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1.
Stem Cells ; 42(7): 623-635, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38393380

ABSTRACT

Adipose-derived stem cells (ASCs) from diabetic osteoporosis (DOP) mice showed impaired osteogenic differentiation capacity. Recent studies have shown that in addition to antidiabetic drugs, sodium-glucose co-transporter inhibitor-2 (SGLT-2), empagliflozin, can play multipotent roles through various mechanisms of action. In this study, we aimed to investigate the effects and underlying mechanisms of empagliflozin on osteogenic differentiation of ASCs in DOP mice. Our results showed that osteogenic differentiation potential and autophagy activity weakened in DOP-ASCs when compared to controls. However, empagliflozin enhanced autophagy flux by promoting the formation of autophagosomes and acidification of autophagic lysosomes, resulting in an increase in LC3-II expression and a decrease in SQSTM1 expression. Furthermore, empagliflozin contributed to the reversal of osteogenesis inhibition in DOP-ASCs induced by a diabetic microenvironment. When 3-methyladenine was used to block autophagy activity, empagliflozin could not exert its protective effect on DOP-ASCs. Nonetheless, this study demonstrated that the advent of cellular autophagy attributed to the administration of empagliflozin could ameliorate the impaired osteogenic differentiation potential of ASCs in DOP mice. This finding might be conducive to the application of ASCs transplantation for promoting bone fracture healing and bone regeneration in patients with DOP.


Subject(s)
Autophagy , Benzhydryl Compounds , Cell Differentiation , Glucosides , Osteogenesis , Osteoporosis , Animals , Glucosides/pharmacology , Autophagy/drug effects , Osteogenesis/drug effects , Benzhydryl Compounds/pharmacology , Cell Differentiation/drug effects , Mice , Osteoporosis/pathology , Osteoporosis/drug therapy , Stem Cells/metabolism , Stem Cells/drug effects , Adipose Tissue/metabolism , Adipose Tissue/drug effects , Adipose Tissue/cytology , Mice, Inbred C57BL , Male
2.
Microb Pathog ; 197: 107066, 2024 Oct 22.
Article in English | MEDLINE | ID: mdl-39442818

ABSTRACT

OBJECTIVE: To understand the gender characteristics of oral lichen planus (OLP) by identifying the gender-specific salivary microbiome and its potential biomarkers. METHODS: A gender-based study was undertaken, commencing with the collection of saliva samples, followed by 16S rRNA gene sequencing, to explore the differences in the composition of saliva microbiome in OLP patients (40 males and 56 females) and healthy controls (40 males and 56 females), respectively. RESULTS: Both male and female OLP patients had significant differences in saliva microbiome composition from healthy controls, especially in female patients. Notably, Pseudomonas was only enriched in female patients. Rhodococcus (AUC: 0.91) and Pseudomonas (AUC: 0.97) had great potential as diagnostic biomarkers in male and female patients, respectively. The KEGG results showed metabolic dysfunction was more pronounced in female patients and a high level of microbial metabolism in diverse environments, ABC transporters, Quorum sensing and Two-component system. Capnocytophaga was negatively correlated with the erosion area in male patients. Neisseria was negatively correlated with the erosion area and Rothia was positively correlated with the pain level in female patients. CONCLUSIONS: Our study revealed gender-specific perturbation in salivary microbiome within OLP patients, suggesting that the male and female patients with OLP may have different pathogenesis.

3.
Pharmacol Res ; 204: 107214, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38763328

ABSTRACT

Studies have shown that the microbiota-gut-brain axis is highly correlated with the pathogenesis of depression in humans. However, whether independent oral microbiome that do not depend on gut microbes could affect the progression of depression in human beings remains unclear, neither does the presence and underlying mechanisms of the microbiota-oral-brain axis in the development of the condition. Hence this study that encompasses clinical and animal experiments aims at investigating the correlation between oral microbiota and the onset of depression via mediating the microbiota-oral-brain axis. We compared the oral microbial compositions and metabolomes of 87 patients with depressive symptoms versus 70 healthy controls. We found that the oral microbial and metabolic signatures were significantly different between the two groups. Significantly, germ-free (GF) mice transplanted with saliva from mice exposing to chronic restraint stress (CRS) displayed depression-like behavior and oral microbial dysbiosis. This was characterized by a significant differential abundance of bacterial species, including the enrichment of Pseudomonas, Pasteurellaceae, and Muribacter, as well as the depletion of Streptococcus. Metabolomic analysis showed the alternation of metabolites in the plasma of CRS-exposed GF mice, especially Eicosapentaenoic Acid. Furthermore, oral and gut barrier dysfunction caused by CRS-induced oral microbiota dysbiosis may be associated with increased blood-brain barrier permeability. Pseudomonas aeruginosa supplementation exacerbated depression-like behavior, while Eicosapentaenoic Acid treatment conferred protection against depression-like states in mice. These results suggest that oral microbiome and metabolic function dysbiosis may be relevant to the pathogenesis and pathophysiology of depression. The proposed microbiota-oral-brain axis provides a new way and targets for us to study the pathogenesis of depression.


Subject(s)
Depression , Dysbiosis , Stress, Psychological , Animals , Dysbiosis/metabolism , Depression/metabolism , Depression/microbiology , Depression/psychology , Depression/etiology , Male , Humans , Stress, Psychological/metabolism , Stress, Psychological/microbiology , Stress, Psychological/psychology , Female , Adult , Mice , Restraint, Physical/psychology , Mice, Inbred C57BL , Gastrointestinal Microbiome , Brain-Gut Axis , Mouth/microbiology , Middle Aged , Saliva/metabolism , Saliva/microbiology , Behavior, Animal , Blood-Brain Barrier/metabolism
4.
BMC Psychiatry ; 24(1): 246, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38566067

ABSTRACT

BACKGROUND: The Hospital Consultants' Job Stress Questionnaire (HCJSQ) has been widely used to assess sources and levels of job stress. However, its reliability and validity among Chinese dental workers have not been extensively studied. The objective of this study was to assess the reliability and validity of the HCJSQ specifically in Chinese dental workers. METHODS: The HCJSQ was used to explore the sources and the global ratings of job stress among Chinese dental workers. To assess the reliability and validity of the HCJSQ, various statistical measures were employed, including Cronbach's alpha coefficient, Spearman-Brown coefficient, Spearman correlation coefficient, exploratory factor analysis, confirmatory factor analysis, convergent validity, and discriminant validity. RESULTS: Of the participants, 526 (17.4%) reported high levels of stress, while 1,246 (41.3%) and 1,248 (41.3%) reported moderate and low levels of stress, respectively. The Cronbach's alpha coefficient for the modified HCJSQ was 0.903, and the Spearman-Brown coefficient was 0.904. Spearman correlation coefficient between individuals' items and the total score ranged from 0.438 to 0.785 (p < 0.05). Exploratory factor analysis revealed that three factors accounted for 60.243% of the total variance. Confirmatory factor analysis demonstrated factor loadings between 0.624 and 0.834 on the specified items. The fit indices of the confirmatory factor analysis indicated good model fit, with a Root Mean Square Error of Approximation of 0.064, Normative Fit Index of 0.937, Comparative Fit Index of 0.952, Incremental Fit Index of 0.952, Tucker-Lewis index of 0.941, and Goodness of Fit Index of 0.944. Additionally, the convergent validity and discriminant validity showed a good fit for the three-factor model. CONCLUSION: The results of this study confirm that Chinese dental workers experience high levels of stress, and the three-factor model of the HCJSQ proves to be a suitable instrument for evaluating the sources and levels of job stress among Chinese dental workers. Therefore, it is imperative that relevant entities such as hospitals, medical associations, and government take appropriate measures to address the existing situation.


Subject(s)
COVID-19 , Occupational Stress , Humans , Reproducibility of Results , Consultants , Pandemics , Psychometrics , China , Occupational Stress/diagnosis , Surveys and Questionnaires , Factor Analysis, Statistical , Hospitals
5.
Oral Dis ; 30(7): 4412-4425, 2024 10.
Article in English | MEDLINE | ID: mdl-38169073

ABSTRACT

OBJECTIVES: Recurrent aphthous ulcer (RAU) is a prevalent oral mucosal disease, affecting around 20% of the global population. It can greatly impair the quality of life for affected individuals. However, the exact etiology of RAU remains unknown. SUBJECTS AND METHODS: 16S rRNA sequencing (16S rRNA-seq) and non-targeted liquid chromatography-mass spectrometry (LC-MS) were employed to investigate the salivary microbiota and metabolic phenotype between RAU patients (N = 61) and healthy controls (HCs) (N = 105). RESULTS: Findings from 16S rRNA -seq indicated reduced oral microbial diversity in RAU patients compared to HCs, but increased interactions. Clinical variables did not show any significant association with the overall diversity of oral microbiota in RAU patients. However, significant correlations were observed between specific microorganisms and clinical variables. LC-MS results revealed dysregulation of amino acid, lipid, nucleotide, and caffeine metabolism in RAU patients. Furthermore, correlation analysis of 16S rRNA-seq and LC-MS data revealed a significant association between salivary microbiota and metabolites in RAU patients. CONCLUSIONS: Our study revealed notable differences in salivary microbiota and metabolic profiles between RAU patients and HCs, indicating a strong link between oral microbiota dysbiosis, metabolic disturbances, and the onset and progression of RAU.


Subject(s)
Dysbiosis , Microbiota , RNA, Ribosomal, 16S , Saliva , Stomatitis, Aphthous , Humans , Stomatitis, Aphthous/metabolism , Stomatitis, Aphthous/microbiology , Saliva/microbiology , Saliva/metabolism , Female , Male , Adult , Dysbiosis/microbiology , Case-Control Studies , Middle Aged , Phenotype , Young Adult , Chromatography, Liquid , Mass Spectrometry
6.
BMC Oral Health ; 24(1): 43, 2024 01 08.
Article in English | MEDLINE | ID: mdl-38191346

ABSTRACT

BACKGROUND: Chronic restraint stress (CRS) has iteratively been reported to be possibly implicated in the development of numerous cancer types. However, its role in oral squamous cell carcinoma (OSCC) has not been well elucidated. Here we intended to evaluate the role and mechanism. METHODS: The effects of CRS were investigated in xenograft models of OSCC by using transcriptome sequencing, LC-MS, ELISA and RT-PCR. Moreover, the role of CRS and ALDH3A1 on OSCC cells was researched by using Trans-well, flow cytometry, western blotting, immunofluorescence, ATP activity and OCR assay. Furthermore, immunohistochemical staining was employed to observe the cell proliferation and invasion of OSCC in xenotransplantation models. RESULTS: CRS promoted the progression of OSCC in xenograft models, stimulated the secretion of norepinephrine and the expression of ADRB2, but decreased the expression of ALDH3A1. Moreover, CRS changed energy metabolism and increased mitochondrial metabolism markers. However, ALDH3A1 overexpression suppressed proliferation, EMT and mitochondrial metabolism of OSCC cells. CONCLUSION: Inhibition of ALDH3A1 expression plays a pivotal role in CRS promoting tumorigenic potential of OSCC cells, and the regulatory of ALDH3A1 on mitochondrial metabolism may be involved in this process.


Subject(s)
Aldehyde Dehydrogenase , Mouth Neoplasms , Squamous Cell Carcinoma of Head and Neck , Stress, Psychological , Animals , Humans , Disease Models, Animal , Hormones , Restraint, Physical/adverse effects
7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(3): 423-429, 2021 May.
Article in Zh | MEDLINE | ID: mdl-34018360

ABSTRACT

OBJECTIVE: To investigate the differences in the osteogenic capacity of osteoporotic adipose-derived stem cells (OP-ASCs) and normal control adipose-derived stem cells (Ctrl-ASCs), and to examine the expression levels of RNA methyltransferase like 14 (Mettl14) and the Notch signaling molecule 1 (Notch1). METHODS: The osteoporosis (OP) model of SD rats was established with ovariectomy (OVX). Micro-CT, HE staining and Masson staining were performed to identify the successful establishment of the OP model, OP-ASCs and Ctrl-ASCs were isolated and cultured adherently. Then, the three-way differentiation capacity of the adipose-derived stem cells (ASCs) was determined through alizarin red staining, alcian blue staining and oil red O staining and flow cytometry was conducted to examine the surface antigens CD29, CD44, CD90, CD31, CD34, and CD45. Alizarin red staining and comparison of the mRNA and protein expression of Run-related transcription factor 2 (Runx2) were done to explore the differences in osteogenic potential of OP-ASCs and Ctrl-ASCs. Real-time PCR and Western blot were performed to explore the expression differences of Mettl14 and Notch1 at mRNA and protein levels between OP-ASCs and Ctrl-ASCs. RESULTS: Micro-CT, HE and Masson staining results showed that the number of trabecular bone decreased and the spacing increased in the tibias of the osteoporosis group (OP group) compared with those of the control group (Ctrl group), indicating that the OP model was established successfully. Three-way differentiation and flow cytometry results confirmed the successful isolation and culture of ASCs. After osteogenic induction, alizarin red staining showed that OP-ASCs had fewer number and more scattered distribution of mineralized nodules than Ctrl-ASCs did. The expression of Runx2 in OP-ASCs was lower than that in Ctrl-ASCs ( P<0.05). Mettl14 as well as Notch1 showed lower expression in OP-ASCs than they did in Ctrl-ASCs ( P<0.05). CONCLUSION: The osteogenic capacity of OP-ASCs was lower compared with that of Ctrl-ASCs, Mettl14 expression of OP-ASCs was decreased compared with that of Ctrl-ASCs, and the Notch signaling pathway was inhibited in OP-ASCs. The study helps build the foundation for further investigation in the specific mechanisms of Mettl14 and Notch1 during osteogenic differentiation of OP-ASCs.


Subject(s)
Osteogenesis , Stem Cells , Adipocytes , Adipose Tissue , Animals , Cell Differentiation , Cells, Cultured , Female , Humans , Methyltransferases , Rats , Rats, Sprague-Dawley , Receptor, Notch1/genetics
8.
Cancer Med ; 13(18): e70209, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39300932

ABSTRACT

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the predominant form of head and neck cancer, often diagnosed at late stages, resulting in a poor prognosis. Recent studies indicate a potential association between OSCC and microbial presence. Microorganisms have been identified in various tumors and lesions, including OSCC and oral potentially malignant disorders (OPMDs). Intralesional microbiota are considered important components of the tumor microenvironment (TME) and may contribute to carcinogenesis. METHODS: Sources were collected through thorough searches of databases PubMed and Embase. The review focused on microbial characteristics, potential origins, and their impact on cancer progression. RESULTS: Bacteria display varying abundance and diversity throughout the stages of OSCC and OPMDs. Intraleisional bacteria may have diverse sources, including not only oral plaque and saliva but also potentially the gut. Intralesional bacteria have both pro-carcinogenic and anti-carcinogenic effects, affecting processes like cell proliferation, invasion, and immune response. CONCLUSIONS: Intralesional microbiota are crucial in OSCC and OPMDs, influencing both disease progression and treatments. Despite their significance, challenges like inconsistent sampling and microbial identification remain. Future research is required to fully understand their role and improve clinical applications.


Subject(s)
Disease Progression , Mouth Neoplasms , Tumor Microenvironment , Humans , Mouth Neoplasms/microbiology , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/microbiology , Carcinoma, Squamous Cell/pathology , Microbiota , Bacteria , Squamous Cell Carcinoma of Head and Neck/microbiology , Squamous Cell Carcinoma of Head and Neck/pathology
9.
J Oral Microbiol ; 16(1): 2362313, 2024.
Article in English | MEDLINE | ID: mdl-38835338

ABSTRACT

Background: Burning mouth syndrome (BMS) is a chronic idiopathic facial pain with intraoral burning or dysesthesia. BMS patients regularly suffer from anxiety/depression, and the association of psychiatric symptoms with BMS has received considerable attention in recent years. The aims of this study were to investigate the potential interplay between psychiatric symptoms and BMS. Methods: Using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC/MS) to evaluate the oral microbiota and saliva metabolism of 40 BMS patients [including 29 BMS patients with depression or anxiety symptoms (DBMS)] and 40 age matched healthy control (HC). Results: The oral microbiota composition in BMS exhibited no significant differences from HC, although DBMS manifested decreased α-diversity relative to HC. Noteworthy was the discernible elevation in the abundance of proinflammatory microorganisms within the oral microbiome of individuals with DBMS. Parallel findings in LC/MS analyses revealed discernible disparities in metabolites between DBMS and HC groups. Principal differential metabolites were notably enriched in amino acid metabolism and lipid metabolism, exhibiting associations with infectious and immunological diseases. Furthermore, the integrated analysis underscores a definitive association between the oral microbiome and metabolism in DBMS. Conclusions: This study suggests possible future modalities for better understanding the pathogenesis and personalized treatment plans of BMS.

10.
Cell Signal ; 108: 110694, 2023 08.
Article in English | MEDLINE | ID: mdl-37141927

ABSTRACT

BACKGROUND: Diabetes mellitus (DM) microenvironment will accelerate the accumulation of Advanced glycation end products (AGEs), adipose-derived stem cells (ASCs) have poor osteogenesis in the DM microenvironment. Studies suggest autophagy plays a vital role in osteogenesis, but the mechanism of the altered osteogenic potential of ASCs has not been elucidated. Bone tissue engineering by ASCs is widely used in the treatment of bone defects with diabetic osteoporosis (DOP). Therefore, it is meaningful to explore the effect of AGEs on the osteogenic differentiation potential of ASCs and its potential mechanism for the repair of bone defects in DOP. MATERIALS AND METHODS: ASCs in C57BL/6 mice were isolated, cultured, then treated with AGEs, subsequently, cell viability and proliferation were detected through Cell Counting Kit 8 assay. 3-Methyladenine (3-MA), an autophagic inhibitor used to inhibit autophagic levels. Rapamycin (Rapa), an autophagy activator that further activated autophagy levels by inhibiting mTOR.The osteogenesis and autophagy changes of ASCs were analyzed by flow cytometry, qPCR, western blot, immunofluorescence, alkaline phosphatase (ALP) and alizarin red staining. RESULTS: AGEs reduced the autophagy level and osteogenic potential of ASCs. After 3-MA reduced autophagy, the osteogenic potential of ASCs also decreased. AGEs co-treatment with 3-MA, the levels of osteogenesis and autophagy reduced more significantly. When autophagy was activated by Rapa, it was found that it could rescue the reduced osteogenic potential of AGEs. CONCLUSIONS: AGEs reduce the osteogenic differentiation potential of ASCs through autophagy, and may provide a reference for the treatment of bone defects with diabetes osteoporosis.


Subject(s)
Diabetes Mellitus , Osteoporosis , Mice , Animals , Osteogenesis , Adipose Tissue , Mice, Inbred C57BL , Cell Differentiation , Stem Cells , Glycation End Products, Advanced/pharmacology , Cells, Cultured
11.
Exp Neurol ; 359: 114268, 2023 01.
Article in English | MEDLINE | ID: mdl-36343679

ABSTRACT

Chronic stress promotes tumor progression and may harm homeostasis of energy metabolism by disrupting key metabolic processes. Recently, emerging evidence that chemokines CXCL3 as a novel adipokine plays a new role in lipid metabolism and various human malignancies. However, the role and mechanism of the CXCL3 in oral squamous cell carcinoma (OSCC) progression and reprogramming lipid metabolism induced by chronic restraint stress is unclear. The analysis of transcriptome sequencing, LC-MS, GC-MS, CCK8, cell apoptosis assays, cell cycle analysis, qRT-PCR, ELISA, western blotting, immunofluorescence, immunohistochemistry, RNA interference and lentivirus transfection and a xenograft tumor growth and chronic restraint stress model were used to investigate the role of CXCL3 in the regulation of lipid metabolism and OSCC and explore the underlying molecular mechanisms. We showed that CXCL3 plays a critical role in in fatty acid de novo synthesis and tumor growth induced by chronic restraint stress. We demonstrated that chronic restraint stress promoted lipid accumulation, OSCC growth and metastasis in a mouse xenograft model. CXCL3 knockdown and FH535, an inhibitor of Wnt/ß-catenin pathway, could attenuate fatty acid de novo synthesis, cell proliferation and epithelial-mesenchymal transition induced by chronic restraint stress in OSCC cells. Our findings demonstrate that chronic restraint stress promotes the proliferation and metastasis of OSCC by reprogramming fatty acid metabolism via CXCL3 mediated Wnt/ß-catenin pathway. Our study provides novel insights to help understand the underlying mechanisms of CXCL3 in OSCC progression induced by chronic restraint stress.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Mice , Animals , Mouth Neoplasms/genetics , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , beta Catenin/metabolism , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Squamous Cell Carcinoma of Head and Neck/genetics , Cell Movement/genetics , Cell Line, Tumor , Wnt Signaling Pathway/genetics , Cell Proliferation , Carcinogenesis/genetics , Head and Neck Neoplasms/genetics , Lipid Metabolism , Fatty Acids , Gene Expression Regulation, Neoplastic , Chemokines, CXC/genetics , Chemokines, CXC/metabolism
12.
Genes Genet Syst ; 98(4): 191-200, 2023 Oct 24.
Article in English | MEDLINE | ID: mdl-37813646

ABSTRACT

N6-methyladenosine (m6A) modifications are the most abundant internal modifications of mRNA and have a significant role in various cancers; however, the m6A methylome profile of oral squamous cell carcinoma (OSCC) in the mRNA-wide remains unknown. In this study, we examined the relationship between m6A and OSCC. Four pairs of OSCC and adjacent normal tissues were compared by Methylated RNA immunoprecipitation sequencing (MeRIP-seq). Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Ingenuity Pathway Analysis (IPA) analyses were used to further analyze the MeRIP-seq data. A total of 2,348 different m6A peaks were identified in the OSCC group, including 85 m6A upregulated peaks and 2,263 m6A downregulated peaks. Differentially methylated m6A binding sites were enriched in the coding sequence in proximity to the stop codon of both groups. KEGG analysis revealed genes with upregulated m6A-modified sites in the OSCC group, which were prominently associated with the forkhead box O (FOXO) signaling pathway. Genes containing downregulated m6A-modified sites were significantly correlated with the PI3K/Akt signaling pathway, spliceosome, protein processing in the endoplasmic reticulum, and endocytosis. IPA analysis indicated that several genes with differential methylation peaks form networks with m6A regulators. Overall, this study established the mRNA-wide m6A map for human OSCC and indicated the potential links between OSCC and N6-methyladenosine modification.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Carcinoma, Squamous Cell/genetics , Squamous Cell Carcinoma of Head and Neck , Phosphatidylinositol 3-Kinases , Mouth Neoplasms/genetics , RNA, Messenger
13.
Front Immunol ; 13: 1005992, 2022.
Article in English | MEDLINE | ID: mdl-36211346

ABSTRACT

The oral epithelium's normal morphological structure and function play an important role in maintaining oral homeostasis, among which microbiota and chronic stress are key contributing factors. However, the effects of microbiota and chronic stress on the morphological structures and molecular function of oral homeostasis remain unclear. In this study, morphological staining was used to compare the tongue structure of specific pathogen-free and germ-free mice, and an integrated multi-omics analysis based on transcriptomics, proteomics, and metabolomics was performed to investigate the regulatory mechanisms of microbiota and chronic stress on oral homeostasis. We found that the morphological structure of the tongue in germ-free mice was disordered compared with in specific pathogen-free mice, especially in the epithelium. Multi-omics analysis indicated that differentially expressed molecules of the tongue between germ-free and specific pathogen-free mice were significantly enriched in the mitochondrial metabolic process and immune response. Interestingly, microbiota also significantly influenced the permeability of the oral epithelial barrier, represented by the differential expression of keratinization, and cell adhesion molecules. It was worth noting that the above changes in the tongue between specific pathogen-free and germ-free mice were more significant after chronic stress. Collectively, this is the first study to reveal that the microbiota might maintain oral homeostasis by reshaping the structure of the oral epithelial barrier and changing the function of molecular biology, a process that may be driven by the immune response and mitochondrial metabolic process of oral tissue. Furthermore, chronic stress can enhance the regulatory effects of microbiota on oral homeostasis.


Subject(s)
Microbiota , Animals , Homeostasis , Metabolomics , Mice , Microbiota/physiology , Permeability , Specific Pathogen-Free Organisms
14.
Cell Signal ; 87: 110138, 2021 11.
Article in English | MEDLINE | ID: mdl-34461277

ABSTRACT

BACKGROUND: The osteogenic differentiation ability of adipose-derived stem cells (ASCs) is attenuated in type 2 diabetic osteoporosis (Dop) mice. Several studies suggest autophagy and Notch signaling pathway play vital roles in cell proliferation, differentiation, and osteogenesis. However, the mechanisms of autophagy and Notch signaling in the osteogenic differentiation of Dop ASCs were unclear. Thus, it is meaningful to reveal potential correlations between autophagy, Notch signaling, and osteogenesis, and explore involved molecular mechanisms in Dop ASCs. MATERIALS AND METHODS: The diabetic osteoporosis C57BL/6 mouse model, which was confirmed by micro-CT and HE & Masson staining, was established through high-sugar and high-fat diet and streptozotocin injection. ASCs were obtained from the inguinal subcutaneous fat of Dop mice. The multi-differentiation potential of ASCs was evaluated by staining with Alizarin Red (osteogenesis), Oil Red O (adipogenesis), and Alcian blue (chondrogenesis). Cell viability was assessed by Cell Counting Kit-8 assay. Torin1, an inhibitor of mTOR, was used to stimulate the autophagy signaling pathway. DAPT, a γ-secretase inhibitor, was used to suppress Notch signaling pathway activity. Gene and protein expression of autophagy, Notch signaling pathway, and osteogenic factors were detected by real-time quantitative PCR, western blot, and immunofluorescence microscopy. RESULTS: Our findings showed autophagy and osteogenic differentiation ability of Dop ASCs exhibited downward trends that were both rescued by Torin1. Notch signaling was suppressed in Dop ASCs, but upregulated when autophagy was activated. After activation of autophagy, DAPT treatment led to decreased Notch signaling pathway activation and attenuated osteogenic differentiation ability in Dop ASCs. CONCLUSIONS: Downregulated autophagy suppressed Notch signaling, leading to a reduced osteogenic differentiation capacity of Dop ASCs, and Torin1 can rescue this process by activating autophagy. Our findings contribute to understanding the mechanism underlying impairment of the osteogenic differentiation ability of Dop ASCs.


Subject(s)
Diabetes Mellitus , Osteoporosis , Adipose Tissue/metabolism , Animals , Autophagy , Cell Differentiation/genetics , Cells, Cultured , Diabetes Mellitus/metabolism , Mice , Mice, Inbred C57BL , Osteogenesis/genetics , Osteoporosis/metabolism , Signal Transduction , Stem Cells
15.
Clin Implant Dent Relat Res ; 23(1): 117-130, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33528110

ABSTRACT

OBJECTIVES: To study the accuracy of partially guided and fully guided templates applied to implant surgery of anterior teeth. MATERIALS AND METHODS: Sixty patients who were scheduled to receive dental implant treatment in the anterior region were enrolled and randomly assigned to one of the following study groups (n = 20 each): routine implant-supported restoration treatment (control group, 30 implants), implant-supported restoration treatment using a partially guided template (test group 1, 36 implants), and implant-supported restoration treatment using a fully guided template (test group 2, 33 implants). The depth of implant was controlled for fully guided template. After implantation, planned implants and placed implants were superimposed using digital software, and the deviations (angular, coronal, apical, depth) were analyzed. Esthetic parameters were assessed at baseline, 6 months, and 1 year after the final restoration. Pink esthetic score (PES) and white esthetic score (WES) were respectively used to evaluate the soft tissue and restoration esthetic outcome. Each parameter of PES and WES is assessed with a 0-1-2 score with 2 being the best and 0 being the worst score. RESULTS: There were significant differences in all of the deviation parameters between the control group, test group 1, and test group 2 (p < 0.001). Mean angular, coronal, apical and depth deviations were all the highest in the control group (6.61 ± 1.09°, 1.05 ± 0.17 mm, 1.36 ± 0.13 mm, and 1.02 ± 0.13 mm, respectively), and lowest in test group 2 (2.05 ± 0.45°, 0.39 ± 0.12 mm, 0.28 ± 0.09 mm, and 0.24 ± 0.06 mm, respectively). At 1 year after the final restoration, the analysis revealed mean PES values of 7.09 ± 0.56 (control group), 8.39 ± 0.54 (test group 1), and 9.04 ± 0.35 (test group 2). The WES values were 7.24 ± 0.54 (control group), 8.47 ± 0.44 (test group 1), and 8.97 ± 0.38 (test group 2). At all examinations, the mean PES and WES values were both the highest in test group 2 and lowest in the control group. The PES and WES values recorded in the control group at baseline, 6 months, and 1 year after final restoration were significantly lower than those in test groups (p < 0.001). Moreover, the PES and WES values recorded in the test group 1 at baseline, 6 months, and 1 year after final restoration were significantly lower than those in test group 2 (p < 0.05). CONCLUSIONS: Digital surgical guides can improve the accuracy of the three-dimensional position of implants in the maxillary esthetic zone, the fully guided template has higher precision than that of the partially guided template, and plays an important role in obtaining the ideal esthetic outcome for maxillary anterior teeth.


Subject(s)
Dental Implants, Single-Tooth , Dental Implants , Crowns , Esthetics, Dental , Humans , Maxilla , Treatment Outcome
16.
Stem Cell Rev Rep ; 17(5): 1889-1904, 2021 10.
Article in English | MEDLINE | ID: mdl-34041696

ABSTRACT

OBJECTIVE: Although it has been demonstrated that adipose-derived stem cells (ASCs) from osteoporotic mice (OP-ASCs) exhibited impaired osteogenic differentiation potential, the molecular mechanism has not yet been elucidated. We found that Fzd6 was decreased in OP-ASCs compared with ASCs. This study investigates effects and underlying mechanisms of Fzd6 in the osteogenic potential of OP-ASCs, and explores methods to enhance osteogenic capacity of OP-ASCs. METHODS: Fzd6 overexpression and silencing lentiviruses were used to evaluate the role of Fzd6 in the osteogenic differentiation of OP-ASCs. Real-time PCR (qPCR) and western blotting (WB) was performed to detect the expression of Fzd6 and bone-related molecules, including runt-related transcription factor 2 (Runx2) and osteopontin (Opn). Alizarin red staining and Alkaline phosphatase (ALP) staining were performed following osteogenic induction. Microscopic CT (Micro-CT), hematoxylin and eosin staining (HE) staining, and Masson staining were used to assess the role of Fzd6 in osteogenic differentiation of osteoporosis (OP) mice in vivo. RESULTS: Expression of Fzd6 was decreased significantly in OP-ASCs. Fzd6 silencing down-regulated the osteogenic ability of OP-ASCs in vitro. Overexpression of Fzd6 rescued the impaired osteogenic capacity in OP-ASCs in vitro. We obtained similar results in vivo. CONCLUSIONS: Fzd6 plays an important role in regulating the osteogenic ability of OP-ASCs both in vivo and in vitro. Overexpression of Fzd6 promotes the osteogenic ability of OP-ASCs, which provides new insights for the prevention and treatment of OP mice.


Subject(s)
Osteogenesis , Stem Cells , Animals , Cell Differentiation/genetics , Mice , Osteogenesis/genetics
17.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(2): 170-176, 2020 Apr 01.
Article in Zh | MEDLINE | ID: mdl-32314891

ABSTRACT

OBJECTIVE: To study the precision of digital guide plates applied to the implant surgery of anterior teeth. METHODS: Fifty patients scheduled to receive implant restoration treatment in anterior teeth were enrolled in this study and divided into two groups (n=25, each group): those who were given routine implant restoration treatment (control group, 45 implants) and those who received implant restoration treatment using a digital guide plate (test group, 51 implants). After implantation, planned and placed implants were superimposed using digital software, and deviations (corona, apex, depth, degree) were analyzed. Esthetic parameters were assessed at 1 week (baseline), 6 month, and 1 year post final restoration. Pink esthetic (PES) and white esthetic (WES) scores were respectively used to evaluate the soft tissue and restoration esthetic outcome. RESULTS: The deviation parameters in the test group were significantly lower than those in the control group (P<0.05). PES and WES values recorded for the control group at 1 week, 6 month, and 1 year post final restoration were significantly lower than those in the test group (P<0.05). CONCLUSIONS: The digital guide plate can improve the accuracy of the three-dimensional position of implants in the maxillary esthetic zone. As such, this device may play an important role in obtaining the ideal aesthetic effects of maxillary anterior teeth.


Subject(s)
Dental Implants, Single-Tooth , Dental Implants , Crowns , Esthetics, Dental , Humans , Maxilla , Treatment Outcome
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