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AIMS: This study aimed to elucidate the alterations in Follistatin-like protein 1 (FSTL1) and its association with the pathological process of periodontitis. METHODS: This study included 48 patients with periodontitis and 42 healthy controls. The expression level of FSTL1 in the gingiva was determined by RT-qPCR, validated using the dataset GSE16134, and subsequently examined by western blotting. Bioinformatics analysis revealed a single-cell distribution of FSTL1, characteristic of angiogenesis and immune cell infiltration. The expression and distribution of FSTL1, vascular endothelial marker protein CD31 and myeloperoxidase (MPO), the indicator of neutrophil activity, were determined by immunohistochemistry (IHC). A series of correlation analyses was performed to determine the associations between FSTL1 and clinical parameters, including probing depth (PD) and clinical attachment loss (CAL), and their potential role in angiogenesis (CD31) and neutrophil infiltration (MPO). RESULTS: FSTL1 was significantly upregulated in the gingiva of patients with periodontitis compared to their healthy counterparts. In addition, FSTL1 was positively correlated with the clinical parameters PD (r = .5971, p = .0005) and CAL (r = .6078, p = .0004). Bioinformatic analysis and IHC indicated that high FSTL1 expression was significantly correlated with angiogenesis and neutrophil infiltration in periodontitis. Moreover, receiver operating characteristic (ROC) analysis demonstrated that FSTL1 could serve as an independent indicator for evaluating the severity of periodontitis (area under the curve [AUC] = 0.9011, p < .0001). CONCLUSION: This study demonstrated FSTL1 upregulation in periodontitis and its potential contribution to the disease via angiogenesis and neutrophil infiltration.
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BACKGROUND: The reduced treatment time of dental implants with immediate loading protocol is an appealing solution for dentists and patients. However, there remains a significant risk of early peri-implant bone response following the placement of immediately loaded implants, and limited information is available regarding loading directions and the associated in vivo characteristics of peri-implant bone during the early stages. This study aimed to investigate the effects of immediate loading directionality on the expression of mechanical sensing protein PIEZO1 and the healing process of peri-implant bone in the early stage. METHODS: Thirty-two implants were inserted into the goat iliac crest models with 10 N static lateral immediate loading applied, followed by histological, histomorphological, immunohistochemical, X-ray microscopy and energy dispersive X-ray spectroscopy evaluations conducted after 10 days. RESULTS: From evaluations at the cellular, tissue, and organ levels, it was observed that the expression of mechanical sensing protein PIEZO1 in peri-implant bone was significantly higher in the compressive side compared to the tensile side. This finding coincided with trends observed in interfacial bone extracellular matrix (ECM) contact percentage, bone mass, and new bone formation. CONCLUSIONS: This study provides a novel insight into the immediate loading directionality as a potential influence factor for dental implant treatments by demonstrating differential effects on the mechanical sensing protein PIEZO1 expression and related early-stage healing processes of peri-implant bone. Immediate loading directions serve as potential therapeutic influence factors for peri-implant bone during its early healing stage.
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Implantes Dentales , Cicatrización de Heridas , Humanos , Prótesis e Implantes , Canales IónicosRESUMEN
OBJECTIVE: The USA has higher rates of fatal motor vehicle collisions than most high-income countries. Previous studies examining the role of the built environment were generally limited to small geographic areas or single cities. This study aims to quantify associations between built environment characteristics and traffic collisions in the USA. METHODS: Built environment characteristics were derived from Google Street View images and summarised at the census tract level. Fatal traffic collisions were obtained from the 2019-2021 Fatality Analysis Reporting System. Fatal and non-fatal traffic collisions in Washington DC were obtained from the District Department of Transportation. Adjusted Poisson regression models examined whether built environment characteristics are related to motor vehicle collisions in the USA, controlling for census tract sociodemographic characteristics. RESULTS: Census tracts in the highest tertile of sidewalks, single-lane roads, streetlights and street greenness had 70%, 50%, 30% and 26% fewer fatal vehicle collisions compared with those in the lowest tertile. Street greenness and single-lane roads were associated with 37% and 38% fewer pedestrian-involved and cyclist-involved fatal collisions. Analyses with fatal and non-fatal collisions in Washington DC found streetlights and stop signs were associated with fewer pedestrians and cyclists-involved vehicle collisions while road construction had an adverse association. CONCLUSION: This study demonstrates the utility of using data algorithms that can automatically analyse street segments to create indicators of the built environment to enhance understanding of large-scale patterns and inform interventions to decrease road traffic injuries and fatalities.
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BACKGROUND: Entirely impacted mandibular third molar (EIM3M) concerns the pathological external root resorption (ERR) of the adjacent mandibular second molar (M2M) and formation of granulation tissue between two molars. The study aimed to clarify the effect of αENaC, a mechano-sensitive molecule, to explore the mechanical mechanism in this scenario. METHODS: The force EIM3M exerted on M2M was proved by finite element analysis. αENaC expressions were tested by real-time polymerase chain reaction (PCR), immunoblotting and immunofluorescence. Inflammatory and epithelial-mesenchymal transition (EMT)-related molecules expressions were also detected by real-time PCR. The correlation was analyzed by Spearman's correlation analysis, and receiver-operator characteristic (ROC) curve was further exhibited. RESULTS: The force was concentrated in the ERR area. αENaC was upregulated, positively correlated with ERR degree and localized to the fibroblasts in ERR granulation tissues. Moreover, αENaC was respectively and positively associated with elevated TNF-α and N-cadherin in ERR granulation tissues. More importantly, ROC analysis verified αENaC as a novel indication of the incidence of this disease. CONCLUSIONS: Our finding revealed the force from EIM3M causing ERR of M2M, and elucidated the expression and localization of αENaC and its positive correlation with inflammation, EMT and disease severity, suggesting a novel indication in this disease.
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Resorción Radicular , Diente Impactado , Humanos , Resorción Radicular/etiología , Tercer Molar , Tomografía Computarizada de Haz Cónico , Diente MolarRESUMEN
BACKGROUND: Mechanosensitive ion channel PIEZOs have been widely reported to involve inflammation and pain. This study aimed to clarify expression patterns of PIEZOs and their potential relations to irreversible pulpitis. MATERIALS AND METHODS: Normal pulp tissues (n = 29) from patients with impacted third molars and inflamed pulp tissues (n = 23) from patients with irreversible pulpitis were collected. Pain levels were assessed using a numerical rating scale. PIEZO expressions were measured using real-time PCR and then confirmed using GEO datasets GSE77459, immunoblot, and immunohistochemistry staining. Correlations of PIEZO mRNA expression with inflammatory markers, pain markers, or clinical pain levels were evaluated using Spearman's correlation analysis. Univariate analysis was conducted to analyze PIEZO expressions based on pain description and clinical examinations of cold test, percussion, palpation, and bite test. RESULTS: Compared with normal pulp tissues, mRNA expression levels of PIEZO1 were significantly increased in inflamed pulp tissues, while PIEZO2 was significantly decreased, which was further confirmed in GSE77459 and on a protein and histological level. The positive correlation of the mRNA expression levels between PIEZO1 and inflammatory markers, as well as between PIEZO2 and pain markers, was verified. PIEZO2 expression was also positively correlated with pain levels. Besides, irreversible pulpitis patients who reported continuous pain and who detected a positive response to cold stimulus exhibited a higher expression level of PIEZO2 in the inflamed pulp tissues. By contrast, patients reporting pain duration of more than one week showed a higher expression level of PIEZO1. CONCLUSIONS: This study demonstrated the upregulation of PIEZO1 and the downregulation of PIEZO2 in irreversible pulpitis and revealed the potential relation of PIEZO1 and PIEZO2 to inflammation and pain. These findings suggested that PIEZOs might play critical roles in the progression of irreversible pulpitis and paved the way for further investigations aimed at novel therapies of irreversible pulpitis by targeting PIEZOs.
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Pulpitis , Humanos , Canales Iónicos/genética , Canales Iónicos/metabolismo , Inflamación , Dolor , ARN MensajeroRESUMEN
BACKGROUND AND OBJECTIVE: Periodontitis is a multifactorial chronic inflammatory disease that can lead to the irreversible destruction of dental support tissues. As an epigenetic factor, the expression of circRNA is tissue-dependent and disease-dependent. This study aimed to identify novel periodontitis-associated circRNAs and predict relevant circRNA-periodontitis regulatory network by using recently developed bioinformatic tools and integrating sequencing profiling with clinical information for getting a better and more thorough image of periodontitis pathogenesis, from gene to clinic. MATERIAL AND METHODS: High-throughput sequencing and RT-qPCR were conducted to identify differentially expressed circRNAs in gingival tissues from periodontitis patients. The relationship between upregulated circRNAs expression and probing depth (PD) was performed using Spearman's correlation analysis. Bioinformatic analyses including GO analysis, circRNA-disease association prediction, and circRNA-miRNA-mRNA network prediction were performed to clarify potential regulatory functions of identified circRNAs in periodontitis. A receiver-operating characteristic (ROC) curve was established to assess the diagnostic significance of identified circRNAs. RESULTS: High-throughput sequencing identified 70 differentially expressed circRNAs (68 upregulated and 2 downregulated circRNAs) in human periodontitis (fold change >2.0 and p < .05). The top five upregulated circRNAs were validated by RT-qPCR that had strong associations with multiple human diseases, including periodontitis. The upregulation of circRNAs were positively correlated with PD (R = .40-.69, p < .05, moderate). A circRNA-miRNA-mRNA network with the top five upregulated circRNAs, differentially expressed mRNAs, and overlapped predicted miRNAs indicated potential roles of circRNAs in immune response, cell apoptosis, migration, adhesion, and reaction to oxidative stress. The ROC curve showed that circRNAs had potential value in periodontitis diagnosis (AUC = 0.7321-0.8667, p < .05). CONCLUSION: CircRNA-disease associations were predicted by online bioinformatic tools. Positive correlation between upregulated circRNAs, circPTP4A2, chr22:23101560-23135351+, circARHGEF28, circBARD1 and circRASA2, and PD suggested function of circRNAs in periodontitis. Network prediction further focused on downstream targets regulated by circRNAs during periodontitis pathogenesis.
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MicroARNs , Periodontitis , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes/genética , Humanos , MicroARNs/genética , Periodontitis/genética , ARN Circular/genética , ARN Mensajero/genéticaRESUMEN
BACKGROUND: Although Vanins are closely related to neutrophil regulation and response to oxidative stress, and play essential roles in inflammatory diseases with clinical significance, their contribution to periodontitis remains to be determined. This research was designed to assess the expression of Vanins in human gingiva, and to define the relationship between Vanins and periodontitis. METHODS: Forty-eight patients with periodontitis and forty-two periodontal healthy individuals were enrolled for gingival tissue sample collection. Expression levels of VNN1, VNN2 and VNN3 were evaluated by RT-qPCR and validated in datasets GSE10334 and GSE16134. Western blot and immunohistochemistry identified specific proteins within gingiva. The histopathological changes in gingival sections were investigated using HE staining. Correlations between Vanins and clinical parameters, PD and CAL; between Vanins and inflammation, IL1B; and between Vanins and MPO in periodontitis were investigated by Spearman's correlation analysis respectively. Associations between VNN2 and indicators of neutrophil adherence and migration were further validated in two datasets. RESULTS: Vanins were at higher concentrations in diseased gingival tissues in both RT-qPCR and dataset analysis (p < 0.01). Assessment using western blot and immunohistochemistry presented significant upregulations of VNN1 and VNN2 in periodontitis (p < 0.05). The higher expression levels of Vanins, the larger the observed periodontal parameters PD and CAL (p < 0.05), and IL1B (p < 0.001). Moreover, positive correlations existed between VNN2 and MPO, and between VNN2 and neutrophil-related indicators. CONCLUSION: Our study demonstrated upregulation of Vanins in periodontitis and the potential contribution of VNN2 to periodontitis through neutrophils-related pathological processes.
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Periodontitis , Humanos , Periodontitis/metabolismo , Encía/metabolismo , Neutrófilos/metabolismo , Inflamación/patología , ProteínasRESUMEN
OBJECTIVES: This study aimed to clarify the expression profile and significance of lipoxygenases in periodontitis. MATERIALS AND METHODS: The mRNA levels of lipoxygenases in gingival tissues from 14 patients with periodontitis and 14 healthy individuals were determined by real-time PCR, and validated in datasets, GSE16134 and GSE10334, and by Western blotting. Correlation of differentially expressed lipoxygenases with clinical parameters and expression of tumor necrosis factor-α (TNF-α), interleukin-1ß, matrix metalloproteinase (MMP)-8, MMP-9, and receptor activator of nuclear factor-κB ligand (RANKL) was investigated in patients with periodontitis by Spearman's correlation analysis. RESULTS: The expression of ALOX5 (2.1-fold, p < .05), ALOX12B (2.9-fold, p < .001), and ALOX15B (9.4-fold, p < .001) was upregulated in gingival tissues from patients with periodontitis, which was validated by dataset analysis and Western blotting. Positive correlations were observed between ALOX5 and probing depth, and ALOX15B and probing depth and clinical attachment loss. Furthermore, ALOX5 expression was positively correlated with TNF-α, MMP-8, MMP-9, and RANKL expression, and ALOX15B was positively correlated with MMP-8 and RANKL. CONCLUSIONS: Our findings indicated the upregulation of ALOX5 and ALOX15B in periodontitis and suggested that ALOX5 and ALOX15B may be involved in periodontitis pathogenesis, including inflammation, connective tissue destruction, and abnormal bone metabolism.
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Lipooxigenasas , Periodontitis , Encía , Humanos , Inflamación , Periodontitis/genética , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
OBJECTIVE: To summarise the lessons learned from implementing a dental undergraduate research programme over the past eleven years and identify key elements to guarantee the success of dental undergraduate research in the future. MATERIAL AND METHODS: An overview of 80 research projects from 2007 to 2017 was provided, consisting of 239 participating undergraduates and 47 faculty advisors. Students' academic performance was compared between participating and non-participating undergraduates. An anonymous questionnaire was designed and distributed to participants, with VAS satisfaction assessment, Likert-scale items and open-ended questions. Questions focused on overall satisfaction, motivation, benefits to student career development and essential elements for the dental undergraduate research programme in the future. RESULTS: The undergraduate participants had significantly better scores of GPAs (3.41 vs 3.21; P < 0.0001), obtained more awards on the honour rolls (0.53 vs 0.30; P = 0.0171) and published more peer-reviewed articles (1.62 vs 1.31; P = 0.0253) than non-participants. Seventy-two undergraduates (75.79%) and thirty-eight advisors (80.85%) responded to the questionnaire. The overall satisfaction was scored as 78.18/100 and 72.36/100 amongst advisors and students, respectively. Interest was considered the best motivation for participation by students (3.81/5.00) and advisors (4.00/5.00). The research programme was beneficial to students' overall career development. Essential roles played by the dental school, faculty and undergraduates were suggested to improve the research environment. CONCLUSION: The dental undergraduate research programme has positive effects on students' academic performance. The support of the dental school, the engagement of qualified faculty, the interest and autonomy of students and camaraderie amongst these three key elements are essential for the research programme in the future.
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Facultades de Odontología , Estudiantes de Odontología , China , Educación en Odontología , Humanos , MotivaciónRESUMEN
BACKGROUND: The 2019 novel coronavirus disease (COVID-19) has had a massive impact on public health, resulting in sudden dietary and behavioral habit changes. Frontline epidemic prevention workers play a pivotal role against COVID-19. They must face high-risk infection conditions, insufficient anti-epidemic material supplies, mental pressure, and so on. COVID-19 seriously affects their dietary and behavioral habits, and poor habits make them more susceptible to COVID-19. However, their baseline dietary and behavioral habits before COVID-19 and their willingness to change these habits after the outbreak of COVID-19 remain unclear for these workers in China. This study aimed to explore the baseline dietary and behavioral habits of frontline workers and their willingness to change these habits after the outbreak of the epidemic; in addition, susceptible subgroups were identified by stratified analyses as targets of protective measures to keep them from being infected with COVID-19. METHODS: A cross-sectional study was conducted through an online questionnaire using a sample of 22,459 valid individuals living in China, including 9402 frontline epidemic prevention workers. RESULTS: Before COVID-19, 23.9% of the frontline epidemic prevention workers reported a high-salt diet, 46.9% of them reported a high frequency of fried foods intake, and 50.9% of them smoked cigarettes. After the outbreak of COVID-19, 34.6% of them expressed a willingness to reduce salt intake, and 43.7% of them wanted to reduce the frequency of pickled vegetables intake. A total of 37.9% of them expressed a willingness to decrease or quit smoking, and 44.5% of them wanted to increase sleep duration. Significant differences in the baseline dietary and behavioral habits and the willingness to change their habits were observed between frontline epidemic prevention workers and other participants. Among the frontline epidemic prevention workers with poor dietary and behavioral habits before COVID-19, frontline epidemic prevention experience was a promoting factor for adopting worse dietary and behavioral habits, including those in the high-salt intake subgroup (OR, 2.824; 95% CI, 2.341-3.405) and the 11-20 cigarettes/day subgroup (OR, 2.067; 95% CI, 1.359-3.143). CONCLUSIONS: The dietary and behavioral habits of frontline epidemic prevention workers were worse than that those of other participants before COVID-19. They had a greater willingness to adopt healthy dietary and behavioral habits after experiencing the outbreak of COVID-19. However, frontline epidemic prevention workers with poor dietary and behavioral habits before COVID-19 continued in engage in these poor habits. Dietary and behavioral intervention policies should be drafted to protect their health, especially frontline epidemic prevention workers with poor habits at baseline.
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COVID-19/psicología , Dieta/normas , Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud/psicología , Conducta de Reducción del Riesgo , Adulto , COVID-19/prevención & control , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
Goods and services provided by businesses can either promote health or represent an additional risk factor. We assessed the association between business pattern indicators and the prevalence of adult obesity, diabetes, physical inactivity, fair or poor health and frequent physical and mental distress. Data on business types were obtained from the 2013 U.S. Census Bureau County Business Patterns. County health data were obtained from the Centers for Disease Control and Prevention Diabetes Interactive Atlas, Behavior Risk Factor Surveillance System and Fatality Analysis Reporting System. We explored the relationship at county level using the global (Ordinary Least Square regression) and local (Geographically Weighted Regression (GWR)) models in 3108 U.S. counties. Density of full service restaurants and fitness centers was associated with a significant decrease in adult obesity, diabetes, fair or poor health, physical inactivity, physical and mental distress. Conversely, density of payday loan centers was associated with an increase in these adverse health outcomes. However, our GWR models revealed substantial geographical variations in these relationships across the U.S. counties. Better understanding of the association between area-level structures and important health outcomes at the local level is important for developing targeted context-specific policy interventions. Full service restaurants and fitness centers may provide places for people to access higher quality food, socialize and exercise. Conversely, payday loans provide an expensive form of short-term credit and this debt may degrade an individual or family's ability to achieve or maintain health. Our study emphasizes the influence of local built environment characteristics on important health outcomes.
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Enfermedad Crónica/epidemiología , Geografía , Conductas Relacionadas con la Salud , Calidad de Vida , Adulto , Sistema de Vigilancia de Factor de Riesgo Conductual , Comercio/estadística & datos numéricos , Diabetes Mellitus/epidemiología , Ejercicio Físico , Femenino , Humanos , Masculino , Obesidad/epidemiología , Prevalencia , Restaurantes/estadística & datos numéricos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
R2R3-MYB transcription factors play important roles in the regulation of plant flavonoid metabolites. In the current study, NtMYB3, a novel R2R3-MYB transcriptional factor isolated from Chinese narcissus (Narcissus tazetta L. var. chinensis), was functionally characterized. Phylogenetic analysis indicated that NtMYB3 belongs to the AtMYB4-like clade, which includes repressor MYBs involved in the regulation of flavonoid biosynthesis. Transient assays showed that NtMYB3 significantly reduced red pigmentation induced by the potato anthocyanin activator StMYB-AN1 in agro-infiltrated leaves of tobacco. Over-expression of NtMYB3 decreased the red color of transgenic tobacco flowers, with qRT-PCR analysis showing that NtMYB3 repressed the expression levels of genes involved in anthocyanin and flavonol biosynthesis. However, the proanthocyanin content in flowers of transgenic tobacco increased as compared to wild type. NtMYB3 showed expression in all examined narcissus tissues; the expression level in basal plates of the bulb was highest. A 968 bp promoter fragment of narcissus FLS (NtFLS) was cloned, and transient expression and dual luciferase assays showed NtMYB3 repressed the promoter activity. These results reveal that NtMYB3 is involved in the regulation of flavonoid biosynthesis in narcissus by repressing the biosynthesis of flavonols, and this leads to proanthocyanin accumulation in the basal plate of narcissus.
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Flavonoides/biosíntesis , Regulación de la Expresión Génica de las Plantas , Narcissus/genética , Proteínas de Plantas/genética , Factores de Transcripción/genética , Antocianinas/biosíntesis , Flores/genética , Flores/metabolismo , Narcissus/metabolismo , Filogenia , Pigmentación/genética , Proteínas de Plantas/clasificación , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Nicotiana/genética , Nicotiana/metabolismo , Factores de Transcripción/clasificación , Factores de Transcripción/metabolismoRESUMEN
Aim: To explore the association between VPA and weight status in adolescents. Methods: The 2017/2018 Health Behavior in School-aged Children survey (HBSC) targeted children and adolescents aged 11, 13 and 15. A systematic multistage stratified cluster randomized sampling method was used in each participating country. The 2017/2018 survey enrolled over 240,951 adolescents across 45 countries and regions. Frequency of VPA, weight status and confounding factors were collected using a self-reported questionnaire. Results: Compared to daily VPA, less frequent VPA was linked to higher odds of obesity. For example, those who participating in VPA for 4-6 times a week (OR = 1.10, 95% CI = 1.06-1.13), 2-3 times a week (OR = 1.21, 95% CI = 1.17-1.25), or once a week (OR = 1.21, 95% CI = 1.16-1.25) all have higher odds of abnormal weight status. For boys, the frequency of 4-6 times a week (OR = 1.09, 95% CI = 1.04-1.13), 2-3 times a week (OR = 1.22, 95% CI = 1.17-1.27), or once a week (OR = 1.25, 95% CI = 1.19-1.32) were associated with higher odds of abnormal weight status. For girls, those who participating in VPA 4-6 times a week (OR = 1.11, 95% CI = 1.06-1.16), 2-3 times a week (OR = 1.20, 95% CI = 1.14-1.25), or once a week (OR = 1.17, 95% CI = 1.11-1.23) all have higher odds of abnormal weight status (i.e., overweight or obesity). Conclusion: This population-based study suggests that infrequent VPA participation is associated with unhealthy weight status in adolescents compared to their physically active counterparts. Additionally, this association remains consistent in both boys and girls.
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Peso Corporal , Ejercicio Físico , Humanos , Masculino , Femenino , Estudios Transversales , Adolescente , Niño , Encuestas y Cuestionarios , Obesidad Infantil/epidemiología , Autoinforme , Conductas Relacionadas con la SaludRESUMEN
BACKGROUND: Lung cancer remains the foremost reason of cancer-related mortality, with invasion and metastasis profoundly influencing patient prognosis. N-acetyltransferase 10 (NAT10) catalyzes the exclusive N (4)-acetylcytidine (ac4C) modification in eukaryotic RNA. NAT10 dysregulation is linked to various diseases, yet its role in non-small cell lung cancer (NSCLC) invasion and metastasis remains unclear. Our study delves into the clinical significance and functional aspects of NAT10 in NSCLC. METHODS: We investigated NAT10's clinical relevance using The Cancer Genome Atlas (TCGA) and a group of 98 NSCLC patients. Employing WB, qRT-PCR, and IHC analyses, we assessed NAT10 expression in NSCLC tissues, bronchial epithelial cells (BECs), NSCLC cell lines, and mouse xenografts. Further, knockdown and overexpression techniques (siRNA, shRNA, and plasmid) were employed to evaluate NAT10's effects. A series of assays were carried out, including CCK-8, colony formation, wound healing, and transwell assays, to elucidate NAT10's role in proliferation, invasion, and metastasis. Additionally, we utilized lung cancer patient-derived 3D organoids, mouse xenograft models, and Remodelin (NAT10 inhibitor) to corroborate these findings. RESULTS: Our investigations revealed high NAT10 expression in NSCLC tissues, cell lines and mouse xenograft models. High NAT10 level correlated with advanced T stage, lymph node metastasis and poor overall survive. NAT10 knockdown curtailed proliferation, invasion, and migration, whereas NAT10 overexpression yielded contrary effects. Furthermore, diminished NAT10 levels correlated with increased E-cadherin level whereas decreased N-cadherin and vimentin expressions, while heightened NAT10 expression displayed contrasting results. Notably, Remodelin efficiently attenuated NSCLC proliferation, invasion, and migration by inhibiting NAT10 through the epithelial-mesenchymal transition (EMT) pathway. CONCLUSIONS: Our data underscore NAT10 as a potential therapeutic target for NSCLC, presenting avenues for targeted intervention against lung cancer through NAT10 inhibition.
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Carcinoma de Pulmón de Células no Pequeñas , Proliferación Celular , Transición Epitelial-Mesenquimal , Neoplasias Pulmonares , Acetiltransferasa E N-Terminal , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Animales , Ratones , Acetiltransferasa E N-Terminal/metabolismo , Acetiltransferasa E N-Terminal/genética , Masculino , Femenino , Progresión de la Enfermedad , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Desnudos , Persona de Mediana Edad , Acetiltransferasas N-TerminalRESUMEN
INTRODUCTION: Excessive osteoclastogenesis is a key driver of inflammatory bone loss. Suppressing osteoclastogenesis has always been considered essential for the treatment of inflammatory bone loss. N-acetyltransferase 10 (NAT10) is the sole enzyme responsible for N4-acetylcytidine (ac4C) modification of mRNA, and is involved in cell development. However, its role in osteoclastogenesis and inflammatory bone loss remained elusive. OBJECTIVES: We aimed to clarify the regulatory mechanism of NAT10 and ac4C modification in osteoclastogenesis and inflammatory bone loss. METHODS: NAT10 expression and ac4C modification during osteoclastogenesis were determined by quantitative real-time PCR (qPCR), western blotting, dot blot and immunofluorescent staining, and the effect of NAT10 inhibition on osteoclast differentiation in vitro was measured by the tartrate-resistant acid phosphatase staining, podosome belts staining assay and bone resorption pit assay. Then, acRIP-qPCR and NAT10RIP-qPCR, ac4C site prediction, mRNA decay assay and luciferase reporter assay were performed to further study the underlying mechanisms. At last, mice models of inflammatory bone loss were applied to verify the therapeutic effect of NAT10 inhibition in vivo. RESULTS: NAT10 expression was upregulated during osteoclast differentiation and highly expressed in alveolar bone osteoclasts from periodontitis mice. Inhibition of NAT10 notably reduced osteoclast differentiation in vitro, as indicated by great reduction of tartrated resistant acid phosphatse positive multinuclear cells, osteoclast-specific gene expression, F-actin ring formation and bone resorption capacity. Mechanistically, NAT10 catalyzed ac4C modification of Fos (encoding AP-1 component c-Fos) mRNA and maintained its stabilization. Besides, NAT10 promoted MAPK signaling pathway and thereby activated AP-1 (c-Fos/c-Jun) transcription for osteoclastogenesis. Therapeutically, administration of Remodelin, the specific inhibitor of NAT10, remarkably impeded the ligature-induced alveolar bone loss and lipopolysaccharide-induced inflammatory calvarial osteolysis. CONCLUSIONS: Our study demonstrated that NAT10-mediated ac4C modification is an important epigenetic regulation of osteoclast differentiation and proposed a promising therapeutic target for inflammatory bone loss.
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Background: This study utilizes innovative computer vision methods alongside Google Street View images to characterize neighborhood built environments across Utah. Methods: Convolutional Neural Networks were used to create indicators of street greenness, crosswalks, and building type on 1.4 million Google Street View images. The demographic and medical profiles of Utah residents came from the Utah Population Database (UPDB). We implemented hierarchical linear models with individuals nested within zip codes to estimate associations between neighborhood built environment features and individual-level obesity and diabetes, controlling for individual- and zip code-level characteristics (n = 1,899,175 adults living in Utah in 2015). Sibling random effects models were implemented to account for shared family attributes among siblings (n = 972,150) and twins (n = 14,122). Results: Consistent with prior neighborhood research, the variance partition coefficients (VPC) of our unadjusted models nesting individuals within zip codes were relatively small (0.5%-5.3%), except for HbA1c (VPC = 23%), suggesting a small percentage of the outcome variance is at the zip code-level. However, proportional change in variance (PCV) attributable to zip codes after the inclusion of neighborhood built environment variables and covariates ranged between 11% and 67%, suggesting that these characteristics account for a substantial portion of the zip code-level effects. Non-single-family homes (indicator of mixed land use), sidewalks (indicator of walkability), and green streets (indicator of neighborhood aesthetics) were associated with reduced diabetes and obesity. Zip codes in the third tertile for non-single-family homes were associated with a 15% reduction (PR: 0.85; 95% CI: 0.79, 0.91) in obesity and a 20% reduction (PR: 0.80; 95% CI: 0.70, 0.91) in diabetes. This tertile was also associated with a BMI reduction of -0.68 kg/m2 (95% CI: -0.95, -0.40). Conclusion: We observe associations between neighborhood characteristics and chronic diseases, accounting for biological, social, and cultural factors shared among siblings in this large population-based study.
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Passion fruit (Passiflora spp.) is an important fruit tree in the family Passifloraceae. The color of the fruit skin, a significant agricultural trait, is determined by the content of anthocyanin in passion fruit. However, the regulatory mechanisms behind the accumulation of anthocyanin in different passion fruit skin colors remain unclear. In the study, we identified and characterized a R2R3-MYB transcription factor, PeMYB114, which functions as a transcriptional activator in anthocyanin biosynthesis. Yeast one-hybrid system and dual-luciferase analysis showed that PeMYB114 could directly activate the expression of anthocyanin structural genes (PeCHS and PeDFR). Furthermore, a natural variation in the promoter region of PeMYB114 alters its expression. PeMYB114purple accessions with the 224-bp insertion have a higher anthocyanin level than PeMYB114yellow accessions with the 224-bp deletion. The findings enhance our understanding of anthocyanin accumulation in fruits and provide genetic resources for genome design for improving passion fruit quality.
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Antocianinas , Frutas , Regulación de la Expresión Génica de las Plantas , Passiflora , Proteínas de Plantas , Regiones Promotoras Genéticas , Factores de Transcripción , Antocianinas/metabolismo , Antocianinas/genética , Passiflora/genética , Passiflora/metabolismo , Passiflora/química , Frutas/metabolismo , Frutas/genética , Frutas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Mutación INDELRESUMEN
BACKGROUND: Bile acids, as a group of cholesterol metabolites, play important roles in inflammation and bone metabolism. However, the possible link between bile acids and periodontitis is still unclear. This study aimed to clarify the alterations of the bile acid profile and corresponding receptor expression levels in periodontitis patients, and evaluate their association with periodontitis severity. METHODS: The concentrations of 15 bile acids in gingival tissues from 16 periodontitis patients and 16 healthy individuals were tested by metabolomics. Sphingosine-1-phosphate receptor 2 (S1PR2) expression was determined by real-time PCR and immunohistochemistry, which was also validated in two datasets, GSE16134 and GSE10334. The correlation between bile acids, S1PR2, and clinical parameters was analyzed by Spearman's correlation analysis, and receiver-operator characteristic (ROC) curves were examined to access the ability of bile acids and S1PR2 for defining local periodontitis status. RESULTS: In the periodontitis group, concentrations of total bile acids were elevated by increases of all bile acid forms, and five conjugated bile acids were significantly increased. Meanwhile, the expression of their receptor, S1PR2, was also upregulated in the periodontitis group. Positive correlations were further observed between glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), S1PR2, and periodontal clinical parameters. ROC analysis also showed combinations of two bile acids (GCA and TCDCA) with S1PR2 as novel signatures for indicating local periodontitis status. CONCLUSION: Our findings demonstrated the alterations of the bile acid profile and receptor S1PR2 expression in periodontitis patients, and provided evidence of association between bile acids and periodontitis status.
Asunto(s)
Ácidos y Sales Biliares , Periodontitis , Humanos , Receptores de Esfingosina-1-Fosfato , Ácido Tauroquenodesoxicólico , Ácido TaurocólicoRESUMEN
BACKGROUND: To explore the epidemiological characteristics and spatiotemporal distribution of scarlet fever in Liaoning Province, which could provide scientific evidence for the formulation and improvement of prevention and control strategies and measures. METHODS: Data on scarlet fever cases and population were obtained from the China Information System for Disease Control and Prevention in Liaoning Province between 2010 and 2019. We examined the spatial and spatiotemporal clusters of scarlet fever across Liaoning Province using the Moran's I, local indicators of spatial association, local Gi* hotspot statistics, and Kulldorff's retrospective space-time scan statistical analysis. RESULTS: Between 1st January 2010 and 31st December 2019, 46,652 cases of scarlet fever were reported in Liaoning Province, with an annual average incidence of 10.67 per 100,000. The incidence of scarlet fever had obvious seasonality with high incidence in early summer June and early winter December. The male-to-female ratio was 1.53:1. The highest incidence of cases occurred in 3-9 year old children. The most likely spatiotemporal cluster and the secondary clusters were detected in urban regions of Shenyang and Dalian, Liaoning Province. CONCLUSIONS: The incidence of scarlet fever has obvious spatiotemporal clustering, with the high-risk areas mainly concentrated in urban area of Shenyang and Dalian, Liaoning Province. Control strategies need to focus on high-risk season, high-risk areas and high-risk populations in order to reduce the incidence of scarlet fever.
Asunto(s)
Escarlatina , Niño , Humanos , Masculino , Femenino , Preescolar , Escarlatina/epidemiología , Estudios Retrospectivos , China/epidemiología , Estaciones del Año , Análisis por Conglomerados , Incidencia , Análisis Espacio-TemporalRESUMEN
We investigated the content of liberal and conservative news media Facebook posts on race and ethnic health disparities. A total of 3,327,360 liberal and conservative news Facebook posts from the United States (US) from January 2015 to May 2022 were collected from the Crowd Tangle platform and filtered for race and health-related keywords. Qualitative content analysis was conducted on a random sample of 1750 liberal and 1750 conservative posts. Posts were analyzed for a continuum of hate speech using a newly developed method combining faceted Rasch item response theory with deep learning. Across posts referencing Asian, Black, Latinx, Middle Eastern, and immigrants/refugees, liberal news posts had lower hate scores compared to conservative posts. Liberal news posts were more likely to acknowledge and detail the existence of racial/ethnic health disparities, while conservative news posts were more likely to highlight the negative consequences of protests, immigration, and the disenfranchisement of Whites. Facebook posts from liberal and conservative news focus on different themes with fewer discussions of racial inequities in conservative news. Investigating the discourse on race and health in social media news posts may inform our understanding of the public's exposure to and knowledge of racial health disparities, and policy-level support for ameliorating these disparities.