Professional psychological qualities of Chinese medical students: theoretical models, questionnaire development, and relationship with mental health.

Introduction: Professional psychological qualities are crucial for individuals' career development and overall well-being, especially in clinical medical professions. Medical students often face significant work, academic, and doctor-patient communication pressures, which can challenge their mental and emotional health. Measuring and understanding the relationship between medical students' professional psychological qualities and their mental health is of significant practical importance. Methods: This study developed a comprehensive professional psychological qualities scale through a series of qualitative and quantitative studies, consisting of three main components and thirteen secondary dimensions. The scale's reliability was assessed using Cronbach's α coefficients. In Study 2, the scale was administered to 972 medical students to explore their anxiety and depression levels. A simple mediation analysis was conducted to investigate the relationship between professional psychological qualities, anxiety, and depression. Results: The professional psychological qualities scale demonstrated satisfactory reliability, with a total scale α coefficient of 0.947 and subscale α coefficients ranging from 0.895 to 0.933. The mediation analysis revealed that medical students' professional psychological qualities directly negatively impact depression levels and indirectly positively influence them via their effects on anxiety levels, exhibiting an overall masking effect unrelated to depression levels. Discussion: This study addresses the gap in research on the professional psychological qualities of medical students by providing a reliable measurement tool. The findings shed light on the complex mechanisms through which these qualities impact the mental health process. The scale can be used by other researchers to assess medical students' professional psychological qualities and further investigate their relationship with mental health outcomes.

ROS in diabetic atria regulate SK2 degradation by Atrogin-1 through the NF-κB signaling pathway.

One of the independent risk factors for atrial fibrillation is diabetes mellitus (DM); however, the underlying mechanisms causing atrial fibrillation in DM are unknown. The underlying mechanism of Atrogin-1-mediated SK2 degradation and associated signaling pathways are unclear. The aim of this study was to elucidate the relationship among reactive oxygen species (ROS), the NF-κB signaling pathway, and Atrogin-1 protein expression in the atrial myocardia of DM mice. We found that SK2 expression was downregulated comitant with increased ROS generation and enhanced NF-κB signaling activation in the atrial cardiomyocytes of DM mice. These observations were mimicked by exogenously applicating H2O2 and by high glucose culture conditions in HL-1 cells. Inhibition of ROS production by diphenyleneiodonium chloride or silencing of NF-κB by siRNA decreased the protein expression of NF-κB and Atrogin-1 and increased that of SK2 in HL-1 cells with high glucose culture. Moreover, chromatin immunoprecipitation assay demonstrated that NF-κB/p65 directly binds to the promoter of the FBXO32 gene (encoding Atrogin-1), regulating the FBXO32 transcription. Finally, we evaluated the therapeutic effects of curcumin, known as a NF-κB inhibitor, on Atrogin-1 and SK2 expression in DM mice and confirmed that oral administration of curcumin for 4 weeks significantly suppressed Atrogin-1 expression and protected SK2 expression against hyperglycemia. In summary, the results from this study indicated that the ROS/NF-κB signaling pathway participates in Atrogin-1-mediated SK2 regulation in the atria of streptozotocin-induced DM mice.

Adipose-derived mesenchymal stem cells (MSCs) are a superior cell source for bone tissue engineering.

Effective bone regeneration through tissue engineering requires a combination of osteogenic progenitors, osteoinductive biofactors and biocompatible scaffold materials. Mesenchymal stem cells (MSCs) represent the most promising seed cells for bone tissue engineering. As multipotent stem cells that can self-renew and differentiate into multiple lineages including bone and fat, MSCs can be isolated from numerous tissues and exhibit varied differentiation potential. To identify an optimal progenitor cell source for bone tissue engineering, we analyzed the proliferative activity and osteogenic potential of four commonly-used mouse MSC sources, including immortalized mouse embryonic fibroblasts (iMEF), immortalized mouse bone marrow stromal stem cells (imBMSC), immortalized mouse calvarial mesenchymal progenitors (iCAL), and immortalized mouse adipose-derived mesenchymal stem cells (iMAD). We found that iMAD exhibited highest osteogenic and adipogenic capabilities upon BMP9 stimulation in vitro, whereas iMAD and iCAL exhibited highest osteogenic capability in BMP9-induced ectopic osteogenesis and critical-sized calvarial defect repair. Transcriptomic analysis revealed that, while each MSC line regulated a distinct set of target genes upon BMP9 stimulation, all MSC lines underwent osteogenic differentiation by regulating osteogenesis-related signaling including Wnt, TGF-ß, PI3K/AKT, MAPK, Hippo and JAK-STAT pathways. Collectively, our results demonstrate that adipose-derived MSCs represent optimal progenitor sources for cell-based bone tissue engineering.

Single-Cell RNA-Seq Analysis Identifies Angiotensinogen and Galanin as Unique Molecular Markers of Acinar Cells in Murine Salivary Glands.

The submandibular gland (SMG) and sublingual gland (SLG) are two of three major salivary glands in mammals and comprise serous and mucous acinar cells. The two glands share some functional properties, which are largely dependent on the types of acinar cells. In recent years, while ScRNA-seq (single-cell sequencing) with a 10 × platform has been used to explore molecular markers in salivary glands, few studies have examined the acinar heterogeneity and unique molecular markers between SMG and SLG. This study aimed to identify the molecular markers of acinar cells in the SLG and SMG. We performed ScRNA-seq analyses in 4-week-old mice and verified the screened molecular markers using reverse transcription-quantitative real-time PCR, immunohistochemistry, and immunofluorescence. Our results showed prominently heterogeneous acinar cells, although there was great similarity in the cluster composition between the two glands at 4 weeks. Furthermore, we demonstrated that Agt is a specific marker of SMG serous acinar cells, whereas Gal is a specific marker of SLG mucous acinar cells. Trajectory inference revealed that Agt and Gal represent two types of differential acinar cell clusters during late development in adults. Thus, we reveal previously unknown specific markers for salivary acinar cell diversity, which has extensive implications for their further functional research.

Establishing and characterizing human stem cells from the apical papilla immortalized by hTERT gene transfer.

Stem cells from the apical papilla (SCAPs) are promising candidates for regenerative endodontic treatment and tissue regeneration in general. However, harvesting enough cells from the limited apical papilla tissue is difficult, and the cells lose their primary phenotype over many passages. To get over these challenges, we immortalized human SCAPs with lentiviruses overexpressing human telomerase reverse transcriptase (hTERT). Human immortalized SCAPs (hiSCAPs) exhibited long-term proliferative activity without tumorigenic potential. Cells also expressed mesenchymal and progenitor biomarkers and exhibited multiple differentiation potentials. Interestingly, hiSCAPs gained a stronger potential for osteogenic differentiation than the primary cells. To further investigate whether hiSCAPs could become prospective seed cells in bone tissue engineering, in vitro and in vivo studies were performed, and the results indicated that hiSCAPs exhibited strong osteogenic differentiation ability after infection with recombinant adenoviruses expressing BMP9 (AdBMP9). In addition, we revealed that BMP9 could upregulate ALK1 and BMPRII, leading to an increase in phosphorylated Smad1 to induce the osteogenic differentiation of hiSCAPs. These results support the application of hiSCAPs in tissue engineering/regeneration schemes as a stable stem cell source for osteogenic differentiation and biomineralization, which could be further used in stem cell-based clinical therapies.

Corrigendum to "Establishment and functional characterization of the reversibly immortalized mouse glomerular podocytes (imPODs)" [Genes & Diseases 5 (2018) 137-149].

[This corrects the article DOI: 10.1016/j.gendis.2018.04.003.].

Corrigendum to "The development of a sensitive fluorescent protein-based transcript reporter for high throughput screening of negative modulators of lncRNAs" [Genes & Diseases 5 (2018) 62-74].

[This corrects the article DOI: 10.1016/j.gendis.2018.02.001.].

Corrigendum to "Characterization of the essential role of bone morphogenetic protein 9 (BMP9) in osteogenic differentiation of mesenchymal stem cells (MSCs) through RNA interference" [Genes & Diseases 5(2018):172-184].

[This corrects the article DOI: 10.1016/j.gendis.2018.04.006.].

Upregulated lncRNA NORAD can diagnose acute cerebral ischemic stroke patients and predict poor prognosis.

INTRODUCTION: Acute cerebral ischemic stroke (AIS) dramatically influences patients' quality of life. lncRNA NORAD (NORAD) has been studied in cerebrovascular diseases, which are potential risk factors for AIS. The specific significance of NORAD is unclear. This study aimed to assess the role of NORAD in AIS, and to provide therapeutic value for its' treatment. MATERIAL AND METHODS: A total of 103 AIS patients and 95 healthy individuals (control) were enrolled into this study. Expression level of NORAD in the plasma of all participants was analyzed by PCR. Diagnostic potential of NORAD in AIS was evaluated by ROC analysis, while Kaplan-Meier and Cox regression analyses were conducted to assess its' prognostic value in AIS. RESULTS: A significantly increased level of NORAD was observed in AIS patients compared with healthy individuals. The upregulation of NORAD could dramatically discriminate AIS patients from healthy individuals with high sensitivity (81.60%) and specificity (88.40%). NORAD was positively correlated with patients' high-sensitivity C-reactive protein (hs CRP, r = 0.796), matrix metalloproteinase-9 (MMP9, r = 0.757), and NIHSS scores ( r = 0.840), and negatively related to pc-ASPECTS scores ( r = -0.607). Moreover, NORAD upregulation was associated with patients' unfavorable prognosis and served as an independent prognostic biomarker, together with NIHSS and pc-ASPECTS scores of AIS patients. CONCLUSIONS: NORAD was upregulated in AIS, which can discriminate AIS patients, and was closely correlated with severe development and poor prognosis of patients.

Effectiveness of biomechanically stable pergola-like additively manufactured scaffold for extraskeletal vertical bone augmentation.

Objective: Extraskeletal vertical bone augmentation in oral implant surgery requires extraosseous regeneration beyond the anatomical contour of the alveolar bone. It is necessary to find a better technical/clinical solution to solve the dilemma of vertical bone augmentation. 3D-printed scaffolds are all oriented to general bone defect repair, but special bone augmentation design still needs improvement. Methods: This study aimed to develop a structural pergola-like scaffold to be loaded with stem cells from the apical papilla (SCAPs), bone morphogenetic protein 9 (BMP9) and vascular endothelial growth factor (VEGF) to verify its bone augmentation ability even under insufficient blood flow supply. Scaffold biomechanical and fluid flow optimization design by finite element analysis (FEA) and computational fluid dynamics (CFD) was performed on pergola-like additive-manufactured scaffolds with various porosity and pore size distributions. The scaffold geometrical configuration showing better biomechanical and fluid dynamics properties was chosen to co-culture for 2 months in subcutaneously into nude mice, with different SCAPs, BMP9, and (or) VEGF combinations. Finally, the samples were removed for Micro-CT and histological analysis. Results: Micro-CT and histological analysis of the explanted scaffolds showed new bone formation in the "Scaffold + SCAPs + BMP9" and the "Scaffold + SCAPs + BMP9 + VEGF" groups where the VEGF addition did not significantly improve osteogenesis. No new bone formation was observed either for the "Blank Scaffold" and the "Scaffold + SCAPs + GFP" group. The results of this study indicate that BMP9 can effectively promote the osteogenic differentiation of SCAPs. Conclusion: The pergola-like scaffold can be used as an effective carrier and support device for new bone regeneration and mineralization in bone tissue engineering, and can play a crucial role in obtaining considerable vertical bone augmentation even under poor blood supply.

Efficient bone regeneration of BMP9-stimulated human periodontal ligament stem cells (hPDLSCs) in decellularized bone matrix (DBM) constructs to model maxillofacial intrabony defect repair.

BACKGROUND: BMP9-stimulated DPSCs, SCAPs and PDLSCs are effective candidates for repairing maxillofacial bone defects in tissue engineering, while the most suitable seed cell source among these three hDMSCs and the optimal combination of most suitable type of hDMSCs and BMP9 have rarely been explored. Moreover, the orthotopic maxillofacial bone defect model should be valuable but laborious and time-consuming to evaluate various candidates for bone regeneration. Thus, inspired from the maxillofacial bone defects and the traditional in vivo ectopic systems, we developed an intrabony defect repair model to recapitulate the healing events of orthotopic maxillofacial bone defect repair and further explore the optimized combinations of most suitable hDMSCs and BMP9 for bone defect repair based on this modified ectopic system. METHODS: Intrabony defect repair model was developed by using decellularized bone matrix (DBM) constructs prepared from the cancellous part of porcine lumbar vertebral body. We implanted DBM constructs subcutaneously on the flank of each male NU/NU athymic nude mouse, followed by directly injecting the cell suspension of different combinations of hDMSCs and BMP9 into the central hollow area of the constructs 7 days later. Then, the quality of the bony mass, including bone volume fraction (BV/TV), radiographic density (in Hounsfield units (HU)) and the height of newly formed bone, was measured by micro-CT. Furthermore, the H&E staining and immunohistochemical staining were performed to exam new bone and new blood vessel formation in DBM constructs. RESULTS: BMP9-stimulated periodontal ligament stem cells (PDLSCs) exhibited the most effective bone regeneration among the three types of hDMSCs in DBM constructs. Furthermore, an optimal dose of PDLSCs with a specific extent of BMP9 stimulation was confirmed for efficacious new bone and new blood vessel formation in DBM constructs. CONCLUSIONS: The reported intrabony defect repair model can be used to identify optimized combinations of suitable seed cells and biological factors for bone defect repair and subsequent development of efficacious bone tissue engineering therapies.

Validation of superior reference genes in mouse submandibular glands under developmental and functional regeneration states.

Saliva is crucial for lubricating the mouth and aiding in food digestion. However, the occurrence of oral dysfunction, such as xerostomia, dysphagia or oral infection can markedly reduce the quality of life of affected individuals. The major salivary glands include the submandibular gland (SMG), and sublingual and parotid glands; they are the larger glands in mammals that produce the majority of the saliva. The SMG serves as an effective model for the study of branching morphogenesis and functional regeneration. In order to better understand the key dynamic gene expression patterns during salivary gland development and functional regeneration, it is crucial to search for a panel of reliable reference genes. The present study thus aimed to identify superior reference genes to normalize gene expression data in the SMG under states of development and functional regeneration. First, the developmental SMG samples were harvested from mice in the embryonic and post­natal periods. Functional regeneration samples from a ductal ligation/de­ligation model were obtained at several stages. A total of 12 reference genes (Actb, Actg1, Ubc, Uba1, Uba52, Ube2c, Tuba1a, Tuba1b, Tubb5, H2afy, H2afx and Gapdh) from 430 candidates involving tubulin, histone, actin, ubiquitin and GAPDH family members were screened via transcriptome sequencing (RNA­seq) analysis. RT­qPCR (SYBR­Green) and western blot analysis were then used to semi­quantitatively assess gene and protein expression. The stability of expression was evaluated using the ΔCq, geNorm, BestKeeper, NormFinder and RefFinder methods and software. Actg1 exhibited the highest stability in the SMG developmental stage, while Tubb5 was recommended as the most stable reference gene for the SMG regenerative stage. In summary, the present study provides evidence­based selections for superior reference genes in the SMG during the stages of development and functional regeneration.

Modeling lung diseases using reversibly immortalized mouse pulmonary alveolar type 2 cells (imPAC2).

BACKGROUND: A healthy alveolar epithelium is critical to the gas exchange function of the lungs. As the major cell type of alveolar epithelium, alveolar type 2 (AT2) cells play a critical role in maintaining pulmonary homeostasis by serving as alveolar progenitors during lung injury, inflammation, and repair. Dysregulation of AT2 cells may lead to the development of acute and chronic lung diseases and cancer. The lack of clinically relevant AT2 cell models hampers our ability to understand pulmonary diseases. Here, we sought to establish reversibly immortalized mouse pulmonary alveolar type 2 cells (imPAC2) and investigate their potential in forming alveolar organoids to model pulmonary diseases. METHODS: Primary mouse pulmonary alveolar cells (mPACs) were isolated and immortalized with a retroviral expression of SV40 Large T antigen (LTA). Cell proliferation and survival was assessed by crystal violet staining and WST-1 assays. Marker gene expression was assessed by qPCR, Western blotting, and/or immunostaining. Alveolar organoids were generated by using matrigel. Ad-TGF-ß1 was used to transiently express TGF-ß1. Stable silencing ß-catenin or overexpression of mutant KRAS and TP53 was accomplished by using retroviral vectors. Subcutaneous cell implantations were carried out in athymic nude mice. The retrieved tissue masses were subjected to H & E histologic evaluation. RESULTS: We immortalized primary mPACs with SV40 LTA to yield the imPACs that were non-tumorigenic and maintained long-term proliferative activity that was reversible by FLP-mediated removal of SV40 LTA. The EpCAM+ AT2-enriched subpopulation (i.e., imPAC2) was sorted out from the imPACs, and was shown to express AT2 markers and form alveolar organoids. Functionally, silencing ß-catenin decreased the expression of AT2 markers in imPAC2 cells, while TGF-ß1 induced fibrosis-like response by regulating the expression of epithelial-mesenchymal transition markers in the imPAC2 cells. Lastly, concurrent expression of oncogenic KRAS and mutant TP53 rendered the imPAC2 cells a tumor-like phenotype and activated lung cancer-associated pathways. Collectively, our results suggest that the imPAC2 cells may faithfully represent AT2 populations that can be further explored to model pulmonary diseases.

Flavonoid Baicalein Suppresses Oral Biofilms and Protects Enamel Hardness to Combat Dental Caries.

The objectives of this study were to investigate the effects of a novel method using flavonoids to inhibit Streptococcus mutans (S. mutans), Candida albicans (C. albicans) and dual-species biofilms and to protect enamel hardness in a biofilm-based caries model for the first time. Several flavonoids, including baicalein, naringenin and catechin, were tested. Gold-standard chlorhexidine (CHX) and untreated (UC) groups served as controls. Optimal concentrations were determined by cytotoxicity assay. Biofilm MTT, colony-forming-units (CFUs), biofilm biomass, lactic acid and polysaccharide production were evaluated. Real-time-polymerase-chain reaction (qRT-PCR) was used to determine gene expressions in biofilms. Demineralization of human enamel was induced via S. mutans-C. albicans biofilms, and enamel hardness was measured. Compared to CHX and UC groups, the baicalein group achieved the greatest reduction in S. mutans, C. albicans and S. mutans-C. albicans biofilms, yielding the least metabolic activity, polysaccharide synthesis and lactic acid production (p < 0.05). The biofilm CFU was decreased in baicalein group by 5 logs, 4 logs, 5 logs, for S. mutans, C. albicans and S. mutans-C. albicans biofilms, respectively, compared to UC group. When tested in a S. mutans-C. albicans in vitro caries model, the baicalein group substantially reduced enamel demineralization under biofilms, yielding an enamel hardness that was 2.75 times greater than that of UC group. Hence, the novel baicalein method is promising to inhibit dental caries by reducing biofilm formation and protecting enamel hardness.

Reversely immortalized mouse salivary gland cells presented a promising metabolic and fibrotic response upon BMP9/Gdf2 stimulation.

The submandibular gland (SMG) and the sublingual gland (SLG) are two of the three major salivary glands in mammals. In mice, they are adjacent to each other and open into the oral cavity, producing saliva to lubricate the mouth and aid in food digestion. Though salivary gland dysfunction accompanied with fibrosis and metabolic disturbance is common in clinic, in-depth mechanistic research is lacking. Currently, research on how to rescue salivary function is challenging, as it must resort to using terminally differentiated acinar cells or precursor acinar cells with unknown differentiation. In this study, we established reversely immortalized mouse primary SMG cells (iSMGCs) and SLG cells (iSLGCs) on the first postnatal day (P0). The iSMGCs and iSLGCs grew well, exhibited many salivary gland characteristics, and retained the metabolism-related genes derived from the original tissue as demonstrated using transcriptome sequencing (RNA-seq) analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of these two cell lines, which overlapped with those of the SMG and SLG, were enriched in cysteine and methionine metabolism. Furthermore, we investigated the role of bone morphogenetic protein 9 (BMP9), also known as growth differentiation factor 2(Gdf2), on metabolic and fibrotic functions in the SMG and SLG. We demonstrated that iSMGCs and iSLGCs presented promising adipogenic and fibrotic responses upon BMP9/Gdf2 stimulation. Thus, our findings indicate that iSMGCs and iSLGCs faithfully reproduce characteristics of SMG and SLG cells and present a promising prospect for use in future study of salivary gland metabolism and fibrosis upon BMP9/Gdf2 stimulation.

[Regulatory Effect of All-Trans Retinoic Acid on the Expression of IL-1ß in Macrophages and the Mechanisms Involved].

Objective: To investigate the regulatory effect of all-trans retinoic acid (ATRA) on the expression interleukin-1ß (IL-1ß) in macrophages and the mechanisms involved. Methods: Macrophages were treated with 1 µmol/L ATRA for 24 h before RNA-Sequence. Differentially expressed genes (DEGs) were screened out and analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, gene ontology (GO) functional analysis, and protein-protein interaction networks (PPI) analysis. After treatment with different doses of ATRA for 24 h, the expression of IL-1ß was examined with qRT-PCR and Western blot. The activation of NF-κB signaling and caspase-1 was observed by Western blot and immunofluorescence staining. Results: Compared with the blank control group, a total of 71 DEGs of macrophages were upregulated in the ATRA treatment group. KEGG analysis showed that the up-regulated DEGs were involved in IL-17 signaling pathway, tumor necrosis factor (TNF) signaling pathway, etc. GO analysis indicated that the up-regulated DEGs were involved in the biological processes of the production of IL-1ß, response to lipopolysaccharide, etc. PPI analysis revealed that inflammatory cytokines, adhesion molecules, and chemokines were the key genes that ATRA acted on. In vitro experiments showed that ATRA promoted IL-1ß expression in macrophages in a concentration-dependent manner. The expression of p-NF-κB, NF-κB, and caspase-1 were significantly increased by ATRA compared with those of the control group ( P<0.05), and p-NF-κB translocated to the cell nucleus in the ATRA group. Conclusion: ATRA may promote the expression of IL-1ß by activating NF-κB signaling and caspase-1 in macrophages, this study may provide evidence for the immune regulatory function of ATRA on macrophages.

SATB2: A versatile transcriptional regulator of craniofacial and skeleton development, neurogenesis and tumorigenesis, and its applications in regenerative medicine.

SATB2 (special AT-rich sequence-binding protein 2) is a member of the special AT-rich binding protein family. As a transcription regulator, SATB2 mainly integrates higher-order chromatin organization. SATB2 expression appears to be tissue- and stage-specific, and is governed by several cellular signaling molecules and mediators. Expressed in branchial arches and osteoblast-lineage cells, SATB2 plays a significant role in craniofacial pattern and skeleton development. In addition to regulating osteogenic differentiation, SATB2 also displays versatile functions in neural development and cancer progression. As an osteoinductive factor, SATB2 holds great promise in improving bone regeneration toward bone defect repair. In this review, we have summarized our current understanding of the physiological and pathological functions of SATB2 in craniofacial and skeleton development, neurogenesis, tumorigenesis and regenerative medicine.

The submandibular and sublingual glands maintain oral microbial homeostasis through multiple antimicrobial proteins.

Introduction: Oral microbial homeostasis is a key factor affecting oral health, and saliva plays a significant role in maintaining oral microbial homeostasis. The submandibular gland (SMG) and sublingual gland (SLG) together produce the most saliva at rest. Organic ingredients, including antimicrobial proteins, are rich and distinctive and depend on the type of acinar cells in the SMG and SLG. However, the functions of the SMG and SLG in maintaining oral microbial homeostasis have been difficult to identify and distinguish, given their unique anatomical structures. Methods: In this study, we independently removed either the SMG or SLG from mouse models. SMGs were aseptically removed in three mice in the SMG-removal group, and SLGs were aseptically removed in three mice in the SLG-removal group. Three mice from the sham-operated group were only anesthetized and incised the skin. After one month, we analyzed their oral microbiome through 16S rRNA sequencing. And then, we analyzed each gland using proteomics and single-cell RNA sequencing. Results: Our study revealed that the microbiome balance was significantly disturbed, with decreased bacterial richness, diversity, and uniformity in the groups with the SMG or SLG removed compared with the sham-operated group. We identified eight secreted proteins in the SMG and two in the SLG that could be involved in maintaining oral microbial homeostasis. Finally, we identified multiple types of cells in the SMG and SLG (including serous acinar, mucinous acinar, ductal epithelial, mesenchymal, and immune cells) that express potential microbiota homeostasis regulatory proteins. Our results suggest that both the SMG and SLG play crucial roles in maintaining oral microbial homeostasis via excretion. Furthermore, the contribution of the SMG in maintaining oral microbial homeostasis appears to be superior to that of the SLG. These findings also revealed the possible antimicrobial function of gland secreta. Discussion: Our results suggest that control of oral microbial dysbiosis is necessary when the secretory function of the SMG or SLG is impaired. Our study could be the basis for further research on the prevention of oral diseases caused by microbial dysbiosis.

Evaluation of the efficiency of antibiotics in treating adult patients with symptomatic apical periodontitis: A protocol for systematic review and meta-analysis.

BACKGROUND: When a person feels dental pain, it brings great discomfort and damages the quality of life. Symptomatic apical periodontitis is identified as the most frequent cause that triggers dental pain. Symptomatic apical periodontitis arises from an infection or inflammation in the pulpless root canal structure. According to clinical guidelines, the primary form of therapy for such teeth entails removing the inflammation or infection source through local surgical procedures. Presently, systemic antibiotics are recommended only for cases where there is clear indication of an infectious spread or a systemic involvement. Therefore, this study aims to assess the efficacy and level of safety of using antibiotics to treat adult symptomatic apical periodontitis patients. METHODS: The present protocol study will conduct a search on electronic databases to look for randomized controlled trials (RCTs) that have evaluated the effectiveness and safety of antibiotics when used to treat adult patients with symptomatic apical periodontitis. The databases will be search from their beginning to April 2021. The search is not bound by publication status or language restrictions. The following databases will be searched: Web of Science, PubMed, the Cochrane Library, Chinese National Knowledge Infrastructure, and EMBASE. This study will employ ZETOC Conference Proceedings and OpenGrey to identify potential grey literature. Afterwards, 2 independent authors will select the studies, extract data from the studies, and conduct a risk assessment to check for bias. All discrepancies between the authors will be resolute via discussion involving a third independent author. The data synthesis and statistical analysis of this study will be done with the RevMan software (Version: 5.3). RESULTS: The present protocol report will provide high-quality evidence related to the efficacy and level of safety when using antibiotics to treat mature symptomatic apical periodontitis patients. CONCLUSION: The outcomes of the present study will update the evidence available for assessing the efficacy and safeness of using antibiotics to treat mature symptomatic apical periodontitis patients. ETHICS AND DISSEMINATION: This study does not require an ethical approval since individual patient data is not included in any form. REGISTRATION NUMBER: DOI 10.17605/OSF.IO/CVP8 M (https://osf.io/cvp8m/).

Special AT-rich sequence-binding protein 2 (Satb2) synergizes with Bmp9 and is essential for osteo/odontogenic differentiation of mouse incisor mesenchymal stem cells.

OBJECTIVES: Mouse incisor mesenchymal stem cells (MSCs) have self-renewal ability and osteo/odontogenic differentiation potential. However, the mechanism controlling the continuous self-renewal and osteo/odontogenic differentiation of mouse incisor MSCs remains unclear. Special AT-rich sequence-binding protein 2 (SATB2) positively regulates craniofacial patterning, bone development and regeneration, whereas SATB2 deletion or mutation leads to craniomaxillofacial dysplasia and delayed tooth and root development, similar to bone morphogenetic protein (BMP) loss-of-function phenotypes. However, the detailed mechanism underlying the SATB2 role in odontogenic MSCs is poorly understood. The aim of this study was to investigate whether SATB2 can regulate self-renewal and osteo/odontogenic differentiation of odontogenic MSCs. MATERIALS AND METHODS: Satb2 expression was detected in the rapidly renewing mouse incisor mesenchyme by immunofluorescence staining, quantitative RT-PCR and Western blot analysis. Ad-Satb2 and Ad-siSatb2 were constructed to evaluate the effect of Satb2 on odontogenic MSCs self-renewal and osteo/odontogenic differentiation properties and the potential role of Satb2 with the osteogenic factor bone morphogenetic protein 9 (Bmp9) in vitro and in vivo. RESULTS: Satb2 was found to be expressed in mesenchymal cells and pre-odontoblasts/odontoblasts. We further discovered that Satb2 effectively enhances mouse incisor MSCs self-renewal. Satb2 acted synergistically with the potent osteogenic factor Bmp9 in inducing osteo/odontogenic differentiation of mouse incisor MSCs in vitro and in vivo. CONCLUSIONS: Satb2 promotes self-renewal and osteo/odontogenic differentiation of mouse incisor MSCs. Thus, Satb2 can cooperate with Bmp9 as a new efficacious bio-factor for osteogenic regeneration and tooth engineering.