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1.
J Clin Periodontol ; 51(4): 417-430, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38016486

RESUMO

AIM: This Mendelian randomization (MR) study was performed to explore the potential bidirectional causal relationship between the gut microbiome (GM) and periodontitis. MATERIALS AND METHODS: We used genetic instruments from the genome-wide association study of European descent for periodontitis from the GeneLifestyle Interactions in Dental Endpoints (GLIDE) consortium (17,353 cases and 28,210 controls) and the FinnGen consortium (4434 cases and 259,234 controls) to investigate the causal relationship with GM (the MiBioGen consortium, 18,340 samples), and vice versa. Several MR techniques, which include inverse variance weighting (IVW), MR-Egger, weighted median, simple mode and weighted mode approaches, were employed to investigate the causal relationship between the exposures and the outcomes. Cochran's Q-test was performed to detect heterogeneity. The MR-Egger regression intercept and MR pleiotropy residual sum and outlier test (MR-PRESSO) were conducted to test potential horizontal pleiotropy. Leave-one-out sensitivity analyses were used to assess the stabilities of single nucleotide polymorphisms (SNPs). Finally, the IVW results from the two databases were analysed using meta-analysis. RESULTS: We confirmed three potential causal relationships between GM taxa and periodontitis at the genus level. Among them, the genera Alistipes and Holdemanella were genetically associated with an increased risk of periodontitis. In reverse, periodontitis may lead to a decreased abundance of the genus Ruminococcaceae UCG014. CONCLUSIONS: The demonstration of a causal link between GM and periodontitis provides compelling evidence, highlighting the interconnectivity and interdependence of the gut-oral and oral-gut axes.


Assuntos
Microbioma Gastrointestinal , Periodontite , Humanos , Microbioma Gastrointestinal/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Causalidade , Periodontite/genética
2.
Oral Dis ; 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38852165

RESUMO

OBJECTIVES: Periodontitis seriously affects oral-related quality of life and overall health. Long intergenic non-coding RNA 01126 (LINC01126) is aberrantly expressed in periodontitis tissues. This study aimed to explore the possible pathogenesis of LINC01126 in periodontitis. METHODS: Inflammatory model of human gingival fibroblasts (HGFs) was established. Cell Counting Kit-8 (CCK-8), wound healing assay, and flow cytometry were utilized to detect biological roles of LINC01126. Binding site of miR-655-3p to LINC01126 and IL-6 was predicted. Then, subcellular localization of LINC01126 and the binding ability of miR-655-3p to LINC01126 and IL-6 in HGFs were verified. Hematoxylin-Eosin (H&E) staining and immunohistochemistry (IHC) staining were utilized to detect tissue morphology and proteins expression of clinical samples. RESULTS: LINC01126 silencing can alleviate cell inflammation induced by lipopolysaccharide derived from Porphyromonas gingivalis, reduce cell apoptosis, and promote cell migration. As a "sponge" for miR-655-3p, LINC01126 inhibits its binding to mRNA of IL-6, thereby promoting inflammation progression and JAK2/STAT3 pathway activation. Quantitative real-time PCR, Western Blot, and IHC results of clinical tissue samples further confirmed that miR-655-3p expression was down-regulated and IL-6/JAK2/STAT3 was abnormally activated in periodontitis tissues. CONCLUSIONS: In summary, serving as an endogenous competitive RNA of miR-655-3p, LINC01126 promotes IL-6/JAK2/STAT3 pathway activation, thereby promoting periodontitis pathogenesis.

3.
Biochemistry ; 62(6): 1138-1144, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36821831

RESUMO

Poly-ADP-ribose (PAR) is a natural type of polymer derived from enzymatic reactions catalyzed by cellular poly(ADP-ribose) polymerases (PARPs). Given its notable solubility and biocompatibility, the PAR polymer may function as effective carriers for therapeutics in addition to modulating biomolecular interactions in cells. To explore its therapeutic potential, we herein developed a PAR polymer-based bispecific antibody targeting both human epidermal growth factor receptor 2 (HER2) and T-cell CD3 antigens. This was accomplished by conjugating anti-HER2 and anti-CD3 monoclonal antibodies to azido-functionalized PAR polymers through click chemistry. The generated PAR polymer-anti-HER2/anti-CD3 antibody conjugate could not only bind specifically to both HER2- and CD3-expressing target cells but also display potent cytotoxicity against HER2-positive breast cancer cells in the presence of non-activated human peripheral blood mononuclear cells (PBMCs). Functionalized PAR polymers provide a new strategy for synthesizing bispecific antibodies and may enable generation of PAR polymer-based conjugates with unique pharmacological activities for biomedical applications.


Assuntos
Anticorpos Biespecíficos , Poli Adenosina Difosfato Ribose , Humanos , Poli Adenosina Difosfato Ribose/metabolismo , Polímeros , Leucócitos Mononucleares , Poli(ADP-Ribose) Polimerases/metabolismo
4.
J Periodontal Res ; 58(3): 529-543, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36941720

RESUMO

OBJECTIVE: This study aims to investigate the differences in the epigenomic patterns of N6-methyladenosine (m6A) methylation in gingival tissues between patients with periodontitis (PD) and healthy controls, identifying potential biomarkers. BACKGROUND: As a multifactorial disease, PD involves multiple genetic and environmental effects. The m6A modification is the most prevalent internal mRNA modification and linked to various inflammatory diseases. However, the m6A modification pattern and m6A-related signatures in PD remain unclear. MATERIALS AND METHODS: An m6A microarray of human gingival tissues was conducted in eight subjects: four diagnosed with PD and four healthy controls. Microarray analysis was performed to identify the differentially m6A methylated mRNAs (DMGs) and the differentially expressed mRNAs (DEGs). The differentially methylated and expressed mRNAs (DMEGs) were subjected to functional enrichment analysis by Metascape. The weighted gene co-expression network analysis (WGCNA) algorithm, the least absolute shrinkage and selection operator (LASSO) regression, and univariate logistic regression were performed to identify potential biomarkers. The cell type localization of the target genes was determined using single-cell RNA-seq (scRNA-seq) analysis. The m6A methylation level and gene expression of hub genes were subsequently verified by m6A methylated RNA immunoprecipitation (MeRIP) and quantitative real-time PCR (qRT-PCR). RESULTS: In total, 458 DMGs, 750 DEGs, and 279 DMEGs were identified based on our microarray. Pathway analyses conducted for the DMEGs revealed that biological functions were mainly involved in the regulation of stem cell differentiation, ossification, circadian rhythm, and insulin secretion pathways. Besides, the genes involved in crucial biological processes were mainly expressed in fibroblast and epithelial cells. Furthermore, the m6A methylation and expression levels of two hub biomarkers (DNER and GNL2) were validated. CONCLUSION: The current study exhibited a distinct m6A epitranscriptome, identified and verified two PD-related biomarkers (DNER and GNL2), which may provide novel insights into revealing the new molecular mechanisms and latent targets of PD.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Humanos , Transcriptoma/genética , Análise em Microsséries , Diferenciação Celular , Células Epiteliais , Proteínas do Tecido Nervoso , Receptores de Superfície Celular
5.
J Periodontal Res ; 58(5): 968-985, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37357608

RESUMO

BACKGROUND AND OBJECTIVES: Periodontitis, a prevalent chronic inflammatory condition, poses a significant risk of tooth loosening and subsequent tooth loss. Within the realm of programmed cell death, a recently recognized process known as necroptosis has garnered attention for its involvement in numerous inflammatory diseases. Nevertheless, its correlation with periodontitis is indistinct. Our study aimed to identify necroptosis-related lncRNAs and crucial lncRNA-miRNA-mRNA regulatory axes in periodontitis to further understand the pathogenesis of periodontitis. MATERIALS AND METHODS: Gene expression profiles in gingival tissues were acquired from the Gene Expression Omnibus (GEO) database. Selecting hub necroptosis-related lncRNA and extracting the key lncRNA-miRNA-mRNA axes based on the ceRNA network by adding novel machine-learning models based on conventional analysis and combining qRT-PCR validation. Then, an artificial neural network (ANN) model was constructed for lncRNA in regulatory axes, and the accuracy of the model was validated by receiver operating characteristic (ROC) curve analysis. The clinical effect of the model was evaluated by decision curve analysis (DCA). Weighted correlation network analysis (WGCNA) and single-sample gene set enrichment analysis (ssGSEA) was performed to explore how these lncRNAs work in periodontitis. RESULTS: Seven hub necroptosis-related lncRNAs and three lncRNA-miRNA-mRNA regulatory axes (RP11-138A9.1/hsa-miR-98-5p/ZBP1 axis, RP11-96D1.11/hsa-miR-185-5p/EZH2 axis, and RP4-773 N10.4/hsa-miR-21-5p/TLR3 axis) were predicted. WGCNA revealed that RP11-138A9.1 was significantly correlated with the "purple module". Functional enrichment analysis and ssGSEA demonstrated that the RP11-138A9.1/hsa-miR-98-5p/ZBP1 axis is closely related to the inflammation and immune processes in periodontitis. CONCLUSION: Our study predicted a crucial necroptosis-related regulatory axis (RP11-138A9.1/hsa-miR-98-5p/ZBP1) based on the ceRNA network, which may aid in elucidating the role and mechanism of necroptosis in periodontitis.


Assuntos
MicroRNAs , Periodontite , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Necroptose/genética , Periodontite/genética , MicroRNAs/genética , RNA Mensageiro
6.
Cytokine ; 159: 156014, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36084605

RESUMO

OBJECTIVES: This bioinformatics study is aimed at identifying cross-talk genes, pyroptosis-related genes, and related pathways between periodontitis (PD) and diabetes mellitus (DM), which includes type 1 diabetes (T1DM) and type 2 diabetes (T2DM). METHODS: GEO datasets containing peripheral blood mononuclear cell (PBMC) data of PD and DM were acquired. After batch correction and normalization, differential expression analysis was performed to identify the differentially expressed genes (DEGs). And cross-talk genes in the PD-T1DM pair and the PD-T2DM pair were identified by overlapping DEGs with the same trend in each pair. The weighted gene coexpression network analysis (WGCNA) algorithm helped locate the pyroptosis-related genes that are related to cross-talk genes. Receiver-operating characteristic (ROC) curve analysis confirmed the predictive accuracy of these hub genes in diagnosing PD and DM. The correlation between hub genes and the immune microenvironment of PBMC in these diseases was investigated by Spearman correlation analysis. The experimentally validated protein-protein interaction (PPI) and gene-pathway network were constructed. Subnetwork analysis helped identify the key pathway connecting DM and PD. RESULTS: Hub genes in the PD-T1DM pair (HBD, NLRC4, AIM2, NLRP2) and in the PD-T2DM pair (HBD, IL-1Β, AIM2, NLRP2) were identified. The similarity and difference in the immunocytes infiltration levels and immune pathway scores of PD and DM were observed. ROC analysis showed that AIM2 and HBD exhibited pleasant discrimination ability in all diseases, and the subnetwork of these genes indicated that the NOD-like receptor signaling pathway is the most potentially relevant pathway linking PD and DM. CONCLUSION: HBD and AIM2 could be the most relevant potential cross-talk and pyroptosis-related genes, and the NOD-like receptor signaling pathway could be the top candidate molecular mechanism linking PD and DM, supporting a potential pathophysiological relationship between PD and DM.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Periodontite , Biologia Computacional , Análise de Dados , Diabetes Mellitus Tipo 2/genética , Perfilação da Expressão Gênica , Humanos , Leucócitos Mononucleares , Proteínas NLR/genética , Piroptose/genética
7.
Biomacromolecules ; 23(12): 5267-5272, 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36350184

RESUMO

Poly-ADP-ribose (PAR) is a naturally occurring form of polymers synthesized through enzymatic reactions catalyzed by poly(ADP-ribose) polymerases (PARPs). It is known for regulating various important cellular signaling pathways and processes. As a water soluble and biocompatible type of polymer, PAR may hold promise for safe and efficient delivery of therapeutics. To explore the therapeutic potential of PAR polymers, we herein generate PAR polymers conjugated with human granulocyte colony-stimulating factor (GCSF) protein by harnessing human PARP1-catalyzed auto-poly-ADP-ribosylation and a clickable analogue of nicotinamide adenine dinucleotide (NAD+). The resulting PAR polymer-based conjugate with multivalent GCSF ligands exhibits a potent cell proliferative activity. Notably, mice treated with a single dose of the PAR polymer-GCSF conjugate show sustained high levels of neutrophil in blood for 11 days, demonstrating excellent in vivo efficacy. Functionalized PAR polymers may provide new scaffolds for conjugating with therapeutic proteins or peptides toward improved pharmacological activities.


Assuntos
Poli Adenosina Difosfato Ribose , Polímeros , Humanos , Camundongos , Animais , Poli Adenosina Difosfato Ribose/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , NAD/metabolismo , Fator Estimulador de Colônias de Granulócitos/farmacologia
8.
J Periodontal Res ; 57(5): 977-990, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35839262

RESUMO

BACKGROUND AND OBJECTIVE: Published studies proved that both pyroptosis and periodontitis owned a substantial relationship with immunity, and recent research revealed a solid correlation between periodontitis and pyroptosis. While abundant findings have confirmed pyroptosis has a strong impact on the tumor microenvironment, the function of pyroptosis in influencing the periodontitis immune microenvironment remains poorly understood. Thus, we aimed to identify pyroptosis-related genes whose expression signature can well discriminate periodontitis from healthy controls and to comprehend the role of pyroptosis in the periodontitis immune microenvironment. MATERIALS AND METHODS: The periodontitis-related datasets were acquired from the Gene Expression Omnibus (GEO) database. A series of bioinformatics analyses were conducted to investigate the underlying mechanism of pyroptosis in the periodontitis immune microenvironment. Infiltrating immunocytes, immunological reaction gene sets, and the human leukocyte antigen (HLA) gene were all investigated as potential linkages between periodontitis immune microenvironment and pyroptosis. RESULTS: Twenty-one pyroptosis-related genes were dysregulated. A four-mRNA combined classification model was constructed, and the receiver operating characteristic (ROC) curve analysis demonstrated its prominent classification capabilities. Subsequently, the mRNA levels of the four hub markers (CYCS, CASP3, NOD2, CHMP4B) were validated by quantitative real-time PCR (qRT-PCR). The correlation coefficients between each hub gene and immune characteristics were calculated, and CASP3 exhibited the most significant correlations with the immune characteristics. Furthermore, distinct pyroptosis-related expression patterns were revealed, along with immunological features of each pattern. Afterward, we discovered 1868 pyroptosis phenotype-related genes, 134 of which were related to immunity. According to the functional enrichment analysis, these 134 genes were closely related to cytokine signaling in immune system, and defense response. Finally, a co-expression network was constructed via the 1868 gene expression profiles. CONCLUSION: Four hub mRNAs (CYCS, CASP3, NOD2, and CHMP4B) formed a classification model and concomitant results revealed the crucial role of pyroptosis in the periodontitis immune microenvironment, providing fresh insights into the etiopathogenesis of periodontitis and potential immunotherapy.


Assuntos
Periodontite , Piroptose , Caspase 3 , Humanos , Periodontite/genética , Piroptose/genética , RNA Mensageiro , Microambiente Tumoral/genética
9.
J Periodontal Res ; 57(4): 811-823, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35653494

RESUMO

OBJECTIVE: To explore the role of Marginal Zone B and B-1 Cell-Specific Protein (MZB1), a novel molecule associated with periodontitis, in migration of human periodontal ligament cells (hPDLCs) and alveolar bone orchestration. BACKGROUND: MZB1 is an ER-localized protein and its upregulation has been found to be associated with a variety of human diseases. However, few studies have investigated the effect and mechanism of MZB1 on hPDLCs in periodontitis. METHODS: Gene expression profiles in human gingival tissues were acquired from the Gene Expression Omnibus (GEO) database, and candidate molecules were then selected through bioinformatic analysis. Subsequently, we identified the localization and expression of MZB1 in human gingival tissues, mice, and hPDLCs by immunofluorescence, RT-qPCR, and Western blot. Dual-luciferase reporter assay was applied to assess the binding of miR-185-5p to MZB1. Furthermore, the effects of MZB1 on cell migration, proliferation, and apoptosis in vitro were investigated by wound-healing assay, transwell assay, CCK-8 assay, and flow cytometry analysis. Finally, Micro-CT analysis and H&E staining were performed to examine the effects of MZB1 on alveolar bone loss in vivo. RESULTS: Bioinformatic analysis discovered that MZB1 was one of the most significantly increased genes in periodontitis patients. MZB1 was markedly increased in the gingival tissues of periodontitis patients, in the mouse models, and in the hPDLCs treated with lipopolysaccharide of Porphyromonas gingivalis (LPS-PG). Furthermore, in vitro experiments showed that MZB1, as a target gene of miR-185-5p, inhibited migration of hPDLCs. Overexpression of MZB1 specifically upregulated the phosphorylation of p65, while pretreatment of MZB1-overexpressed hPDLCs with PDTC (NF-κB inhibitor) notably reduced the p-p65 level and promoted cell migration. In addition, the mRNA expression levels of alkaline phosphatase (ALP) and Runt-related transcription factor 2 (Runx2) were inhibited in MZB1-overexpressed hPDLCs and miR-185-5p inhibitor treated hPDLCs, respectively. In vivo experiments showed that knockdown of MZB1 alleviated the loss of alveolar bone. CONCLUSION: As a target gene of miR-185-5p, MZB1 plays a crucial role in inhibiting the migration of hPDLCs through NF-κB signaling pathway and deteriorating alveolar bone loss.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Perda do Osso Alveolar , MicroRNAs , Periodontite , Proteínas Adaptadoras de Transdução de Sinal/genética , Perda do Osso Alveolar/genética , Perda do Osso Alveolar/metabolismo , Animais , Células Cultivadas , Humanos , Camundongos , MicroRNAs/genética , NF-kappa B/metabolismo , Osteogênese , Ligamento Periodontal/metabolismo , Periodontite/genética , Periodontite/metabolismo , Transdução de Sinais/genética
10.
Mater Today Bio ; 25: 100990, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38371466

RESUMO

Background: Human-treated dentin matrix (hTDM) has recently been studied as a natural extracellular matrix-based biomaterial for dentin pulp regeneration. However, porcine-treated dentin matrix (pTDM) is a potential alternative scaffold due to limited availability. However, there is a dearth of information regarding the protein composition and underlying molecular mechanisms of pTDM.Methods: hTDM and pTDM were fabricated using human and porcine teeth, respectively, and their morphological characteristics were examined using scanning electron microscopy. Stem cells derived from human exfoliated deciduous teeth (SHEDs) were isolated and characterized using flow cytometry and multilineage differentiation assays. SHEDs were cultured in three-dimensional environments with hTDM, pTDM, or biphasic hydroxyapatite/tricalcium phosphate. The expression of odontogenesis markers in SHEDs were assessed using real-time polymerase chain reaction and immunochemical staining. Subsequently, SHEDs/TDM and SHEDs/HA/TCP complexes were transplanted subcutaneously into nude mice. The protein composition of pTDM was analyzed using proteomics and compared to previously published data on hTDM.Results: pTDM and hTDM elicited comparable upregulation of odontogenesis-related genes and proteins in SHEDs. Furthermore, both demonstrated the capacity to stimulate root-related tissue regeneration in vivo. Proteomic analysis revealed the presence of 278 protein groups in pTDM, with collagens being the most abundant. Additionally, pTDM and hTDM shared 58 identical proteins, which may contribute to their similar abilities to induce odontogenesis. Conclusions: Both hTDM and pTDM exhibit comparable capabilities in inducing odontogenesis, potentially owing to their distinctive bioactive molecular networks.

11.
Inflammation ; 46(5): 1932-1951, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37311930

RESUMO

Periodontitis is a prevalent and persistent inflammatory condition that impacts the supporting tissues of the teeth, including the gums and bone. Recent research indicates that mitochondrial dysfunction may be involved in the onset and advancement of periodontitis. The current work sought to reveal the interaction between mitochondrial dysfunction and the immune microenvironment in periodontitis. Public data were acquired from MitoCarta 3.0, Mitomap, and GEO databases. Hub markers were screened out by five integrated machine learning algorithms and verified by laboratory experiments. Single-cell sequencing data were utilized to unravel cell-type specific expression levels of hub genes. An artificial neural network model was constructed to discriminate periodontitis from healthy controls. An unsupervised consensus clustering algorithm revealed mitochondrial dysfunction-related periodontitis subtypes. The immune and mitochondrial characteristics were calculated using CIBERSORTx and ssGSEA algorithms. Two hub mitochondria-related markers (CYP24A1 and HINT3) were identified. Single-cell sequencing data revealed that HINT3 was primarily expressed in dendritic cells, while CYP24A1 was mainly expressed in monocytes. The hub genes based artificial neural network model showed robust diagnostic performance. The unsupervised consensus clustering algorithm revealed two distinct mitochondrial phenotypes. The hub genes exhibited a strong correlation with the immune cell infiltration and mitochondrial respiratory chain complexes. The study identified two hub markers that may serve as potential targets for immunotherapy and provided a novel reference for future investigations into the function of mitochondria in periodontitis.


Assuntos
Periodontite , Humanos , Vitamina D3 24-Hidroxilase , Mitocôndrias , Biologia Computacional , Aprendizado de Máquina
12.
Int J Med Sci ; 9(10): 862-71, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23155360

RESUMO

Dental follicle stem cells are a group of cells possessing osteogenic, adipogenetic and neurogenic differentiations, but the specific mechanism underlying the multilineage differentiation remains still unclear. Great attention has been paid to bone morphogenetic protein-9 (BMP-9) due to its potent osteogenic activity. In the present study, rat dental follicle stem cells were isolated and purified, and cells of passage 3 underwent adenovirus mediated BMP-9 gene transfection to prepare dental follicle stem cells with stable BMP-9 expression. Detection of alkaline phosphatase (ALP) and calcium deposition showed dental follicle stem cells transfected with BMP-9 gene could significantly promote the osteogenesis. In addition, SB203580 and PD98059 were employed to block the p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal-regulated kinase (ERK1/2), respectively. Detection of ALP and calcium deposition revealed the BMP-9 induced osteogenic differentiation of dental follicle stem cells depended on MAPK signaling pathway.


Assuntos
Saco Dentário , Fator 2 de Diferenciação de Crescimento , Osteogênese/genética , Células-Tronco , Fosfatase Alcalina/metabolismo , Animais , Cálcio/metabolismo , Diferenciação Celular , Células Cultivadas , Saco Dentário/citologia , Saco Dentário/crescimento & desenvolvimento , Saco Dentário/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Flavonoides/farmacologia , Expressão Gênica/efeitos dos fármacos , Fator 2 de Diferenciação de Crescimento/genética , Fator 2 de Diferenciação de Crescimento/metabolismo , Imidazóis/farmacologia , Osteoblastos/citologia , Osteoblastos/metabolismo , Piridinas/farmacologia , Ratos , Células-Tronco/citologia , Células-Tronco/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Front Immunol ; 13: 1042484, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389665

RESUMO

Background: Periodontitis (PD), an age-related disease, is characterized by inflammatory periodontal tissue loss, and with the general aging of the global population, the burden of PD is becoming a major health concern. Nevertheless, the mechanism underlying this phenomenon remains indistinct. We aimed to develop a classification model for PD and explore the relationship between aging subtypes and the immune microenvironment for PD based on bioinformatics analysis. Materials and Methods: The PD-related datasets were acquired from the Gene Expression Omnibus (GEO) database, and aging-related genes (ARGs) were obtained from the Human Aging Genomic Resources (HAGR). Four machine learning algorithms were applied to screen out the hub ARGs. Then, an artificial neural network (ANN) model was constructed and the accuracy of the model was validated by receiver operating characteristic (ROC) curve analysis. The clinical effect of the model was evaluated by decision curve analysis (DCA). Consensus clustering was employed to determine the aging expression subtypes. A series of bioinformatics analyses were performed to explore the PD immune microenvironment and its subtypes. The hub aging-related modules were defined using weighted correlation network analysis (WGCNA). Results: Twenty-seven differentially expressed ARGs were dysregulated and a classifier based on four hub ARGs (BLM, FOS, IGFBP3, and PDGFRB) was constructed to diagnose PD with excellent accuracy. Subsequently, the mRNA levels of the hub ARGs were validated by quantitative real-time PCR (qRT-PCR). Based on differentially expressed ARGs, two aging-related subtypes were identified. Distinct biological functions and immune characteristics including infiltrating immunocytes, immunological reaction gene sets, the human leukocyte antigen (HLA) gene, and immune checkpoints were revealed between the subtypes. Additionally, the black module correlated with subtype-1 was manifested as the hub aging-related module and its latent functions were identified. Conclusion: Our findings highlight the critical implications of aging-related genes in modulating the immune microenvironment. Four hub ARGs (BLM, FOS, IGFBP3, and PDGFRB) formed a classification model, and accompanied findings revealed the essential role of aging in the immune microenvironment for PD, providing fresh inspiration for PD etiopathogenesis and potential immunotherapy.


Assuntos
Perfilação da Expressão Gênica , Periodontite , Humanos , Receptor beta de Fator de Crescimento Derivado de Plaquetas , Biologia Computacional , Envelhecimento/genética , Periodontite/genética
14.
Int J Biol Macromol ; 217: 944-955, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-35908675

RESUMO

Developing advanced dressings that integrate multiple functions is one of the major challenges in current clinical wound treatment. In this study, Xanthan gum (XG) and polyacrylamide (PAAm) materials were used to prepare hydrogel dressings by one-pot method. With the combination of the PAAm network and the XG network, the PAAm-XG hydrogels showed the tensile strength of 0.36 MPa and the stretchability as large as 2078 %. The prepared PAAm-XG hydrogels had excellent water uptake efficiency with the swelling ratio of 1200 %. Besides, the developed dressings possessed outstanding biocompatibility, universal adhesion and self-healing ability. More importantly, the PAAm-XG hydrogels can be successfully loaded with Cefixime and human recombinant epidermal growth factor, and these loaded hydrogels released these bioactive molecules in sustained ways. As a result, both E. coli and S. aureus bacteria were inactivated after contacting with the Cefixime-loaded hydrogels for 24 h. Furthermore, in vivo data demonstrated that the PAAm-XG hydrogel dressings significantly accelerated the wound healing in a mouse model. All of these indicate that the multifunctional PAAm-XG hydrogels are promising candidates for wound treatment.


Assuntos
Hidrogéis , Staphylococcus aureus , Resinas Acrílicas , Animais , Bandagens , Cefixima , Escherichia coli , Humanos , Camundongos , Polissacarídeos Bacterianos
15.
Stem Cell Res Ther ; 13(1): 234, 2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35659736

RESUMO

BACKGROUND: Bio-root regeneration is a promising treatment for tooth loss. It has been reported that dental-derived stem cells are effective seed cells for bio-root construction, but further applications are limited by their few sources. Human adipose tissues have a wide range of sources and numerous studies have confirmed the ability of adipose-derived stromal/stem cells (ASCs) in regenerative medicine. In the current study, the odontogenic capacities of ASCs were compared with dental-derived stem cells including dental follicle cells (DFCs), and stem cells from human exfoliated deciduous teeth (SHEDs). METHODS: The biological characteristics of ASCs, DFCs, and SHEDs were explored in vitro. Two-dimensional (2D) and three-dimensional (3D) cultures were compared in vitro. Odontogenic characteristics of porcine-treated dentin matrix (pTDM) induced cells under a 3D microenvironment in vitro were compared. The complexes (cell/pTDM) were transplanted subcutaneously into nude mice to verify regenerative potential. RNA sequencing (RNA-seq) was used to explore molecular mechanisms of different seed cells in bio-root regeneration. RESULTS: 3D culture was more efficient in constructing bio-root complexes. ASCs exhibited good biological characteristics similar to dental-derived stem cells in vitro. Besides, pTDM induced ASCs presented odontogenic ability similar to dental-derived stem cells. Furthermore, 3D cultured ASCs/pTDM complex promoted regeneration of dentin-like, pulp-like, and periodontal fiber-like tissues in vivo. Analysis indicated that PI3K-Akt, VEGF signaling pathways may play key roles in the process of inducing ASCs odontogenic differentiation by pTDM. CONCLUSIONS: ASCs are potential seed cells for pTDM-induced bio-root regeneration, providing a basis for further research and application.


Assuntos
Dentina , Raiz Dentária , Animais , Diferenciação Celular , Polpa Dentária , Dentina/metabolismo , Camundongos , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Células-Tronco , Suínos
16.
Front Microbiol ; 13: 875091, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36160195

RESUMO

Aim: To assess the contribution of polymicrobial disruption of host homeostasis to periodontitis progression in orthodontic wire ligation murine model. Methods: Orthodontic wire rings were inserted between the first and second molars of mice for 18 days for the orthodontic wire ligation mouse model, and Pg injection model and Pg-LPS injection model were used as controls. Alveolar bone loss and periodontal inflammation were analyzed by micro-CT, histological staining and qRT-PCR. Further, pyrosequencing of 16S rRNA gene amplicon was used to analyze the development of oral microorganism dysbiosis in the mice. Results: Micro-CT, TRAP staining and qRT-PCR showed that orthodontic wire ligation model led to more severe alveolar bone loss than Pg and Pg-LPS models.H&E staining and qRT-PCR demonstrated that stronger inflammatory response was induced by the orthodontic wire treatment compared to the other models. In addition, pyrosequencing of 16S rRNA gene amplicons revealed that the composition of oral microbiota presented a transition as the disease progressed and significant differences emerged in oral microbiota communities between orthodontic ligature mice and healthy controls. Furthermore, antibiotic treatment decreased both inflammation and alveolar bone loss in response to microbial community dysbiosis. However, no significant difference in bacterial community composition was observed in Pg and Pg-LPS models. Conclusions: Orthodontic wire ligation drove oral microbial community transitions that mimicked polymicrobial communities characterized by polymicrobial synergy and dysbiosis. Our improved model is suitable for further study of pathogenesis of periodontitis and exploration of corresponding treatment strategies.

17.
Ann Palliat Med ; 10(1): 45-60, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33474964

RESUMO

BACKGROUND: Periodontal disease is a chronic inflammatory disease that includes primarily gingivitis and periodontitis, caused by bacterial infection of the supporting structures of the teeth. For years, much attention has been diverted to periodontal disease among the elderly, not enough attention is paid to adolescents. The purpose of this meta-analysis is to evaluate the epidemic trend of periodontal disease in adolescents in mainland China. METHODS: We conducted a comprehensive literature search through PubMed, Embase, CNKI, Chongqing VIP database, Chinese Wan Fang Database, and CBM. A series of subgroup analyses were done to explore the epidemiological characteristics of periodontal disease (gender, location, age, survey year, and geographical distribution) with the help of related software. RESULTS: Thirty studies were included in this study. The data extraction and analysis were from three indexes, including bleeding on probing (BOP), pocket depth (PD), and dental calculus (DC). The detection rates of BOP(+), PD ≥4 mm and DC(+) were 48.8% (95% CI: 36.2-61.4%), 1.0% (0.0-2.0%), and 49.8% (41.0-58.6%), respectively. There were significant differences for the prevalence of gingivitis both in gender and area: the prevalence was higher in males than that in females, and risk ratio was 1.04 (95% CI, 1.01-1.06); a lower prevalence in urban areas compared with rural areas, and the risk ratio was 0.90 (95% CI, 0.85-0.96). CONCLUSIONS: This study shows a high prevalence of gingivitis among adolescents in China. Higher-quality epidemiological surveys with standard examination criteria are needed.


Assuntos
Doenças Periodontais , Adolescente , China/epidemiologia , Feminino , Humanos , Masculino , Doenças Periodontais/epidemiologia , Prevalência , Inquéritos e Questionários
18.
Int J Nanomedicine ; 16: 1405-1422, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33658780

RESUMO

AIM: Iridoid glycosides (IG) as the major active fraction of Syringa oblata Lindl. has a proven anti-inflammatory effect for ulcerative colitis (UC). However, its current commercial formulations are hampered by low bioavailability and unable to reach inflamed colon. To overcome the limitation, dual functional IG-loaded nanoparticles (DFNPs) were prepared to increase the residence time of IG in colon. The protective mechanism of DFNPs on DSS-induced colonic injury was evaluated in rats. MATERIALS AND METHODS: We prepared DFNPs using the oil-in-water emulsion method. PLGA was selected as sustained-release polymer, and ES100 and EL30D-55 as pH-responsive polymers. The morphology and size distribution of NPs were measured by SEM and DLS technique. To evaluate colon targeting of DFNPs, DiR, was encapsulated as a fluorescent probe into NPs. Fluorescent distribution of NPs were investigated. The therapeutic potential and in vivo transportation of NPs in gastrointestinal tract were evaluated in a colitis model. RESULTS: SEM images and zeta data indicated the successful preparation of DFNPs. This formulation exhibited high loading capacity. Drug release results suggested DFNPs released less than 20% at the first 6 h in simulated gastric fluid (pH1.2) and simulated small intestine fluid (pH6.8). A high amount of 84.7% sustained release from NPs in simulated colonic fluid (pH7.4) was beyond 24 h. DiR-loaded NPs demonstrated a much higher colon accumulation, suggesting effective targeting due to functionalization with pH and time-dependent polymers. DFNPs could significantly ameliorate the colonic damage by reducing DAI, macroscopic score, histological damage and cell apoptosis. Our results also proved that the potent anti-inflammatory effect of DFNPs is contributed by decrease of NADPH, gene expression of COX-2 and MMP-9 and the production of TNF-α, IL-17, IL-23 and PGE2. CONCLUSION: We confirm that DFNPs exert protective effects through inhibiting the inflammatory response, which could be developed as a potential colon-targeted system.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Colo/patologia , Glicosídeos Iridoides/uso terapêutico , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ácidos Polimetacrílicos/química , Animais , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Colo/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Sulfato de Dextrana , Liberação Controlada de Fármacos , Fluorescência , Concentração de Íons de Hidrogênio , Glicosídeos Iridoides/sangue , Glicosídeos Iridoides/farmacocinética , Glicosídeos Iridoides/farmacologia , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos ICR , NADPH Oxidases/metabolismo , Nanopartículas/ultraestrutura , Tamanho da Partícula , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Distribuição Tecidual/efeitos dos fármacos
19.
Cell Prolif ; 54(1): e12957, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33231338

RESUMO

BACKGROUND: Periodontitis is a prevalent oral inflammatory disease, which can cause periodontal ligament to a local hypoxia environment. However, the mechanism of hypoxia associated long non-coding RNAs (lncRNAs) involved in periodontitis is still largely unknown. METHODS: Microarray was performed to detect the expression patterns of lncRNAs in 3 pairs of gingival tissues from patients with periodontitis and healthy controls. The expression of lncRNA 01126 (LINC01126), miR-518a-5p and hypoxia-inducible factor-1α (HIF-1α) in periodontal tissues and in human periodontal ligament cells (hPDLCs) under hypoxia was measured by quantitative real-time polymerase chain reaction or western blot. Fluorescence in situ hybridization and cell fraction assay were performed to determine the subcellular localization of LINC01126 and miR-518a-5p. Overexpression or knockdown of LINC01126 or HIF-1α was used to confirm their biological roles in hPDLCs. MTT assays were performed to evaluate hPDLCs proliferation ability. Flow cytometry was used to detect apoptosis. ELISA was used to measure the expression levels of interleukin (IL)-1ß, IL-6, IL-8 and TNF-α. Dual-luciferase reporter assays were performed to assess the binding of miR-518a-5p to LINC01126 and HIF-1α. RNA immunoprecipitation assay was used to identify whether LINC01126 and miR-518a-5p were significantly enriched in AGO-containing micro-ribonucleoprotein complexes. RESULTS: We selected LINC01126, which was the most highly expressed lncRNA, to further verify its functions in periodontitis-induced hypoxia. The expression of LINC01126 was increased in periodontal tissues. In vitro experiment demonstrated that LINC01126 suppressed proliferation, promoted apoptosis and inflammation of hPDLCs under hypoxia via sponging miR-518a-5p. Moreover, we identified HIF-1α acted as a direct target of miR-518a-5p in hPDLCs and LINC01126 promoted periodontitis pathogenesis by regulating the miR-518a-5p/HIF-1α/MAPK pathway. CONCLUSION: LINC01126 promotes periodontitis pathogenesis of hPDLCs via miR-518a-5p/HIF-1α/MAPK pathway, providing a possible clue for LINC01126-based periodontal therapeutic approaches.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , MicroRNAs/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Ligamento Periodontal/metabolismo , Periodontite/metabolismo , RNA Longo não Codificante/metabolismo , Adulto , Apoptose , Proliferação de Células , Feminino , Células HEK293 , Humanos , Hibridização in Situ Fluorescente , Masculino , Ligamento Periodontal/patologia , Periodontite/patologia , RNA Longo não Codificante/genética
20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 41(2): 303-6, 2010 Mar.
Artigo em Zh | MEDLINE | ID: mdl-20506659

RESUMO

OBJECTIVE: To evaluate the stress distribution and offset of dental and periodontal tissues imposed by changes in inner diameter of pulp cavity. METHODS: Six models of maxillary second bicuspid tooth with different inner diameter of pulp cavity were established, including: (1) calcificated pulp without pulp chamberi (2) mostly calcificated pulp chamber with inward reduction of 0. 5 mm in normal pulp cavity; (3) initially calcificated pulp chamber with inward reduction of 0.25 mm in normal pulp cavity; (4) normal pulp cavity; (5) initially absorbed pulp chamber with outward expansion of 0.25 mm in normal pulp cavity; (6) mostly absorbed pulp chamber with outward expansion of 0.5 mm in normal pulp cavity. Vertical and oblique forces with 160 N were loaded on the central fossa, respectively, in order to calculate the stress distribution of dental and periodontal tissues and the maximum incipient offset of the teeth. RESULTS: With loaded vertical and oblique forces on central fossa, increased stress distribution of periodontal tissues and maximum incipient offset of teeth were found in all of the models, which increased with the increase of pulp cavity. CONCLUSION: The change in inner diameter of pulp cavity has an impact on the stress distribution of periodontal tissues and maximum incipient offset of the second upper bicuspid teeth.


Assuntos
Dente Pré-Molar/anatomia & histologia , Dente Pré-Molar/fisiologia , Polpa Dentária/anatomia & histologia , Maxila , Fenômenos Biomecânicos , Análise de Elementos Finitos , Humanos , Estresse Mecânico
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