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Glioblastoma stem cells (GSCs) exert a crucial influence on glioblastoma (GBM) development, progression, resistance to therapy, and recurrence, making them an attractive target for drug discovery. UTX, a histone H3K27 demethylase, participates in regulating multiple cancer types. However, its functional role in GSCs remains insufficiently explored. This study aims to investigate the role and regulatory mechanism of UTX on GSCs. Analysis of TCGA data revealed heightened UTX expression in glioma, inversely correlating with overall survival. Inhibiting UTX suppressed GBM cell growth and induced apoptosis. Subsequently, we cultured primary GSCs from three patients, observing that UTX inhibition suppressed cell proliferation and induced apoptosis. RNA-seq was performed to analyze the gene expression changes after silencing UTX in GSCs. The results indicated that UTX-mediated genes were strongly correlated with GBM progression and regulatory tumor microenvironment. The transwell co-cultured experiment showed that silencing UTX in the transwell chamber GSCs inhibited the well plate cell proliferation. Protein-protein interaction analysis revealed that periostin (POSTN) played a role in the UTX-mediated transcriptional regulatory network. Replenishing POSTN reversed the effects of UTX inhibition on GSC proliferation and apoptosis. Our study demonstrated that UTX inhibition hindered POSTN expression by enhancing the H3K27me2/3 level, eventually resulting in inhibiting proliferation and promoting apoptosis of patient-derived GSCs. Our findings may provide a novel and effective strategy for the treatment of GBM.
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Neoplasias Encefálicas , Glioblastoma , Histona Desmetilases , Células-Tronco Neoplásicas , Humanos , Apoptose/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/patologia , Células-Tronco Neoplásicas/patologia , Periostina , Microambiente Tumoral , Histona Desmetilases/antagonistas & inibidores , Histona Desmetilases/metabolismoRESUMO
BACKGROUND: Root caries are prevalent issues that affect dental health, particularly among elderly individuals with exposed root surfaces. Fluoride therapy has shown effectiveness in preventing root caries, but limited studies have addressed its cost-effectiveness in elderly persons population. This study aimed to evaluate the cost-effectiveness of a fluoride treatment program for preventing root caries in elderly persons within the context of Chinese public healthcare. METHODS: A Markov simulation model was adopted for the cost-effectiveness analysis in a hypothetical scenario from a healthcare system perspective. A 60-year-old subject with 23 teeth was simulated for 20 years. A 5% sodium fluoride varnish treatment was compared with no preventive intervention in terms of effectiveness and cost. Tooth years free of root caries were set as the effect. Transition probabilities were estimated from the data of a community-based cohort and published studies, and costs were based on documents published by the government. The incremental cost-effectiveness ratio (ICER) was calculated to evaluate cost-effectiveness. Univariate and probabilistic sensitivity analyses were performed to evaluate the influence of data uncertainty. RESULTS: Fluoride treatment was more effective (with a difference of 10.20 root caries-free tooth years) but also more costly (with a difference of ¥1636.22). The ICER was ¥160.35 per root caries-free tooth year gained. One-way sensitivity analysis showed that the risk ratio of root caries in the fluoride treatment group influenced the result most. In the probabilistic sensitivity analysis, fluoride treatment was cost-effective in 70.5% of the simulated cases. CONCLUSIONS: Regular 5% sodium fluoride varnish application was cost-effective for preventing root caries in the elderly persons in most scenarios with the consideration of data uncertainty, but to a limited extent. Improved public dental health awareness may reduce the incremental cost and make the intervention more cost-effective. Overall, the study shed light on the economic viability and impact of such preventive interventions, providing a scientific basis for dental care policies and healthcare resource allocation.
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Cariostáticos , Fluoretos Tópicos , Cárie Radicular , Fluoreto de Sódio , Idoso , Humanos , Pessoa de Meia-Idade , Cariostáticos/economia , Cariostáticos/uso terapêutico , China , Análise de Custo-Efetividade , Fluoretos Tópicos/uso terapêutico , Fluoretos Tópicos/economia , Cadeias de Markov , Cárie Radicular/prevenção & controle , Cárie Radicular/economia , Fluoreto de Sódio/economia , Fluoreto de Sódio/uso terapêuticoRESUMO
OBJECTIVE: To compare the personalities, social avoidance and distress, and anxiety status of Chinese patients with and without objective halitosis, and investigate the association among these psychological disorders. METHODS: Patients who complained of bad breath and diagnosed with objective halitosis were enrolled into the halitosis group, while patients without objective halitosis were enrolled into the control group. The questionnaires included the sociodemographic profile of the participants, Eysenck Personality Questionnaire (EPQ), Social Avoidance and Distress Scale (SAD), and Beck Anxiety Inventory (BAI). RESULTS: A total of 280 patients were assigned into objective halitosis group (n = 146) and control group (n = 134). The extraversion subscales (E) score of the EPQ in the halitosis group were significantly lower than that in the control group (p = 0.001). The total SAD score and proportion of patients with anxiety symptoms in the BAI scale in the objective halitosis was significantly higher than that in the control group (p < 0.05). There was a negative correlation between the extraversion subscale and the total SAD score, Social Avoidance and Social Distress subscales (p < 0.001). CONCLUSION: Patients with objective halitosis have more introverted personality traits and are more likely to have social avoidance and distress than the nonhalitosis population.
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Anesthetics such as sevoflurane are commonly administered to infants and children. However, the possible neurotoxicity caused by prolonged or repetitive exposure to it should be a concern. The neuroprotective effects of metformin are observed in many models of neurological disorders. In this study, we investigated whether metformin could reduce the developmental neurotoxicity induced by sevoflurane exposure in neonatal rats and the potential mechanism. Postnatal day 7 (PND 7) Sprague-Dawley rats and neural stem cells (NSCs) were treated with normal saline or metformin before sevoflurane exposure. The Morris water maze (MWM) was used to observe spatial memory and learning at PND 35-42. Immunofluorescence staining was used to detect neurogenesis in the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus at PND 14. MTT assays, immunofluorescence staining, and TUNEL staining were used to assess the viability, proliferation, differentiation, and apoptosis of NSCs. Western blotting and ELISA were used to assess the protein expression of cleaved caspase-3, nuclear factor erythroid 2-related factor 2 (Nrf2), and glucose-6-phosphate dehydrogenase (G6PD) pathway-related molecules. Exposure to sevoflurane resulted in late cognitive defects, impaired neurogenesis in both the SVZ and SGZ, reduced NSC viability and proliferation, increased NSC apoptosis, and decreased protein expression of G6PD in vitro. Metformin pretreatment attenuated sevoflurane-induced cognitive functional decline and neurogenesis inhibition. Metformin pretreatment also increased the protein expression of Nrf2 and G6PD. However, treatment with the Nrf2 inhibitor, ML385 or the G6PD inhibitor, dehydroepiandrosterone (DHEA) reversed the protective effect of metformin on sevoflurane-induced NSC damage in vitro. Our findings suggested that metformin could reduce sevoflurane-induced neurogenesis damage and neurocognitive defects in the developing rat brain by influencing the Nrf2/G6PD signaling pathways.
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Disfunção Cognitiva , Fator 2 Relacionado a NF-E2 , Animais , Ratos , Sevoflurano/farmacologia , Ratos Sprague-Dawley , Fator 2 Relacionado a NF-E2/metabolismo , Animais Recém-Nascidos , Glucosefosfato Desidrogenase/efeitos adversos , Glucosefosfato Desidrogenase/metabolismo , Neurogênese , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Hipocampo/metabolismoRESUMO
Therapeutic strategies based on neural stem cells (NSCs) transplantation bring new hope for neural degenerative disorders, while the biological behaviors of NSCs after being grafted that were affected by the host tissue are still largely unknown. In this study, we engrafted NSCs that were isolated from a rat embryonic cerebral cortex onto organotypic brain slices to examine the interaction between grafts and the host tissue both in normal and pathological conditions, including oxygen-glucose deprivation (OGD) and traumatic injury. Our data showed that the survival and differentiation of NSCs were strongly influenced by the microenvironment of the host tissue. Enhanced neuronal differentiation was observed in normal conditions, while significantly more glial differentiation was observed in injured brain slices. The process growth of grafted NSCs was guided by the cytoarchitecture of host brain slices and showed the distinct difference between the cerebral cortex, corpus callosum and striatum. These findings provided a powerful resource for unraveling how the host environment determines the fate of grafted NSCs, and raise the prospect of NSCs transplantation therapy for neurological diseases.
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Células-Tronco Neurais , Ratos , Animais , Encéfalo , Diferenciação Celular/fisiologia , Córtex Cerebral , Corpo Estriado , Transplante de Células-Tronco/métodosRESUMO
Neural stem cells (NSCs) persist in the subgranular zone (SGZ) throughout the lifespan and hold immense potential for the repair and regeneration of the central nervous system, including hippocampal-related diseases. Several studies have demonstrated that cellular communication network protein 3 (CCN3) regulates multiple types of stem cells. However, the role of CCN3 in NSCs remains unknown. In this study, we identified CCN3 expression in mouse hippocampal NSCs and observed that supplementing CCN3 improved cell viability in a concentration-dependent manner. Additionally, in vivo results showed that the injection of CCN3 in the dentate gyrus (DG) increased Ki-67- and SOX2-positive cells while decreasing neuron-specific class III beta-tubulin (Tuj1) and doublecortin (DCX)-positive cells. Consistently with the in vivo results, supplementing CCN3 in the medium increased the number of BrdU and Ki-67 cells and the proliferation index but decreased the number of Tuj1 and DCX cells. Conversely, both the in vivo and in vitro knockdown of the Ccn3 gene in NSCs had opposite effects. Further investigations revealed that CCN3 promoted cleaved Notch1 (NICD) expression, leading to the suppression of PTEN expression and eventual promotion of AKT activation. In contrast, Ccn3 knockdown inhibited the activation of the Notch/PTEN/AKT pathway. Finally, the effects of changes in CCN3 protein expression on NSC proliferation and differentiation were eliminated by FLI-06 (a Notch inhibitor) and VO-OH (a PTEN inhibitor). Our findings imply that while promoting proliferation, CCN3 inhibits the neuronal differentiation of mouse hippocampal NSCs and that the Notch/PTEN/AKT pathway may be a potential intracellular target of CCN3. Our findings may help develop strategies to enhance the intrinsic potential for brain regeneration after injuries, particularly stem cell treatment for hippocampal-related diseases.
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Proteína Sobre-Expressa em Nefroblastoma , Células-Tronco Neurais , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Diferenciação Celular , Proliferação de Células , Hipocampo/metabolismo , Antígeno Ki-67/metabolismo , Proteína Sobre-Expressa em Nefroblastoma/metabolismo , Células-Tronco Neurais/metabolismo , Neurogênese/genética , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
3-hydroxybutyrate (3OHB) has been proved to act as a neuroprotective molecule in multiple neurodegenerative diseases. Here, we employed a quantitative proteomics approach to assess the changes of the global protein expression pattern of neural cells upon 3OHB administration. In combination with a disease-related, protein-protein interaction network we pinpointed a hub marker, histone lysine 27 trimethylation, which is one of the key epigenetic markers in multiple neurodegenerative diseases. Integrative analysis of transcriptomic and epigenomic datasets highlighted the involvement of bivalent transcription factors in 3OHB-mediated disease protection and its alteration of neuronal development processes. Transcriptomic profiling revealed that 3OHB impaired the fate decision process of neural precursor cells by repressing differentiation and promoting proliferation. Our study provides a new mechanism of 3OHB's neuroprotective effect, in which chromatin bivalency is sensitive to 3OHB alteration and drives its neuroprotective function both in neurodegenerative diseases and in neural development processes.
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Células-Tronco Neurais , Fármacos Neuroprotetores , Cromatina/genética , Ácido 3-Hidroxibutírico , Proteoma , Fármacos Neuroprotetores/farmacologia , HidroxibutiratosRESUMO
The potential of neural stem cells (NSCs) for neurological disorders the treatment has relied in large part upon identifying the NSCs fate decision. The hormone leptin has been reported to be a crucial regulator of brain development, able to influence the glial and neural development, yet, the underlying mechanism of leptin acting on NSCs' biological characteristics is still poorly understood. This study aims to investigate the role of leptin in the biological properties of NSCs. In this study, we investigate the possibility that leptin may regulate the NSCs' fate decision, which may promote the proliferation and neuronal differentiation of NSCs and thus act positively in neurological disorders. NSCs from the embryonic cerebral cortex were used in this study. We used CCK-8 assay, ki67 immunostaining, and FACS analysis to confirm that 25-100 ng/mL leptin promotes the proliferation of NSCs in a concentration-dependent pattern. This change was accompanied by the upregulation of p-AKT and p-ERK1/2, which are the classical downstream signaling pathways of leptin receptors b (LepRb). Inhibition of PI3K/AKT or MAPK/ERK signaling pathways both abolished the effect of leptin-induced proliferation. Moreover, leptin also enhanced the directed neuronal differentiation of NSCs. A blockade of the PI3K/AKT pathway reversed leptin-stimulated neurogenesis, while a blockade of JAK2/STAT3 had no effect on it. Taken together, our results support a role for leptin in regulating the fate of NSCs differentiation and promoting NSCs proliferation, which could be a promising approach for brain repair via regulating the biological characteristics of NSCs.
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Doenças do Sistema Nervoso , Células-Tronco Neurais , Humanos , Sistema de Sinalização das MAP Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Leptina/farmacologia , Leptina/metabolismo , Proliferação de Células , Transdução de Sinais , Células-Tronco Neurais/metabolismo , Diferenciação Celular , Doenças do Sistema Nervoso/metabolismo , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismoRESUMO
Traumatic brain injury is a leading cause of neuroinflammation and anxiety disorders in young adults. Immune-targeted therapies have garnered attention for the amelioration of TBI-induced anxiety. A previous study has indicated that voluntary exercise intervention following TBI could reduce neuroinflammation. It is essential to determine the effects of voluntary exercise after TBI on anxiety via inhibiting neuroinflammatory response. Mice were randomly divided into four groups (sham, TBI, sham + voluntary wheel running (VWR), and TBI + VWR). One-week VWR was carried out on the 2nd day after trauma. The neurofunction of TBI mice was assessed. Following VWR, anxiety behavior was evaluated, and neuroinflammatory responses in the perilesional cortex were investigated. Results showed that after one week of VWR, neurofunctional recovery was enhanced, while the anxiety behavior of TBI mice was significantly alleviated. The level of pro-inflammatory factors decreased, and the level of anti-inflammatory factors elevated. Activation of nucleotide oligomerization domain-like thermal receptor protein domain associated protein 3 (NLRP3) inflammasome was inhibited significantly. All these alterations were consistent with reduced microglial activation at the perilesional site and positively correlated with the amelioration of anxiety behavior. This suggested that timely rehabilitative exercise could be a useful therapeutic strategy for anxiety resulting from TBI by targeting neuroinflammation.
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Lesões Encefálicas Traumáticas , Atividade Motora , Camundongos , Animais , Doenças Neuroinflamatórias , Encéfalo/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Inflamação/tratamento farmacológico , Ansiedade/etiologia , Ansiedade/terapia , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Electrolyzed water (EW) is recognized as an effective way to control and reduce pathogens in vegetables. However, the disinfection efficacy of EW alone is limited. In this work, the bactericidal activity and biofilm removal capability of EW, generated by adding NaCl to a portable EW generator, were investigated with special reference to Listeria monocytogenes. Furthermore, the impact of EW in combination with dimethyl dicarbonate (DMDC) in reducing the microbial load and improving the overall quality of lettuce during refrigerated storage was evaluated. RESULTS: EW with 0.3% NaCl (SEW) had the highest bactericidal activity against L. monocytogenes. The pathogen treated with SEW exhibited lower superoxide dismutase activity and more leakage of proteins and nucleic acids than in the case of EW. Furthermore, the use of SEW resulted in changes in the cell permeability and morphology of L. monocytogenes. A decrease in adhesion and collapse of the biofilm architecture were also observed, indicating that SEW was more effective for inactivating L. monocytogenes cells compared to EW. For untreated lettuce, the populations of the total plate count and inoculated L. monocytogenes decreased by 2.47 and 2.35 log CFU g-1 , respectively, after the combined SEW/DMDC treatment for 3 min. The use of SEW alone or combined with DMDC did not negatively impact the lettuce color values, titratable acid, ascorbic acid and soluble solids compared to the control group. CONCLUSION: SEW in combination with DMDC can be used as a novel and potentially effective disinfection strategy for ensuring the safety of vegetable consumption. © 2023 Society of Chemical Industry.
Assuntos
Desinfetantes , Listeria monocytogenes , Lactuca , Água/farmacologia , Cloreto de Sódio/farmacologia , Desinfetantes/farmacologia , Microbiologia de Alimentos , Eletrólise , Contagem de Colônia Microbiana , VerdurasRESUMO
BACKGROUND: We aimed to investigate the association between oral health and cognitive function in a sample of older adults from a Chinese rural community. METHODS: The cross-sectional cognitive function of 677 individuals were assessed by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). A comprehensive profile of the oral health status was evaluated by questionnaire and clinical examination. RESULTS: Multiple covariates-adjusted regression models demonstrated decayed teeth (DT) and decayed/missing/filled teeth (DMFT) were negatively associated with MoCA score (all p < 0.05). Calculus index (CI) and clinical attachment loss (CAL) were significantly associated with the lower MoCA, short-term memory and executive function score, respectively (all p < 0.05). Additionally, participants with missing teeth unrestored tend to get lower MMSE and MoCA scores (p < 0.05). The results also showed that increased DT and CI were modestly associated with higher odds of cognitive impairment (p < 0.05). CONCLUSIONS: There is an association between oral health and global cognition. Poor periodontal status was strongly associated with worse global cognition performance, especially in the short-term memory and executive domain for the aging population.
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Anodontia , Disfunção Cognitiva , Humanos , Idoso , Saúde Bucal , Estudos Transversais , População do Leste Asiático , CogniçãoRESUMO
Excess salt intake harms the brain health and cognitive functions, but whether a maternal high-salt diet (HSD) affects the brain development and neural plasticity of offspring remains unclear. Here, using a range of behavioral tests, we reported that the offspring of maternal HSD subjects exhibited short- and long-term memory deficits, especially in spatial memory in adulthood. Moreover, impairments in synaptic transmission and plasticity in the hippocampus were observed in adult offspring by using in vivo electrophysiology. Consistently, the number of astrocytes but not neurons in the hippocampus of the offspring from the HSD group were significantly decreased, and ERK and AKT signaling pathways involved in neurodevelopment were highly activated only during juvenile. In addition, the expression of synaptic proteins decreased both in juvenile and adulthood, and this effect might be involved in synaptic dysfunction. Collectively, these data demonstrated that the maternal HSD might cause adult offspring synaptic dysfunction and memory loss. It is possibly due to the reduction of astrocytes in juvenile.
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Memória/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Cloreto de Sódio na Dieta/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , GravidezRESUMO
OBJECTIVES: To assess the effects of periodontitis on renal interstitial fibrosis in a mouse model. MATERIALS AND METHODS: Thirty C57BL/6 male mice were divided into control, periodontitis (PD), unilateral ureteral ligation (UUO) and PD+UUO groups. Unilateral ureteral ligation was performed 6 days after periodontitis. After 2 weeks, all mice were sacrificed, and samples were collected for the assessment of gene expression, immune cells, biochemical indicators and renal pathology. RESULTS: Expression of tumour necrosis factor-α, interleukin-1ß, and Ly6G in the kidneys in the PD+UUO group was significantly greater than in the UUO group. The percentage of CD11b+ Ly6G+ cells was significantly higher in the PD+UUO than in the UUO group. Fibrotic areas in the kidneys in the PD+UUO group were slightly, but not significantly, greater than those in the UUO group. Kidneys from the PD+UUO group showed markedly higher gene expression of matrix metalloproteinase-9, but not α-smooth muscle actin or collagen I, than those in the UUO group. There were no significant differences in blood urea nitrogen, serum creatinine and uric acid between the PD+UUO and UUO groups. CONCLUSIONS: Periodontitis increases the renal inflammatory response without showing a significant influence on renal interstitial fibrosis or renal function in the UUO mouse model.
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Periodontite , Obstrução Ureteral , Animais , Modelos Animais de Doenças , Fibrose , Rim/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Periodontite/metabolismo , Obstrução Ureteral/genética , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologiaRESUMO
OBJECTIVES: To investigate the correlation between serum and gingival crevicular fluid (GCF) levels of inflammatory cytokines and the association with periodontal parameters in patients with maintenance hemodialysis (MHD) and healthy control. MATERIALS AND METHODS: Patients who were undergoing MHD were enrolled as the MHD group. Healthy individuals who underwent oral examination were selected as the control group after matching for the MHD group. All participants underwent a full-mouth periodontal evaluation, and the levels of eight inflammatory cytokines, including IL-1ß, IL-17, IL-6, IL-8, and tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-8 (MMP-8), and C-reactive protein (CRP), in the GCF and serum were measured. RESULTS: A total of 63 MHD patients and 75 healthy persons were included. The prevalence of moderate/severe periodontitis was significantly higher in the MHD group than in the control group (88.9 vs. 66.7%, P < 0.05). The GCF levels of CRP, TNF-α, MCP-1, and MMP-8 were higher in patients in the MHD group with moderate/severe periodontitis than in the control group (P < 0.05). Serum CRP, MCP-1, TNF-α, and MMP-8 levels were positively correlated with the GCF CRP levels (P < 0.05). The GCF and serum CRP levels were positively correlated with the periodontal clinical parameters (P < 0.05). CONCLUSIONS: Serum CRP, MCP-1, TNF-α, and MMP-8 may relate with the GCF CRP levels. The GCF and serum CRP levels correlated positively with the periodontal clinical parameters, including the VPI, PPD, and CAL, indicating that CRP may play an important role between periodontitis and ESRD. CLINICAL RELEVANCE: The present study indicated that GCF and serum CRP levels correlated positively with the periodontal clinical parameters, and the CRP levels may be selected as an indicator to evaluate the severity of inflammation and the effectiveness, prognosis of periodontal treatment in ESRD patients.
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Periodontite Crônica , Falência Renal Crônica , Humanos , Periodontite Crônica/terapia , Metaloproteinase 8 da Matriz , Citocinas , Fator de Necrose Tumoral alfa/análise , Líquido do Sulco Gengival/química , Proteína C-Reativa/análise , Diálise Renal , Falência Renal Crônica/terapiaRESUMO
Neural stem/progenitor cells (NSPCs) persist in the mammalian subventricular zone throughout life, where they can be activated in response to physiological and pathophysiological stimuli. A recent study indicates metabotropic glutamate receptor 4 (mGluR4) is involved in regulating NSPCs behaviors. Therefore, defining mGluR4 function in NSPCs is necessary for determining novel strategies to enhance the intrinsic potential for brain regeneration after injuries. In this study, mGluR4 was functionally expressed in SVZ-derived NSPCs from male Sprague-Dawley rats, in which the cyclic adenosine monophosphate concentration was reduced after treatment with the mGluR4-specific agonist VU0155041. Additionally, lateral ventricle injection of VU0155041 significantly decreased 5-bromo-2'-deoxyuridine (BrdU)+ and Ki67+ cells, while increased Doublecortin (DCX)/BrdU double-positive cells in SVZ. In cultured NSPCs, mGluR4 activation decreased the ratio of BrdU+ cells, G2/M-phase cells, and inhibited Cyclin D1 expression, whereas it increased neuron-specific class III ß-tubulin (Tuj1) expression and the number of Tuj1, DCX, and PSA-NCAM-positive cells. However, pharmacological blocking mGluR4 with the antagonist MSOP or knockdown of mGluR4 abolished the effects of VU0155041 on NSPCs proliferation and neuronal differentiation. Further investigation demonstrated that VU0155041 treatment down-regulated AKT phosphorylation and up-regulated expression of the phosphatase and tensin homolog protein (PTEN) in NSPCs culture. Moreover VU0155041-induced proliferating inhibition and neuronal differentiating amplification in NSPCs were significantly hampered by VO-OHpic, a PTEN inhibitor. We conclude that activation of mGluR4 in SVZ-derived NSPCs suppresses proliferation and enhances their neuronal differentiation, and regulation of PTEN may be involved as a potential intracellular target of mGluR4 signal. Cover Image for this issue: https://doi.org/10.1111/jnc.15052.
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Diferenciação Celular/fisiologia , Ventrículos Laterais/metabolismo , Células-Tronco Neurais/metabolismo , PTEN Fosfo-Hidrolase/biossíntese , Receptores de Glutamato Metabotrópico/metabolismo , Anilidas/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Ácidos Cicloexanocarboxílicos/farmacologia , Relação Dose-Resposta a Droga , Proteína Duplacortina , Expressão Gênica , Ventrículos Laterais/citologia , Ventrículos Laterais/efeitos dos fármacos , Masculino , Células-Tronco Neurais/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Neurogênese/fisiologia , PTEN Fosfo-Hidrolase/genética , Ratos , Ratos Sprague-Dawley , Receptores de Glutamato Metabotrópico/agonistasRESUMO
OBJECTIVES: To compare the prevalence of chronic periodontitis between men who had semen abnormalities and those who had normozoospermia through a case-control study. MATERIALS AND METHODS: Male patients who visited the assisted reproduction clinic of a large general hospital and were diagnosed with semen abnormalities were included in the case group. The control group was composed of patients of the same clinic with normozoospermia. The semen analysis included sperm concentration, count and progressive and total motility, which were measured in the laboratory. A questionnaire and clinical periodontal examination were conducted for all participants. Logistic regression was performed to explore the relationship between chronic periodontitis and male infertility. RESULTS: A total of 192 participants were included: 63 participants (32.8%) had some type of semen abnormality (case group), while 129 participants (67.2%) had normozoospermia (control group). The case group had a significantly higher prevalence of moderate/severe periodontitis than the control group (33.3% vs. 17.8%, p = .012). The logistic regression showed that participants who had moderate/severe periodontitis had a greater chance of having semen abnormalities after adjusting for other confounding factors (OR = 3.377, p = .005). CONCLUSIONS: Periodontitis is associated with semen abnormalities and sperm motility in men.
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Infertilidade Masculina , Doenças Periodontais , Estudos de Casos e Controles , Humanos , Infertilidade Masculina/epidemiologia , Masculino , Contagem de Espermatozoides , Motilidade dos EspermatozoidesRESUMO
BACKGROUND: This study aimed to explore the trend and risk indicators for dental caries of children aged 12 years in China based on national oral health survey data in 2005 and 2015. METHODS: Research data were from the two latest national oral health surveys conducted in mainland China, including 30 and 31 provinces, autonomous regions, and municipalities in 2005 and 2015, respectively. Children aged 12 years were clinically examined for dental caries and dental fluorosis according to the World Health Organization criteria. Sociodemographic characteristics and oral health-related behaviours were collected using questionnaires. Multilevel zero-inflated negative binomial regression model was used to investigate the association between dental caries severity and dental fluorosis, sociodemographic characteristics, and oral health-related behaviours. RESULTS: The final analyses included 12,350 and 27,818 children surveyed in 2005 and 2015, respectively. The standardized prevalence of dental caries increased from 27.05% (95% confidence interval [CI], 24.25-28.85) in 2005 to 37.92% (95% CI, 34.94-40.90) in 2015, and the respective standardized mean decayed, missing, filled teeth (DMFT) index scores increased from 0.50 (standard deviation [SD], 1.04) to 0.83 (SD, 1.45) (P < 0.001). Fujian province had the highest increase in dental caries, followed by Liaoning, Heilongjiang, Hainan, and Yunnan. Results revealed that children who were girls, more frequently experienced dental pain, and had more recent dental visits, had significantly higher DMFT scores after adjusting for the survey year and other variables (all P < 0.05). CONCLUSIONS: Dental caries of 12-year-old children in China deteriorated from 2005 to 2015, particularly in the northeast and southwest regions. Dental caries was associated with sex, dental pain, and dental service utilization.
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Cárie Dentária , Criança , China/epidemiologia , Estudos Transversais , Índice CPO , Cárie Dentária/epidemiologia , Feminino , Humanos , Análise Multinível , PrevalênciaRESUMO
The activation of microglia in response to intracerebral hemorrhagic stroke is one of the principal components of the progression of this disease. It results in the formation of pro-inflammatory cytokines that lead to neuronal death, a structural deterioration that, in turn interferes with functional recovery. Metabotropic glutamate receptor 5 (mGluR5) is highly expressed in reactive microglia and is involved in the pathological processes of brain disorders, but its role in intracerebral hemorrhage (ICH) remains unknown. We hypothesized that mGluR5 regulates microglial activation and ICH maintenance. In this study, collagenase-induced ICH mice received a single intraperitoneal injection of the mGluR5 antagonist-, MTEP, or vehicle 2 h after injury. We found that acute ICH upregulated mGluR5 and microglial activation. mGluR5 was highly localized in reactive microglia in the peri-hematomal cortex and striatum on days 3 and 7 post-ICH. The MTEP-mediated pharmacological inhibition of mGluR5 in vivo resulted in the substantial attenuation of acute microglial activation and IL-6, and TNF-α release. We also showed that the blockade of mGluR5 markedly reduced cell apoptosis, and neurodegeneration and markedly elevated neuroprotection. Furthermore, the MTEP-mediated inhibition of mGluR5 significantly reduced the lesion volume and improved functional recovery. Taken together, our results demonstrate that ICH injury enhances mGluR5 expression in the acute and subacute stages and that mGluR5 is highly localized in reactive microglia. The blockade of mGluR5 reduces ICH-induced acute microglial activation, provides neuroprotection and promotes neurofunctional recovery after ICH. The inhibition of mGluR5 may be a relevant therapeutic target for intracerebral hemorrhagic stroke.
Assuntos
Hemorragia Cerebral/prevenção & controle , Microglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Piridinas/uso terapêutico , Receptor de Glutamato Metabotrópico 5/antagonistas & inibidores , Tiazóis/uso terapêutico , Animais , Morte Celular , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patologia , Masculino , Camundongos , Microglia/metabolismo , Microglia/patologia , Neurônios/metabolismo , Neurônios/patologia , Piridinas/farmacologia , Distribuição Aleatória , Receptor de Glutamato Metabotrópico 5/metabolismo , Tiazóis/farmacologiaRESUMO
Thermal conductivity measurements for organic molecules are difficult and time-consuming. In this study, the thermal conduction of liquid aldehydes and ketones was simulated using nonequilibrium molecular dynamics, and the thermal conductivity at different temperatures was calculated. The deviation between the calculated values and the experimental data of thermal conductivity is less than 4.86%. By decomposing the heat flux, we found that thermal energy is primarily transferred through the torsion angle, angle bending, Coulomb interaction, and kinetic energy in the liquid state. Moreover, as the molecular chain grows, the thermal energy transmitted through the nonbonded interaction decreases, and the thermal energy transmitted through the intramolecular bonded interaction increases, which indicates a significant relationship between the mechanism of heat transfer and the molecular structure. Using molecular dynamics simulation, this research offers a preliminary understanding of the contributions of microscopic heat transfer to the thermal conductivities of liquid aldehydes and ketones.
Assuntos
Temperatura Alta , Simulação de Dinâmica Molecular , Aldeídos , Cetonas , Condutividade TérmicaRESUMO
OBJECTIVE: The present case-control study aimed to compare the psychological status of patients with and without halitosis, and investigate the association between psychological disorders and halitosis. METHODS: Patients who complained about bad breath and diagnosed with genuine halitosis were assigned to the halitosis group, while patients without genuine halitosis were assigned to the control group (n = 106, each group). Information on the demographics and Symptom Checklist-90 (SCL-90) of participants was collected. The organoleptic score and Halimeter measurement were used to measure halitosis. RESULTS: The mean SCL-90 score of participants in the halitosis group (0.63) was significantly greater than that in the control group (0.48) (p = .002). The scores of the domains of interpersonal sensitivity, anxiety, depression, and paranoid ideation were found to be significantly different between the two groups (p < .05). However, there were no significant differences in SCL-90 scores between the mild and moderate-severe halitosis groups (p = .479). CONCLUSION: The psychological status of genuine halitosis patients was significantly worse than normal patients without halitosis complaint and also without halitosis. The main problems were in the aspects of interpersonal sensitivity, anxiety, depression, and paranoia. However, the negative impact was not related to the severity of halitosis.