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Arch Biochem Biophys ; 749: 109788, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37852427


Botulinum toxin A (BoNT-A) has emerged as a treatment option for temporomandibular disorder (TMD). By injecting BoNT-A into the masseter muscle, it is possible to reduce mechanical loading on the temporomandibular joint (TMJ). However, numerous prior studies have indicated excessive reduction in mechanical loading can have detrimental effects on TMJ cartilage. This study proposes that autophagy, a process influenced by mechanical loading, could play a role in BoNT-A-induced mandibular condyle cartilage degeneration. To explore this hypothesis, we employed both BoNT-A injection and an excessive biting model to induce variations in mechanical loading on the condyle cartilage of C57BL/6 mice, thereby simulating an increase and decrease in mechanical loading, respectively. Results showed a significant reduction in cartilage thickness and downregulation of Runt-related transcription factor 2 (Runx2) expression in chondrocytes following BoNT-A injection. In vitro experiments demonstrated that the reduction of Runx2 expression in chondrocytes is associated with autophagy, possibly dependent on decreased YAP expression induced by low mechanical loading. This study reveals the potential involvement of the YAP/LC3/Runx2 signaling pathway in BoNT-A mediated mandibular condylar cartilage degeneration.

Toxinas Botulínicas Tipo A , Cartilagem Articular , Camundongos , Animais , Toxinas Botulínicas Tipo A/metabolismo , Toxinas Botulínicas Tipo A/farmacologia , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/farmacologia , Camundongos Endogâmicos C57BL , Côndilo Mandibular/metabolismo , Condrócitos/metabolismo , Autofagia
Curr Microbiol ; 75(3): 316-322, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29090322


A novel bacterial cells immobilized carrier (ZnONPs/PVA), polyvinyl alcohol (PVA) composites decorated with ZnO nanoparticles (ZnO NPs), was prepared and used for immobilization of the strain Ochrobactrum sp. LC-1, and subsequently for quinoline degrading in water. Characterization of ZnONPs/PVA by using X-ray diffractometer and scanning electron microscopy demonstrated that ZnO NPs were coated on the surface of PVA cubes evenly and the bacterium grew well on the ZnONPs/PVA. Quinoline biodegradation results showed that the degradation effect of quinoline by ZnONPs/PVA immobilized cells was superior to the free cells significantly. The structure and physical properties of ZnNPs/PVA were maintained steady after the reuse of ZnNPs/PVA for cells immobilization several times. Reusability of the ZnONPs/PVA immobilized cells revealed that the quinoline removal ratio was above 97% within 8 h under the conditions of pH neutral, 37 °C when the initial quinoline concentration was 300 mg/L.

Ochrobactrum/química , Ochrobactrum/metabolismo , Quinolinas/metabolismo , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Biodegradação Ambiental , Células Imobilizadas/química , Células Imobilizadas/metabolismo , Nanopartículas/química , Álcool de Polivinil/química , Quinolinas/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/metabolismo , Óxido de Zinco/química
J Periodontol ; 95(3): 268-280, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37515488


BACKGROUND: Inducible nitric oxide synthase (iNOS) is associated with inflammation and osteoclastic differentiation in periodontal disease. This study was conducted to compare the time-dependent variation in iNOS production between the gingiva and other periodontal tissues and to explore the potential association with C-reactive protein (CRP) in early periodontal disease. METHODS: Ligature-induced periodontal disease models (0-14 days) were established in wild-type and CRP knockout rats. Changes in CRP, iNOS, and autophagy levels were examined in the gingiva and other periodontal tissues. Macrophages were treated with lipopolysaccharide and chloroquine to explore the role of autophagy in iNOS production. iNOS, CRP, and autophagy-related proteins were analyzed using Western blotting, immunostaining, and enzyme-linked immunosorbent assays. mRNA expression was detected by quantitative real-time polymerase chain reaction. Hematoxylin and eosin staining was used for histological analysis. Cathepsin K immunostaining and microcomputed tomography of the maxillae were performed to compare alveolar bone resorption. RESULTS: iNOS and CRP levels increased rapidly in periodontal tissues, as observed on Day 2 of ligature, then decreased more rapidly in the gingiva than in other periodontal tissues. CRP deficiency did not prevent iNOS generation, but effectively accelerated iNOS reduction and delayed alveolar bone loss. The CRP effect on iNOS was accompanied by a change in autophagy, which was reduced by CRP knockout. CONCLUSIONS: The regulation of iNOS by CRP shows temporospatial variation in early periodontal disease and is potentially associated with autophagy. These findings may contribute to the early detection and targeted treatment of periodontal disease.

Perda do Osso Alveolar , Proteína C-Reativa , Ratos , Animais , Óxido Nítrico Sintase Tipo II/metabolismo , Proteína C-Reativa/metabolismo , Microtomografia por Raio-X , Perda do Osso Alveolar/patologia , Gengiva/metabolismo , Óxido Nítrico/metabolismo
Adv Sci (Weinh) ; 11(20): e2400916, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38520733


The rigid hull encasing Tartary buckwheat seeds necessitates a laborious dehulling process before flour milling, resulting in considerable nutrient loss. Investigation of lignin composition is pivotal in understanding the structural properties of tartary buckwheat seeds hulls, as lignin is key determinant of rigidity in plant cell walls, thus directly impacting the dehulling process. Here, the lignin composition of seed hulls from 274 Tartary buckwheat accessions is analyzed, unveiling a unique lignin chemotype primarily consisting of G lignin, a common feature in gymnosperms. Furthermore, the hardness of the seed hull showed a strong negative correlation with the S lignin content. Genome-wide detection of selective sweeps uncovered that genes governing the biosynthesis of S lignin, specifically two caffeic acid O-methyltransferases (COMTs) and one ferulate 5-hydroxylases, are selected during domestication. This likely contributed to the increased S lignin content and decreased hardness of seed hulls from more domesticated varieties. Genome-wide association studies identified robust associations between FtCOMT1 and the accumulation of S lignin in seed hull. Transgenic Arabidopsis comt1 plants expressing FtCOMT1 successfully reinstated S lignin content, confirming its conserved function across plant species. These findings provide valuable metabolic and genetic insights for the potential redesign of Tartary buckwheat seed hulls.

Fagopyrum , Lignina , Sementes , Lignina/metabolismo , Lignina/genética , Fagopyrum/genética , Fagopyrum/metabolismo , Sementes/genética , Sementes/metabolismo , Metiltransferases
Ann N Y Acad Sci ; 1485(1): 56-70, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32978798


Mounting evidence indicates that circular RNAs (circRNAs) have essential roles in several diseases, including periodontitis. Periodontal ligament stem cells (PDLSCs) exhibit potential for treating periodontitis accompanied by hypoxia. However, it is unclear how circRNA affects the osteogenesis of PDLSCs under hypoxia. In this study, a novel circRNA, hsa_circ_0003489, was found located at the gene for cyclin-dependent kinase 8 (CDK8) and referred to as circCDK8. The expression levels of circCDK8 and hypoxia-inducible factor-1α were significantly increased in periodontitis tissues, and the expression of circCDK8 was further confirmed in a hypoxia model using cobalt chloride (CoCl2 ). Interestingly, the results showed that the expression levels of osteoblast markers (RUNX2, ALP, OCN, and COL1A1) were increased in CoCl2 -treated PDLSCs at 6 and 12 h, but decreased at 24, 48, and 72 h. On the basis of bioinformatics and functional experiments, CoCl2 also induced endoplasmic reticulum stress, autophagy, and apoptosis of PDLSCs; the inhibition of autophagy promoted the osteogenic differentiation of CoCl2 -treated PDLSCs. Furthermore, circCDK8 overexpression induced autophagy and apoptosis through mTOR signaling, and circCDK8 silencing reversed the inhibitory effects of CoCl2 on osteogenic differentiation of PDLSCs. In conclusion, our results indicate that circCDK8 represses the osteogenic differentiation of PDLSCs by triggering autophagy activation in a hypoxic microenvironment. CircCDK8 could be a new therapeutic target of periodontitis.

Apoptose/fisiologia , Quinase 8 Dependente de Ciclina/genética , Hipóxia/genética , Células-Tronco Mesenquimais/fisiologia , Osteogênese/fisiologia , Ligamento Periodontal/citologia , RNA Circular/genética , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Cobalto/farmacologia , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Quinase 8 Dependente de Ciclina/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/fisiologia , Humanos , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogênese/efeitos dos fármacos , Ligamento Periodontal/efeitos dos fármacos , Periodontite/genética , Periodontite/metabolismo , RNA Circular/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
Arch Oral Biol ; 118: 104863, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32818884


OBJECTIVE: The aim of this study was to identify candidate genes and gene sets associated with dental caries by an integrative analysis of transcriptome-wide association study (TWAS) and messenger RNA (mRNA) expression profiling of dental caries. METHODS: A genome-wide association study (GWAS) dataset of dental caries was obtained from the UK Biobank. A TWAS of dental caries was conducted with the FUSION tool using the gene expression reference weights of musculoskeletal, whole blood, and peripheral blood genes. The dental caries-associated genes identified by the TWAS were further subjected to gene ontology (GO) and pathway enrichment analyses to explore dental caries-related gene sets. Finally, the TWAS results of dental caries were compared with genome-wide mRNA expression profiling of dental caries to detect common genes and gene sets. RESULTS: The TWAS identified 165 musculoskeletal genes, 110 whole blood genes, and 228 peripheral blood genes. GO analysis of the genes identified by the TWAS detected 57 GO terms. For pathway enrichment analysis, we detected 12 candidate pathways. After comparing the TWAS-identified genes with the mRNA expression profiling data, we detected 6 common genes. Further comparing the GO results of the TWAS and mRNA expression profiling identified 5 common GO terms. CONCLUSION: We identified a group of dental caries-associated genes and GO terms, providing novel clues for understanding the genetic mechanisms of dental caries.

Cárie Dentária/genética , Estudo de Associação Genômica Ampla , Transcriptoma , Perfilação da Expressão Gênica , Ontologia Genética , Predisposição Genética para Doença , Humanos , RNA Mensageiro/genética