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Overexpression of carboxyl/cholinesterase (CCE) genes has been reported to be associated with many cases of pesticide resistance in arthropods. However, it has been rarely documented that CCE genes participate in spirodiclofen resistance in Panonychus citri. In previous research, we found that spirodiclofen resistance is related to increased P450 and CCE enzyme activities in P. citri. In this study, we identified two CCE genes, PcCCE3 and PcCCE5, which were significantly upregulated in spirodiclofen-resistant strain and after exposure to spirodiclofen. RNA interference of PcCCE3 and PcCCE5 increased the spirodiclofen susceptibility in P. citri. In vitro metabolism indicated that PcCCE3 and PcCCE5 could interact with spirodiclofen, but metabolites were detected only in the PcCCE3 treatment. Our results indicated that PcCCE3 participates in spirodiclofen resistance through direct metabolism, and PcCCE5 may be involved in the spirodiclofen resistance by passive binding and sequestration, which provides new insights into spirodiclofen resistance in P. citri.
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Proteínas de Artrópodes , Compostos de Espiro , Animais , Compostos de Espiro/farmacologia , Compostos de Espiro/metabolismo , Compostos de Espiro/química , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/metabolismo , Proteínas de Artrópodes/química , Resistência a Medicamentos/genética , Carboxilesterase/genética , Carboxilesterase/metabolismo , 4-Butirolactona/análogos & derivados , 4-Butirolactona/metabolismo , 4-Butirolactona/farmacologiaRESUMO
Insecticide susceptibility is mainly determined by the insect host, but symbiotic bacteria are also an important affecting factor. In this study, we investigate the relationship between the structure of gut bacterial symbionts and insecticide susceptibility in Diaphorina citri, the important carrier of Candidatus Liberibacter asiaticus (CLas), the causal agent of Huanglongbing (HLB). Our results indicated that antibiotic treatment significantly increased the susceptibility of D. citri to bifenthrin and thiamethoxam, and significantly decreased the relative abundance of Wolbachia and Profftella, enzyme activities of CarEs, and expression level of multiple CarE genes. The relative loads of Wolbachia and Profftella were positively correlated with DcitCCE13, DcitCCE14, DcitCCE15, and DcitCCE16. RNAi and prokaryotic expression revealed that DcitCCE15 is associated with bifenthrin metabolism. These results revealed that bacterial symbionts might regulate DcitCCE15 expression, which is involved in the susceptibility of D. citri to bifenthrin.
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Hemípteros , Inseticidas , Simbiose , Animais , Inseticidas/farmacologia , Hemípteros/microbiologia , Hemípteros/genética , Hemípteros/efeitos dos fármacos , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Resistência a Inseticidas/genética , Wolbachia/efeitos dos fármacos , Wolbachia/genética , Piretrinas/farmacologia , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , Inativação Metabólica/genéticaRESUMO
Chronic skin wounds are a serious complication of diabetes with a high incidence rate, which can lead to disability or even death. Previous studies have shown that mesenchymal stem cells derived extracellular vesicles (EVs) have beneficial effects on wound healing. However, the human foreskin mesenchymal stem cell (FSMSCs)-derived extracellular vesicle (FM-EV) has not yet been isolated and characterized. Furthermore, the limited supply and short lifespan of EVs also hinder their practical use. In this study, we developed an injectable dual-physical cross-linking hydrogel (PSiW) with self-healing, adhesive, and antibacterial properties, using polyvinylpyrrolidone and silicotungstic acid to load FM-EV. The EVs were evenly distributed in the hydrogel and continuously released. In vivo and vitro tests demonstrated that the synergistic effect of EVs and hydrogel could significantly promote the repair of diabetic wounds by regulating macrophage polarization, promoting angiogenesis, and improving the microenvironment. Overall, the obtained EVs-loaded hydrogels developed in this work exhibited promising applicability for the repair of chronic skin wounds in diabetes patients.
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Vesículas Extracelulares , Prepúcio do Pênis , Hidrogéis , Células-Tronco Mesenquimais , Cicatrização , Hidrogéis/administração & dosagem , Hidrogéis/química , Humanos , Cicatrização/efeitos dos fármacos , Animais , Masculino , Prepúcio do Pênis/citologia , Pele/lesões , Pele/metabolismo , Diabetes Mellitus Experimental/complicações , Camundongos , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , InjeçõesRESUMO
BACKGROUND: Studies have proved that low albumin level is associated with increased mortality in most diseases, such as chronic kidney disease and hepatic cirrhosis. However, the relationship between albumin and all-cause death in heart failure patients in China is still unclear. OBJECTIVES: We aimed to investigate the association between albumin level and 28-day mortality in Chinese hospitalized patients with NYHA IV heart failure. METHODS: A total of 2008 Chinese patients were included. The correlation between serum albumin level and mortality was tested using a cox proportional hazards regression model. The smooth curve fitting was used to identify non-linear relationships between serum albumin and mortality. The Forest plot analysis was used to assess the association between albumin and 28-day mortality in different groups. RESULTS: Compared with patients with NYHA II-III, patients with NYHA IV had lower albumin level and higher mortality within 28 days. The albumin on admission was independently and inversely associated with the endpoint risk, which remained significant (hazard ratio: 0.80; 95 % confidence interval: 0.66 to 0.96; p = 0.0196) after multivariable adjustment. The smooth curve fitting showed with the increase of albumin, the mortality within 28 days would decrease. A subgroup analysis found that the inverse association between the albumin level and risk of the mortality was consistent across the subgroup stratified by possible influence factors. CONCLUSION: Serum albumin level is negatively associated with 28-day mortality in hospitalized heart failure patients within NYHA IV in China, which can be used as an independent predictor.
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Insuficiência Cardíaca , Albumina Sérica , Humanos , Prognóstico , Causas de Morte , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Oxidative stress indicators affect chronic orofacial pain (COFP), but how to reduce these effects is uncertain. OBJECTIVES: 11 oxidative stress biomarkers were collected as exposures, while four forms of COFP were chosen as outcomes for Mendelian randomization (MR) study. METHODS: The effect estimates between oxidative stress and COFP were calculated using inverse variance-weighted MR (IVW-MR). Then, functional mapping and annotation (FUMA) was utilized in order to carry out SNP-based functional enrichment analyses. In addition, the IVW-MR method was applied to combine effect estimates when using genetic variants associated with oxidative stress biomarkers as an instrument for exploring potential druggable targets. RESULTS: The results indicated that oxidative stress biomarkers (causal OR of uric acid (UA), 0.998 for myofascial pain, 95% CI 0.996-1.000, p < .05; and OR of glutathione transferase (GST), 1.002 for dentoalveolar pain, 95% CI 1.000-1.003, p < .05) were significantly linked with the probability of COFP. Functional analysis also demonstrated that UA and myofascial pain genes were prominent in nitrogen and uracil metabolism, while GST and dentoalveolar pain genes were enriched in glutathione metabolism. Also, the study provided evidence that solute carrier family 2 member 9 (SLC2A9) and glutathione S-transferase alpha 2 (GSTA2) cause discomfort in the myofascial pain (OR = 1.003, 95% CI 1.000-1.006; p < .05) and dentoalveolar region (OR = 1.001, 95% CI 1.000-1.002; p < .05), respectively. CONCLUSIONS: In conclusion, this MR study indicates that genetically predicted myofascial pain was significantly associated with decreased UA and dentoalveolar pain was significantly associated with increased GST level. SLC2A9 inhibitor and GSTA2 inhibitor were novel chronic orofacial pain therapies and biomarkers, but clinical trials are called to examine if these oxidative biomarkers have the protective effect against orofacial pain, and further research are needed to explore the underlying mechanisms.
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Biomarcadores , Dor Crônica , Dor Facial , Análise da Randomização Mendeliana , Estresse Oxidativo , Polimorfismo de Nucleotídeo Único , Humanos , Dor Facial/genética , Dor Facial/fisiopatologia , Dor Crônica/genética , Dor Crônica/metabolismo , Glutationa Transferase/genética , Ácido Úrico/sangueRESUMO
The effects of Easydo Activator (EA), a new sonic irrigation system, on sealer penetration at the root apex were compared to needle irrigation (NI) and passive ultrasonic irrigation (PUI) in this study. Forty-two single-rooted teeth were prepared and randomly divided into three groups (n = 14): group 1: NI; group 2: PUI; and group 3: EA. A solution of 3% sodium hypochlorite (NaOCl) was used for irrigation. Nine teeth in each group were filled with AH Plus sealer mixed with CY5 fluorescent dye and a single gutta-percha cone. The sealer penetration area, maximum penetration depth and percentage of sealer penetration at 5 mm and 1 mm from the apex were analyzed by confocal laser scanning microscopy (CLSM). The remaining 5 teeth in each group were subjected to test smear layer scores by scanning electron microscopy (SEM). The CLSM evaluation showed that increases in the area, depth and percentage of sealer penetration were detected at 1 and 5 mm from the root apex in the PUI group compared with the NI group, and greater increases were observed in the EA group (P < 0.05). The SEM experiment showed that the lowest scores for the smear layer and debris removal were achieved by the EA group when compared with the PUI and NI groups (P < 0.05). In conclusion, EA was superior to PUI and NI regarding sealer penetration at the root apex during endodontic treatment, and it could provide a new technical idea for clinical root canal therapy.
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Camada de Esfregaço , Humanos , Assistência Odontológica , Guta-Percha , Microscopia Confocal , UltrassomRESUMO
Melanoma is a melanocyte-derived malignant cancer and is known for its early metastasis and high mortality rates. It is a highly cutaneous tumour disease that could be related to the abnormal immune microenvironment, and the identification of reliable diagnostic and prognostic markers is crucial for improving patient outcomes. In the search for biomarkers, various types of RNAs have been discovered and recognized as reliable prognostic markers. Among these, small nucleolar RNAs (snoRNAs) have emerged as a promising avenue for studying early diagnosis and prognostic markers in tumours due to their widespread presence in tissues, tumour specificity and stability. In our study, we analysed snoRNAs data from melanoma samples in the TCGA-SKCM cohort and developed a prognostic model comprising 12 snoRNAs (SNORD9, SNORA31, SNORD14E, SNORA14A, SNORA5A, SNORD83A, SNORA75, AL096855, AC007684, SNORD14A, SNORA65 and AC004839). This model exhibited unique prognostic accuracy and demonstrated a significant correlation with the immune infiltration tumour microenvironment. Additionally, analysis of the GSE213145 dataset, which explored the sensitivity and resistance of immune checkpoint inhibitors, further supported the potential of snoRNAs as prognostic markers for immunotherapy. Overall, our study contributes reliable prognostic and immune-related biomarkers for melanoma patients. These findings can offer valuable insights for the future discovery of novel melanoma treatment strategies and hold promise for improving clinical outcomes in melanoma patients.
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Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/genética , RNA Nucleolar Pequeno/genética , Prognóstico , Neoplasias Cutâneas/genética , Biomarcadores , Microambiente TumoralRESUMO
Cell death is a fundamental physiological process in all living organisms. Processes such as embryonic development, organ formation, tissue growth, organismal immunity, and drug response are accompanied by cell death. In recent years with the development of electron microscopy as well as biological techniques, especially the discovery of novel death modes such as ferroptosis, cuprotosis, alkaliptosis, oxeiptosis, and disulfidptosis, researchers have been promoted to have a deeper understanding of cell death modes. In this systematic review, we examined the current understanding of modes of cell death, including the recently discovered novel death modes. Our analysis highlights the common and unique pathways of these death modes, as well as their impact on surrounding cells and the organism as a whole. Our aim was to provide a comprehensive overview of the current state of research on cell death, with a focus on identifying gaps in our knowledge and opportunities for future investigation. We also presented a new insight for macroscopic intracellular survival patterns, namely that intracellular molecular homeostasis is central to the balance of different cell death modes, and this viewpoint can be well justified by the signaling crosstalk of different death modes. These concepts can facilitate the future research about cell death in clinical diagnosis, drug development, and therapeutic modalities.
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Background: The coronavirus disease 2019 (COVID-19) caused a global pandemic, with potential severity. We aimed to investigate whether genetically predicted gut microbiome is associated with susceptibility and severity of COVID-19 risk. Methods: Mendelian randomization (MR) analysis of two sets with different significance thresholds was carried out to infer the causal relationship between the gut microbiome and COVID-19. SNPs associated with the composition of the gut microbiome (n = 5,717,754) and with COVID-19 susceptibility (n = 14,328,058), COVID-19 severity (n = 11,707,239), and COVID-19 hospitalization (n = 12,018,444) from publicly available genome-wide association studies (GWAS). The random-effect inverse variance weighted (IVW) method was used to determine causality. Three more MR techniques-MR Egger, weighted median, and weighted mode-and a thorough sensitivity analysis were also used to confirm the findings. Results: IVW showed that 18 known microbial taxa were causally associated with COVID-19. Among them, six microbial taxa were causally associated with COVID-19 susceptibility; seven microbial taxa were causally associated with COVID-19 severity ; five microbial taxa were causally associated with COVID-19 hospitalization. Sensitivity analyses showed no evidence of pleiotropy or heterogeneity. Then, the predicted 37 species of the gut microbiome deserve further study. Conclusion: This study found that some microbial taxa were protective factors or risky factors for COVID-19, which may provide helpful biomarkers for asymptomatic diagnosis and potential therapeutic targets for COVID-19.
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COVID-19 , Microbioma Gastrointestinal , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , COVID-19/genética , CausalidadeRESUMO
Kangfuxin (KFX) shows potential in wound healing, but its role in socket healing is unclear. This research finds increased bone mass, mineralization, and collagen deposition in KFX-treated mice. Mouse bone marrow mesenchymal stem cells, human periodontal ligament stem cells (hPDLSCs), and human dental pulp stem cells (hDPSCs) are treated with KFX under osteogenic induction. RNA-sequencing reveals upregulated chemokine-related genes, with a threefold increase in chemokine (C-C motif) ligand 2 (Ccl2). The conditioned medium (CM) of hPDLSCs and hDPSCs treated with KFX promotes endothelial cell migration and angiogenesis. Ccl2 knockdown abolishes CM-induced endothelial cell migration and angiogenesis, which can be reversed by recombinant CCL2 treatment. KFX-treated mice showed increased vasculature. In conclusion, KFX increases the expression of CCL2 in stem cells, promoting bone formation and mineralization in the extraction socket by inducing endothelial cell angiogenesis. © 2023 American Society for Bone and Mineral Research (ASBMR).
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Quimiocina CCL2 , Ligamento Periodontal , Humanos , Animais , Camundongos , Ligamento Periodontal/metabolismo , Regulação para Cima , Quimiocina CCL2/metabolismo , Células-Tronco/metabolismo , Cicatrização , Osteogênese/fisiologia , Diferenciação Celular/fisiologiaRESUMO
BACKGROUND: Jaw-bone defects caused by various diseases lead to aesthetic and functional complications, which can seriously affect the life quality of patients. Current treatments cannot fully meet the needs of reconstruction of jaw-bone defects. Thus, the research and application of bone tissue engineering are a "hot topic." As seed cells for engineering of jaw-bone tissue, oral cavity-derived stem cells have been explored and used widely. Models of jaw-bone defect are excellent tools for the study of bone defect repair in vivo. Different types of bone defect repair require different stem cells and bone defect models. This review aimed to better understand the research status of oral and maxillofacial bone regeneration. MAIN TEXT: Data were gathered from PubMed searches and references from relevant studies using the search phrases "bone" AND ("PDLSC" OR "DPSC" OR "SCAP" OR "GMSC" OR "SHED" OR "DFSC" OR "ABMSC" OR "TGPC"); ("jaw" OR "alveolar") AND "bone defect." We screened studies that focus on "bone formation of oral cavity-derived stem cells" and "jaw bone defect models," and reviewed the advantages and disadvantages of oral cavity-derived stem cells and preclinical model of jaw-bone defect models. CONCLUSION: The type of cell and animal model should be selected according to the specific research purpose and disease type. This review can provide a foundation for the selection of oral cavity-derived stem cells and defect models in tissue engineering of the jaw bone.
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Osso e Ossos , Engenharia Tecidual , Animais , Células-Tronco , Osteogênese , Regeneração Óssea , BocaRESUMO
BACKGROUND: The Oral Health-related Quality of Life (OHRQoL) is a multi-dimensional concept commonly used to examine the impact of health status on quality of life, and the Oral Health Impact Profile-14 (OHIP-14) questionnaire is a good self-assessment tool. This study was designed to investigate the factor structure of the OHIP-14 scale Chinese version, measurement invariance and latent mean differences across genders among college students. METHODS: The online survey was completed by 919 college students. This study used confirmatory factor analysis (CFA) to check the structural models of the OHIP-14 scale, The correlation of each item with the scale total score could test homogeneity, and Cronbach's alpha (Cronbach's α) could evaluate internal consistency. Multi-group CFA was used to explore whether the Chinese version of the OHIP-14 scale was used in male and female populations for measurement consistency. T-test compared scores between men and women. Regression analyses were used to evaluate the relationship between age, gender, education, subject, and the score on the OHIP-14 scale. RESULTS: We found that the 7-factor structure had the best fit index in the sample. According to Cronbach's α, the overall score of OHIP was 0.958, and Cronbach's α for 7 factors was: functional limitation was 0.800, physical pain was 0.854, psychological discomfort was 0.902, physical disability was 0.850, psychological disability was 0.768, social disability was 0.862, social handicap was 0.819 and the test-retest reliability interval was 0.723. Multi-group confirmatory factor analysis supported residual measurement invariance across gender. T-test for scores showed that females scored higher significantly than men as did the overall score, in terms of physical pain (p<0.001), physical disability (p<0.001), and psychological disability (p<0.001). CONCLUSIONS: This study found the OHIP-14 Chinese version to be a good tool for assessing the college students' OHRQoL in China, allowing people to conduct self-assessments.
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Saúde Bucal , Qualidade de Vida , Feminino , Humanos , Masculino , Dor , Reprodutibilidade dos Testes , Estudantes , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: To evaluate the long-term therapeutic effect of EASYDO ACTIVATOR, passive ultrasonic irrigation, and needle irrigation in experimental apical periodontitis in rats. MATERIALS AND METHODS: Sprague-Dawley male rats were used to produce periapical lesions. The pulp chambers of the bilaterally first mandibular molars were exposed and left open for 21 days. The rats were divided into four groups according to different irrigation protocols. Seven days after irrigation, the mandibles were removed for micro-CT, histological, and immunohistochemical analysis. Serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were assessed by enzyme-linked immunosorbent assays (ELISA). Statistical data were analyzed by one-way analysis of variance (ANOVA) with LSD tests. RESULTS: The passive ultrasonic irrigation and EASYDO ACTIVATOR groups had the smallest apical lesions compared to the other groups (P < 0.05), while the needle irrigation group had smaller lesions than the control group (P < 0.05). The EASYDO ACTIVATOR group had less inflammation infiltration compared to the control and needle irrigation groups (P < 0.05). The control and needle irrigation groups had more TNF-α expression compared to the passive ultrasonic irrigation and EASYDO ACTIVATOR groups (P < 0.05). The lowest IL-6 expression was observed in the EASYDO ACTIVATOR group. The EASYDO ACTIVATOR group had the lowest serum level of TNF-α than other groups (P < 0.05). IL-6 expression was significantly lower in the EASYDO ACTIVATOR group in comparison with the control and needle irrigation groups (P < 0.05). CONCLUSIONS: EASYDO ACTIVATOR can significantly reduce the apical lesions and decrease the inflammatory response around the periapical area. CLINICAL RELEVANCE: EASYDO ACTIVATOR is recommended for clinical application.
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Periodontite Periapical , Ultrassom , Animais , Masculino , Ratos , Cavidade Pulpar , Interleucina-6 , Periodontite Periapical/terapia , Ratos Sprague-Dawley , Irrigantes do Canal Radicular , Preparo de Canal Radicular/métodos , Irrigação Terapêutica/métodos , Fator de Necrose Tumoral alfaRESUMO
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease. Not only genetics, but the intestinal environment affected by gut microbiota is also the key to pathogenesis. Besides the occurrence of diabetes, gut microbiota dysbiosis may also contribute to the development of diabetes-related complications. Fecal microbiota transplantation (FMT) is an emerging technique that had shown its potential as a treatment for metabolic disease. Here, we report the first case of T1DM with malnutrition and gastrointestinal symptoms treated with FMT. A 24-year-old T1DM patient suffered from poor blood glucose control, recurrent nausea and vomiting, severe malnutrition, and intractable constipation after insulin treatment. The clinical response of the patients after FMT was well, especially nausea and vomiting were significantly relieved. In addition, constipation, nutritional status, and blood glucose control (fasting blood glucose, HbA1c) gradually improved. A degree of similarity was found in gut microbiota composition between the patient and healthy donor after FMT while it was totally different before the treatment. Furthermore, pathway function analysis of MetaCYC database implies that the potential mechanism of the response of FMT may be driven by specific bacteria involved in several metabolic pathways that need further exploration. To sum up, we believe that the reconstruction of intestinal flora by FMT may be a new choice for the treatment of T1DM patients with malnutrition.
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Bone tissue engineering (BTE) is a promising method for the repair of difficult-to-heal bone tissue damage by providing three-dimensional structures for cell attachment, proliferation, and differentiation. Traditional Chinese medicine (TCM) has been introduced as an effective global medical program by the World Health Organization, comprising intricate components, and promoting bone regeneration by regulating multiple mechanisms and targets. This study outlines the potential therapeutic capabilities of TCM combined with BTE in bone regeneration. The effective active components promoting bone regeneration can be generally divided into flavonoids, alkaloids, glycosides, terpenoids, and polyphenols, among others. The chemical structures of the monomers, their sources, efficacy, and mechanisms are described. We summarize the use of compounds and medicinal parts of TCM to stimulate bone regeneration. Finally, the limitations and prospects of applying TCM in BTE are introduced, providing a direction for further development of novel and potential TCM.
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The immunological response occurring during periapical inflammation includes expression of nucleotide binding oligomerization domain containing 2 and hepcidin. Nucleotide binding oligomerization domain containing 2 deficiency increases infiltration of inflammatory cells close to alveolar bone. Hepcidin has an important role in iron metabolism affecting bone metabolism.We investigated the role of nucleotide binding oligomerization domain containing 2 and hepcidin in inflammatory periapical periodontitis. Periapical periodontitis was induced in rats and confirmed by micro-computed tomography. Nucleotide binding oligomerization domain 2 and hepcidin were evaluated through immunohistochemistry. Bioinformatics analysis was undertaken usingthe Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases. Micro-computer tomography revealed alveolar bone resorption in the periapical region and furcation area of mandibular molars in rats of the periapical periodontitis group. Immunohistochemistry showed increased expressionof nucleotide binding oligomerization domain containing 2 and hepcidin around root apices in rats of the periapical periodontitis group. Bioinformatics analysis of differentially expressed genes in inflamed and non-inflamed tissues revealed enrichment in the NOD-like receptor signaling pathway. Our data suggest that nucleotide binding oligomization domain contain2 and hepcidin have important roles in periapical periodontitis severity because they can reduce alveolar bone loss.They could elicit new perspectives for development of novel strategies for periapical periodontitis treatment.
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Hepcidinas , Proteína Adaptadora de Sinalização NOD2 , Periodontite Periapical , Perda do Osso Alveolar/genética , Perda do Osso Alveolar/metabolismo , Perda do Osso Alveolar/patologia , Animais , Hepcidinas/genética , Hepcidinas/metabolismo , Proteína Adaptadora de Sinalização NOD2/genética , Proteína Adaptadora de Sinalização NOD2/metabolismo , Nucleotídeos/metabolismo , Periodontite Periapical/genética , Periodontite Periapical/metabolismo , Periodontite Periapical/patologia , Ratos , Microtomografia por Raio-XRESUMO
BACKGROUND: Bone formation and loss are the characteristic clinical manifestations of leprosy, but the mechanisms underlying the bone remodeling with Mycobacterium leprae (M. leprae) infection are unclear. METHODOLOGY/PRINCIPAL FINDINGS: Osteocytes may have a role through regulating the differentiation of osteogenic lineages. To investigate osteocyte-related mechanisms in leprosy, we treated osteocyte-like cell with N-glycosylated muramyl dipeptide (N.g MDP). RNA-seq analysis showed 724 differentially expressed messenger RNAs (mRNAs) and 724 differentially expressed circular RNA (circRNAs). Of these, we filtered through eight osteogenic-related differentially expressed genes, according to the characteristic of competing endogenous RNA, PubMed databases, and bioinformatic analysis, including TargetScan, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. Based on these results, we built a circRNA-microRNA (miRNA)-mRNA triple network. Quantitative reverse-transcription polymerase chain reaction and western blots analyses confirmed decreased Clock expression in osteocyte-like cell, while increased in bone mesenchymal stem cells (BMSCs), implicating a crucial factor in osteogenic differentiation. Immunohistochemistry showed obviously increased expression of CLOCK protein in BMSCs and osteoblasts in N.g MDP-treated mice, but decreased expression in osteocytes. CONCLUSIONS/SIGNIFICANCE: This analytical method provided a basis for the relationship between N.g MDP and remodeling in osteocytes, and the circRNA-miRNA-mRNA triple network may offer a new target for leprosy therapeutics.
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Hanseníase , MicroRNAs , Animais , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Mycobacterium leprae/genética , Mycobacterium leprae/metabolismo , Osteócitos/metabolismo , Osteogênese/genética , RNA Circular/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Periodontitis is a globally prevalent disease that imposes a functional and aesthetic burden on patients. The oral microbiome influences human health. The aim of this study was at assessing gender variation in the subgingival bacterial microbiome of elderly patients with initial periodontitis and to determine the causes of this variation. Twelve males and twenty females (range 50-68 years old) with initial periodontitis provided subgingival plaque samples. 16S rRNA gene sequencing, QIIME-based data processing, and statistical analyses were carried out using several different analytical approaches to detect differences in the oral microbiome between the two groups. Males had higher Chao1 index, observed species, and phylogenetic diversity whole tree values than females. Analysis of ß-diversity indicated that the samples were reasonably divided by the gender. The linear discriminant analysis effect size showed that the most representative biomarkers were the genus Haemophilus in males, whereas the dominant bacteria in females were Campylobacter. Kyoto Encyclopedia of Genes and Genomes analysis showed that predicting changes in the female oral microbiota may be related to the immune system and immune system diseases are the main factor in males. These data suggest that gender may be a differentiating factor in the microbial composition of subgingival plaques in elderly patients with initial periodontitis. These results could deepen our understanding of the role of gender in the oral microbiota present during initial periodontitis.
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Campylobacter/fisiologia , Haemophilus/fisiologia , Periodontite/epidemiologia , RNA Ribossômico 16S/genética , Fatores Sexuais , Idoso , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Microbiota/genética , Pessoa de Meia-Idade , Boca , Periodontite/microbiologia , Caracteres SexuaisRESUMO
OBJECTIVE: Periodontitis is an inflammatory disease of microbial etiology caused primarily by dysbiosis of the oral microbiota. Our aim was to compare variations in the composition of the oral microbiomes of youths with severe periodontitis according to gender. METHODS: Subgingival plaque samples collected from 17 patients with severe periodontitis (11 males and 6 females) were split for 16S rRNA gene sequencing. The composition, α-diversity, and ß-diversity of the patients' oral microbiomes were compared between the males and the females. Linear discriminant analysis effect size (LEfSe) was used to analyze the specific taxa enriched in the two groups. Functional profiles (KEGG pathways) were obtained using PICRUSt based on 16S rRNA gene sequencing data. RESULTS: The Chao1 index and phylogenetic diversity whole tree were significantly higher in males than in females. The Simpson and Shannon indices were not significantly different between the two groups. ß-Diversity suggested that the samples were reasonably divided into groups. The Kruskal-Wallis test based on the relative abundance of species, combined with the LEfSe analysis showed that the dominant bacteria in males were Pseudomonas and Papillibacter, whereas the dominant bacteria in women were Fusobacteriales and Tannerella. KEGG analysis predicted that the variation in the oral microbiome may be related to the immune system in women, whereas immune system diseases were the dominant pathway in men. CONCLUSION: We found sex-specific differences in the oral microbiome in a sample of youths with severe periodontitis. The differences may be related to changes in immune homeostasis and lead to a better understanding of periodontitis.
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Disbiose/diagnóstico , Microbiota/imunologia , Mucosa Bucal/microbiologia , Periodontite/microbiologia , Adulto , DNA Bacteriano/isolamento & purificação , Disbiose/complicações , Disbiose/imunologia , Disbiose/microbiologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Microbiota/genética , Periodontite/diagnóstico , Periodontite/imunologia , Filogenia , RNA Ribossômico 16S/genética , Índice de Gravidade de Doença , Fatores SexuaisRESUMO
Human exposure to drinking water disinfection by-products (DBPs) is potentially linked to high blood pressure (BP), which may be associated with abnormal platelet activation. This study investigated whether the relationship between DBP exposure with platelet change was mediated by BP. DBP biomarkers, such as urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), BP and platelet indices from 505 adults from a hospital in Shijiazhuang, China were measured. The cross-sectional associations among DCAA and TCAA exposure, BP and platelet indices were explored through multivariable linear regressions, and the mediation effect of BP was evaluated using the Sobel-Goodman test. We observed that DCAA and TCAA were positively associated with systolic BP (all p for trends < 0.01), which was positively associated with platelet count (PLC) (p for trend < 0.05). Mediation analysis indicated that systolic BP fully mediated the associations of DCAA and TCAA with PLC. When BP was controlled, a previously inverse significant relation between DCAA and platelet distribution width (PDW) remained significant (p < 0.05). Obtained results suggested that exposure to DCAA may contribute to decreased PDW in humans. Systolic BP is a possible mediator of the association between DCAA exposure and PLC. TCAA may indirectly positively affect PLC by increasing systolic BP.