed after exposing dental pulp stem cells to different concentrations (5%, 10%, 20%, 50%, or 80%) of concentrated growth factor extracts. The results revealed that concentrated growth factor scaffolds possessed porous fibrin network with platelets and leukocytes, and showed great biocompatibility with dental pulp stem cells. Higher cell proliferation rates were detected in the concentrated growth factor-treated groups in a dose-dependent manner. Interestingly, in comparison to the controls, the low doses (<50%) of concentrated growth factor increased cell migration, alkaline phosphatase activity, and mineralized tissue deposition, while the cells treated in high doses (50% or 80%) showed no significant difference. After stimulating cell differentiation, the expression levels of dentin matrix protein-1, dentin sialophosphoprotein, vascular endothelial growth factor receptor-2 and cluster of differentiation 31 were significantly upregulated in concentrated growth factor-supplemented groups than those of the controls. Furthermore, the dental pulp stem cell-derived endothelial cells co-induced by 5% concentrated growth factor and vascular endothelial growth factor formed the most amount of mature tube-like structures on Matrigel among all groups, but the high-dosage concentrated growth factor exhibited no or inhibitory effect on cell differentiation. In general, our findings confirmed that concentrated growth factor promoted cell proliferation, migration, and the dental pulp stem cell-mediated dentinogenesis and angiogenesis process, by which it might act as a growth factor-loaded scaffold to facilitate dentin-pulp complex healing.