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Infections induced by Gram-positive bacteria pose a great threat to public health. Antibiotic therapy, as the first chosen strategy against Gram-positive bacteria, is inevitably associated with antibiotic resistance selection. Novel therapeutic strategies for the discrimination and inactivation of Gram-positive bacteria are thus needed. Here, a specific type of aggregation-induced emission luminogen (AIEgen) with near-infrared fluorescence emission as a novel antibiotic-free therapeutic strategy against Gram-positive bacteria is proposed. With the combination of a positively charged group into a highly twisted architecture, self-assembled AIEgens (AIE nanoparticles (NPs)) at a relatively low concentration (5 µm) exhibited specific binding and photothermal effect against living Gram-positive bacteria both in vitro and in vivo. Moreover, toxicity assays demonstrated excellent biocompatibility of AIE NPs at this concentration. All these properties make the AIE NPs as a novel generation of theranostic platform for combating Gram-positive bacteria and highlight their promising potential for in vivo tracing of such bacteria.
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Bacterias Grampositivas , Nanopartículas , Nanomedicina Teranóstica , Nanopartículas/química , Bacterias Grampositivas/efectos de los fármacos , Nanomedicina Teranóstica/métodos , Animales , Rayos Infrarrojos , Antibacterianos/farmacología , Antibacterianos/química , Humanos , RatonesRESUMEN
BACKGROUND: Recent research suggests that periodontitis can increase the risk of chronic obstructive pulmonary disease (COPD). In this study, we performed two-sample Mendelian randomization (MR) and investigated the causal effect of periodontitis (PD) on the genetic prediction of COPD. The study aimed to estimate how exposures affected outcomes. METHODS: Published data from the Gene-Lifestyle Interaction in the Dental Endpoints (GLIDE) Consortium's genome-wide association studies (GWAS) for periodontitis (17,353 cases and 28,210 controls) and COPD (16,488 cases and 169,688 controls) from European ancestry were utilized. This study employed a two-sample MR analysis approach and applied several complementary methods, including weighted median, inverse variance weighted (IVW), and MR-Egger regression. Multivariable Mendelian randomization (MVMR) analysis was further conducted to mitigate the influence of smoking on COPD. RESULTS: We chose five single-nucleotide polymorphisms (SNPs) as instrumental variables for periodontitis. A strong genetically predicted causal link between periodontitis and COPD, that is, periodontitis as an independent risk factor for COPD was detected. PD (OR = 1.102951, 95% CI: 1.005-1.211, p = 0.039) MR-Egger regression and weighted median analysis results were coincident with those of the IVW method. According to the sensitivity analysis, horizontal pleiotropy's effect on causal estimations seemed unlikely. However, reverse MR analysis revealed no significant genetic causal association between COPD and periodontitis. IVW (OR = 1.048 > 1, 95%CI: 0.973-1.128, p = 0.2082) MR Egger (OR = 0.826, 95%CI:0.658-1.037, p = 0.1104) and weighted median (OR = 1.043, 95%CI: 0.941-1.156, p = 0.4239). The results of multivariable Mendelian randomization (MVMR) analysis, after adjusting for the confounding effect of smoking, suggest a potential causal relationship between periodontitis and COPD (P = 0.035). CONCLUSION: In this study, periodontitis was found to be independent of COPD and a significant risk factor, providing new insights into periodontitis-mediated mechanisms underlying COPD development.
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Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Enfermedad Pulmonar Obstructiva Crónica , Fumar , Humanos , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Factores de Riesgo , Fumar/epidemiología , Fumar/efectos adversos , Periodontitis/genética , Periodontitis/epidemiología , Índice de Severidad de la Enfermedad , Predisposición Genética a la Enfermedad , Enfermedades Periodontales/genética , Enfermedades Periodontales/epidemiologíaRESUMEN
Accurate prognostic stratification of oral leukoplakia (OLK) with risk of malignant transformation into oral squamous cell carcinoma is crucial. We developed an objective and powerful pathomics-based model for the prediction of malignant transformation in OLK using hematoxylin and eosin (H&E)-stained images. In total, 759 H&E-stained images from multicenter cohorts were included. A training set (n = 489), validation set (n = 196), and testing set (n = 74) were used for model development. Four deep learning methods were used to train and validate the model constructed using H&E-stained images. Pathomics features generated through deep learning combined with machine learning algorithms were used to develop a pathomics-based model. Immunohistochemical staining of Ki67, p53, and PD-L1 was used to interpret the black box of the model. Pathomics-based models predicted the malignant transformation of OLK (validation set area under curve [AUC], 0.899; testing set AUC, 0.813) and significantly identified high-risk and low-risk populations. The prediction performance of malignant transformation from dysplasia grading (validation set AUC, 0.743) was lower than that of the pathomics-based model. The expressions of Ki67, p53, and PD-L1 were correlated with various pathomics features. The pathomics-based model accurately predicted the malignant transformation of OLK and may be useful for the objective and rapid assessment of the prognosis of patients with OLK.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas/patología , Antígeno B7-H1 , Antígeno Ki-67 , Proteína p53 Supresora de Tumor , Leucoplasia Bucal/patología , Transformación Celular Neoplásica/patologíaRESUMEN
BACKGROUND: The association between periodontal disease (PD) and erectile dysfunction (ED) has been well-documented in observational studies. However, observational studies are vulnerable to reverse causality and confounding factors, making the inference of causal-effect relationships challenging. Contrary to the current belief, Mendelian randomization (MR) can be applied to comprehensively assess the bi-directional causal effects between PD and ED. METHODS: A two-sample MR analysis was performed using pooled statistics from genome-wide association studies involving European populations with PD (12,289 patients with PD and 22,326 controls) and ED (6,175 patients with clinically diagnosed ED and 217,630 controls). In this MR analysis, three methods--the inverse-variance weighted (IVW) average, weighted median, and MR-Egger regression methods--were used to evaluate the causal relationships between PD and ED. RESULTS: According to the IVW analysis results, genetically predicted PD did not have a causal effect on ED (odds ratio 1.07, 95% confidence interval 0.96-1.20, p = 0.22). Furthermore, there was no clear indication of a significant causal effect of ED on PD in the reverse MR analysis (odds ratio 0.98, 95% confidence interval 0.90-1.08, p = 0.74). The results of the MR-Egger regression and weighted median methods were consistent with those of the IVW method. Based on the sensitivity analysis results, a major bias from genetic pleiotropy was unlikely to distort the causal estimates. CONCLUSION: The present study does not support a causal effect between PD and ED. CLINICAL RELEVANCE: From the perspective of genetics, PD does not appear to be a risk factor for the development of ED.
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Straw returning is a sustainable way that does not destroy soil ecology in agronomic management. Some studies have found that straw returning may aggravate or reduce soilborne diseases in the past few decades. Despite the increasing number of independent studies investigated the effect of straw returning on root rot of crops, the quantitative analysis regarding the relationship between straw returning and crop root rot is still undefined. In this study, keywords co-occurrence matrix was extracted from 2489 published studies (published from 2000 to 2022, the same below) on controlling soilborne diseases of crops. The methods used for soilborne diseases prevention have shifted from chemical to biological and agricultural control since 2010. As root rot is the soilborne disease with the largest weight in keyword co-occurrence according to statistics, we further collected 531 articles focusing on crop root rot. Notably, the 531 studies are mainly distributed in the United States, Canada, China and other countries in Europe and the south and southeast of Asia, and focus on the root rot of soybean, tomato, wheat and other important grain crops or economic crops. Based on the meta-analysis of 534 measurements in 47 previous studies, we explored how 10 management factors (soil pH/texture, type/size of straw, depth/rate/cumulative amount of application, days after application, beneficial/pathogenic microorganism inoculated before application and annual N-fertilizer input) during straw returning affect root rot onset worldwide. The results showed that straw size and microorganisms inoculated before straw returning are the key factors affecting the incidence of root rot. In combination with actual agricultural production, detailed advice applicable to traditional farming system on the optimization management of straw returning was given. This study emphasized the significance of straw pretreatment and farmland management to reduce soilborne diseases during straw returning.
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Agricultura , Suelo , Suelo/química , Agricultura/métodos , Productos Agrícolas , Grano Comestible , China , FertilizantesRESUMEN
BACKGROUND: Common chronic infections induced low-grade inflammation has been correlated with atherosclerosis as supported by strong evidence. The balance between pro-and anti-inflammatory factors was exploited to elucidate the effects of chronic periodontitis on diabetes-associated atherosclerosis. METHODS: Study subjects encompassed 30 SPF male rats randomly divided into four groups: A group (NC), B group (T2DM), C group (CP), D group (DM + CP). After developing the model, blood samples were collected from the angular vein analyze serum APN, hs-CRP, and blood lipid. the carotid artery was isolated for HE staining. RESULT: Compared with group A, the serum APN in group B, C and D decreased gradually with the progression of the disease. Serum hs-CRP in group B, C and D was significantly increased. At T3, T4 and T5 in group B, C and D, APN/hs-CRP significantly decreased. TC, LDL and TG significantly increased in group B, D; HDL significantly decreased in group C. Carotid artery HE staining showed: compared with group A, different degrees of endothelial defect, destruction of elastic fibers in the middle membrane, disorder of smooth muscle arrangement, and partial dissolution ã fragmentation and Calcium salt deposition necrosis occurred in group B, C and D. CONCLUSION: Enhanced systemic inflammation, decreased adiponectin level, and disorganized lipid metabolism with or without type 2 diabetes attributed to local inflammation of periodontitis can result in an imbalance of pro-inflammatory and anti-inflammatory effects. Therefore, it's more meaningful to predict the progression of DAA with anti-inflammatory/pro-inflammatory variation.
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Aterosclerosis , Periodontitis Crónica , Diabetes Mellitus Tipo 2 , Masculino , Ratas , Animales , Proteína C-Reactiva/metabolismo , Inflamación , Periodontitis Crónica/complicacionesRESUMEN
BACKGROUND: Although obstructive sleep apnea (OSA) and periodontitis are associated, whether this association is causative is uncertain. METHODS: We conducted a bidirectional Mendelian randomization (MR) analysis using data from publically accessible genome-wide association studies. The single-nucleotide polymorphisms (SNPs) for OSA were derived from 16,761 cases and 201,194 controls. The pooled data of periodontitis association involved up to 17,353 individuals. Disease-associated single-nucleotide polymorphisms were selected as an instrumental variable at the genome-wide significance level (p < 5.0 × 10- 6). Subsequently, the causal effects were estimated using three different methods: inverse variance weighting (IVW), MR-Egger, and weighted median. Then, these causal estimates were expressed as dominance ratios [odds ratio (OR)]. RESULTS: The MR analysis revealed that genetically determined OSA promotes the development of periodontitis [ IVW OR = 1.117, 95% confidence interval (CI) = 1.001-1.246, p = 0.048). Furthermore, no causal effect of genetically predicted periodontitis on OSA was noted in the reverse MR analysis (IVW OR = 1, 95% CI: 0.95-1.06, p = 0.87). The trend in results from the MR-Egger regression and weighted median (WM) was consistent with that in results from the IVW method. The robustness of the results was confirmed by the sensitivity analysis. CONCLUSIONS: In summary, the results of our MR investigation suggest an association between OSA and periodontitis, proposing that early screening and treatment of OSA is beneficial for the prevention and prognosis of periodontitis.
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Periodontitis , Apnea Obstructiva del Sueño , Humanos , Estudio de Asociación del Genoma Completo , Oportunidad Relativa , Periodontitis/genética , Polimorfismo de Nucleótido Simple/genética , Apnea Obstructiva del Sueño/genética , Análisis de la Aleatorización MendelianaRESUMEN
OBJECTIVE: Emerging evidence shows the clinical consequences of patient with COVID-19 and periodontitis are not promising, and periodontitis is a risk factor. Periodontitis and COVID-19 probably have a relationship. Hence, this study aimed to identify the common molecular mechanism that may help to devise potential therapeutic strategies in the future. MATERIAL AND METHODS: We analyzed two RNA-seq datasets for differential expressed genes, enrichment of biological processes, transcription factors (TFs) and deconvolution-based immune cell types in periodontitis, COVID-19 and healthy controls. Relationships between TFs and mRNA were established by Pearson correlation analysis, and the common TFs-mRNA regulatory network and nine co-upregulated TFs of the two diseases was obtained. The RT-PCR detected the TFs. RESULTS: A total of 1616 and 10201 differentially expressed gene (DEGs) from periodontitis and COVID-19 are found. Moreover, nine shared TFs and common biological processes associated with lymphocyte activation involved in immune response were identified across periodontitis and COVID-19. The cell type enrichment revealed elevated plasma cells among two diseases. The RT-PCR further confirmed the nine TFs up-regulation in periodontitis. CONCLUSION: The pathogenesis of periodontitis and COVID-19 is closely related to the expression of TFs and lymphocyte activation, which can provide potential targets for treatment.
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COVID-19 , Periodontitis , Humanos , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Periodontitis/genética , Biomarcadores , ARN MensajeroRESUMEN
BACKGROUND: Walnuts (Juglans regia L.) are known for their nutrient-rich nuts and are one of the important economic tree species in the world. However, due to global warming and soil salinization, walnuts suffer from various abiotic stresses. TIFY (TIF[F/Y]XG) proteins play an essential role in the growth and development of plants, signal transduction, and stress response in plants. At present, although the TIFY gene family of a number of plants has been identified and studied, how TIFY takes part in stress tolerance remains obscure and many functions of TIFY require further investigation. RESULT: In this study, twenty-one TIFY transcription factors were identified in the walnut genome database, and they were divided into four subfamilies (TIFY, JAZ, ZML, and PPD) by bioinformatics analysis. Chromosome location revealed tandem duplication of some genes. Phylogenetic tree analysis showed JrTIFYs were closely related to the TIFY gene family of Arabidopsis thaliana (A. thaliana). qRT-PCR (quantitative real-time PCR) analysis revealed the TIFY genes have different expression patterns in 'Qingxiang' and 'Xiangling' walnut varieties under drought, heat, and salt stress. JAZ subfamily was more expressed in different abiotic stress than other subfamilies. The expressions of JrTIFY14 under heat and salt stress were significantly higher than those under drought stress. However, the expression of JrTIFYs was not significant in 'Xiangling'. CONCLUSION: This study reveals the TIFY gene family plays an important role in walnuts facing abiotic stresses and provides a theoretical basis for walnut breeding.
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Juglans , Regulación de la Expresión Génica de las Plantas , Juglans/genética , Familia de Multigenes , Nueces/metabolismo , Filogenia , Fitomejoramiento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genéticaRESUMEN
PURPOSE: Toothache, a common disorder afflicting most people, shows distinct features at different clinical stages. This study aimed to depict metabolic changes in brain and investigate the potential mechanism involved in the aberrant affective behaviors during the natural process of toothache. METHODS: We investigated the spatiotemporal patterns of brain function during the natural course of toothache in a rat model of dental pulp injury (DPI) by using positron emission tomography (PET). RESULTS: Glucose metabolism peaked on the 3rd day and gradually decreased in several brain regions after DPI, which was in line with the behavioral and histological results. PET imaging showed that visual pathway was involved in the regulation of toothache. Meanwhile, the process of emotional regulation underlying toothache was mediated by N-methyl-D-aspartic receptor subunit 2B (NR2B) in the caudal anterior cingulate cortex (cACC). CONCLUSION: Our results revealed the spatiotemporal neurofunctional patterns during toothache process and preliminarily elucidated the role of NR2B in cACC in the regulation of toothache-related affective behaviors.
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Pulpa Dental , Odontalgia , Animales , Encéfalo/diagnóstico por imagen , Pulpa Dental/diagnóstico por imagen , Giro del Cíngulo , Humanos , Ratas , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: Periodontal infections are related to the expansion of diabetes cardiovascular problems. However, the pathological process and probable mechanism remain unexplained. This study investigated the impact of periodontitis on streptozotocin (STZ)-induced diabetes rats' carotid artery. METHODS: We randomized 24 Sprague-Dawley (SD) rats into four groups: control, chronic periodontitis (CP), diabetes mellitus (DM), and DM +CP groups. Fasting blood glucose (FBG) and hemoglobin A1c (HBA1c ) were measured to verify the establishment of the DM model. After euthanasia, the maxillary was collected for further studies like hematoxylin-eosin (HE), Masson staining, and micro-computed tomography (micro-CT) analysis. Immunofluorescence (IF) staining was used to detect endothelial-mesenchymal transition (EndMT)-related markers in carotid artery wall. We further used ELISA and quantitative real-time PCR to investigate the effect of high glucose (HG) and Porphyromonas gingivalis lipopolysaccharide (P.g-LPS) on human umbilical vein endothelial cells (HUVECs). RESULTS: Compared with DM and CP groups, bone resorption and pathological changes of the vascular wall were the most serious in the DM+CP group. The vascular wall of the DM+CP group had a higher level of interleukin (IL)-6 and vascular cell adhesion molecule 1 (VCAM-1). The carotid artery vascular wall of the DM+CP group contained more cells that expressed both mesenchymal and endothelial cell markers, along with elevated transcription factor levels. Furthermore, P.g-LPS and HG upregulated the inflammatory cytokines expression and caused phenotypic changes of HUVECs in vitro. CONCLUSION: Periodontitis exacerbates endothelial dysfunctions partly via endothelial-mesenchymal transition in STZ-induced diabetes rats.
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Periodontitis Crónica , Diabetes Mellitus Experimental , Animales , Periodontitis Crónica/metabolismo , Diabetes Mellitus Experimental/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/patología , Interleucina-6/metabolismo , Lipopolisacáridos/metabolismo , Porphyromonas gingivalis , Ratas , Ratas Sprague-Dawley , Estreptozocina/metabolismo , Microtomografía por Rayos XRESUMEN
BACKGROUND: In March 2021, the supervision group of our hospital inspected the daily work of the outpatient department in the branch and found many problems in the process, such as an excessive number of daily check-up forms, nurses' confusion regarding the daily check-up process, and the omission of daily check-up items. Therefore, focusing on these problem, our hospital established a quality improvement team to conduct a status survey and perform this study. This study evaluated the feasibility, availability and sustainability of using a daily goals sheet in the routine work of a stomatological outpatient department and investigated the satisfaction of the nursing staff with the sheet. METHODS: After determining the theme of this study through the status survey, 60 nurses were randomly selected and divided into an experimental group and a control group by a random grouping method. Then, the study was divided into two stages: Applying the PDCA cycle method and following the MECE (Mad Exclusive, Collectively Exhaustive) principle to design, manufacture and apply the daily goals sheet. After the expert group performed Stage one, an analysis of work efficiency and routine omissions and a staff satisfaction survey were carried out. The results of the groups either using the daily goals sheet (n = 30) or not (n = 30) were analysed and compared. RESULTS: The average work time of the daily goals sheet group was 15.20 ± 1.70 min, and that of the nondaily goals sheet group was 25.30 ± 2.70 min (P < 0.001). The omission rate was 0% in the daily goals sheet group and 16.67% in the nondaily goals sheet group. Staff satisfaction with the use of the daily goals sheet was high. CONCLUSION: The daily goals sheet can make routine work more efficient and convenient in a stomatological outpatient department. It is recommended for use in stomatological outpatient departments or hospitals.
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Personal de Enfermería en Hospital , Satisfacción Personal , Objetivos , Hospitales , Humanos , Satisfacción en el Trabajo , Pacientes Ambulatorios , Mejoramiento de la CalidadRESUMEN
Background and Objectives: The role of α-enolase (ENO1) in Helicobacter pylori-related gastric lesions might be a critical factor in the pathogenesis, but remains undefined. Materials and Methods: This study investigated the differential expression of α-enolase in clinical gastric specimens and cultured normal/cancer cells in response to H. pylori (cagA+) infection and cagA transfection using qPCR, Western blots and histochemical methods. Results: A total of 172 gastric specimens were collected from 142 patients, the former comprising chronic superficial gastritis (CSG), precancerous diseases (PCDs, including atrophic gastritis, intestinal metaplasia and dysplasia) and gastric cancer (GC) cases. Among the CSG and PCD cases, the H. pylori-infected group had significantly elevated ENO1 mRNA levels compared with the uninfected group. In the GC cases, differential ENO1 expressions were detected between the cancer tissues and the paracancerous tissues. Notably, significant difference was first detected between the GC cell (AGS) and the normal cell (GES-1) as a response of ENO1 to H. pylori infection and cagA transfection. Conclusions: This report reveals that ENO1 expression is associated with H. pylori infection, cagA transfection, co-culture duration, multiplicity of infection, gastric normal/cancerous cell lines and cellular differentiation. The findings may be crucial bases for further ascertaining H. pylori pathogenic mechanism and formulating novel therapeutic and diagnostic strategies.
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Infecciones por Helicobacter , Helicobacter pylori , Lesiones Precancerosas , Neoplasias Gástricas , Humanos , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/complicaciones , Fosfopiruvato Hidratasa/genética , Fosfopiruvato Hidratasa/metabolismo , Lesiones Precancerosas/genética , Lesiones Precancerosas/complicaciones , Lesiones Precancerosas/metabolismo , Línea Celular , Transfección , ARN Mensajero/metabolismo , Mucosa Gástrica/metabolismoRESUMEN
Vitamin D is known to play a protective role in inflammatory diseases. Although the suppressive effect of vitamin D/vitamin D receptor (VDR) signaling has been shown in the context of oral lichen planus (OLP), the molecular basis of its regulatory function remains poorly understood. Herein, we reported that miR-802 overexpression in OLP could aggravate apoptosis of oral keratinocytes by targeting B-cell lymphoma 2 mRNA. In addition, vitamin D/VDR signaling was able to suppress miR-802 expression in LPS-treated or activated CD4+ T cell-stimulated human oral keratinocytes by blocking NF-κB pathways, thereby inhibiting OLP apoptosis. Consistent with the results in vitro, we showed that miR-802 expression was enhanced in oral keratinocytes from VDR-/- mice, and an inverse correlation between VDR and miR-802 was found in human biopsy specimens of OLP. Collectively, our data suggest that vitamin D/VDR signaling suppresses oral keratinocyte apoptosis by targeting miR-802.-Zhao, B., Xu, N., Li, R., Yu, F., Zhang, F., Yang, F., Ge, X., Li, Y. C., Du, J. Vitamin D/VDR signaling suppresses microRNA-802-induced apoptosis of keratinocytes in oral lichen planus.
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Apoptosis/fisiología , Queratinocitos/citología , Liquen Plano Oral/patología , MicroARNs/fisiología , Receptores de Calcitriol/metabolismo , Transducción de Señal , Vitamina D/metabolismo , Adulto , Animales , Línea Celular , Femenino , Humanos , Liquen Plano Oral/genética , Liquen Plano Oral/metabolismo , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Receptores de Calcitriol/genética , Regulación hacia ArribaRESUMEN
Selenium (Se) is an essential trace element for humans and other animals, yet approximately one billion people worldwide suffer from Se deficiency. Rice is a staple food for over half of the world's population that is a major dietary source of Se. In paddy soils, rice roots mainly take up selenite. Se speciation analysis indicated that most of the selenite absorbed by rice is predominantly transformed into selenomethinone (SeMet) and retained in roots. However, the mechanism by which SeMet is transported in plants remains largely unknown. In this study, SeMet uptake was found to be an energy-dependent symport process involving H+ transport, with neutral amino acids strongly inhibiting SeMet uptake. We further revealed that NRT1.1B, a member of rice peptide transporter (PTR) family which plays an important role in nitrate uptake and transport in rice, displays SeMet transport activity in yeast and Xenopus oocyte. The uptake rate of SeMet in the roots and its accumulation rate in the shoots of nrt1.1b mutant were significantly repressed. Conversely, the overexpression of NRT1.1B in rice significantly promoted SeMet translocation from roots to shoots, resulting in increased Se concentrations in shoots and rice grains. With vascular-specific expression of NRT1.1B, the grain Se concentration was 1.83-fold higher than that of wild type. These results strongly demonstrate that NRT1.1B holds great potential for the improvement of Se concentrations in grains by facilitating SeMet translocation, and the findings provide novel insight into breeding of Se-enriched rice varieties.
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Proteínas de Transporte de Anión , Oryza , Proteínas de Plantas , Selenio , Proteínas de Transporte de Anión/genética , Proteínas de Transporte de Anión/metabolismo , Transporte Biológico/genética , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/metabolismo , Semillas/genética , Semillas/metabolismo , Selenio/metabolismo , Suelo/químicaRESUMEN
BACKGROUND: Oral lichen planus (OLP) is known as a chronic inflammatory disease. Our recent studies have suggested that vitamin D/vitamin D receptor (VDR) signaling exerts its protective effects on oral keratinocyte apoptosis by regulating microRNA-802 and p53-upregulated modulator of apoptosis (PUMA), but its roles in oral epithelial inflammatory responses in OLP are still unknown. Herein, we identify lipopolysaccharide (LPS) is able to enhance interferon gamma (IFNγ) and interleukin-1 beta (IL-1ß) productions in human oral keratinocytes (HOKs) dependent on hypoxia-inducible factor-1α (HIF-1α). METHODS: HIF-1α and cytokines levels in HOKs were investigated by real-time PCR and western blotting after LPS challenge. The effects of 1,25(OH)2D3 on LPS-induced HIF-1α and cytokines were tested by real-time PCR, western blotting, siRNA-interference and plasmids transfection techniques. The roles of 1,25(OH)2D3 in regulating HIF-1α levels were investigated using western blotting, siRNA-interference, plasmids transfection and Chromatin Immunoprecipitation (ChIP) assays. Finally, HIF-1α, IFNγ and IL-1ß expressions in oral epithelia derived from mice and individuals were measured by real-time PCR, western blotting and immunohistochemical staining. RESULTS: As a critical regulator, vitamin D suppresses LPS-induced HIF-1α to block IFNγ and IL-1ß productions. Mechanistically, vitamin D inactivates nuclear factor-κB (NF-κB) pathway and up-regulates von Hippel-Lindau (VHL) levels, leading to HIF-1α reduction. Moreover, HIF-1α status of oral epithelia is elevated in VDR-/- mie as well as in VDR-deficient human biopsies, accompanied with increased IFNγ and IL-1ß. CONCLUSION: Collectively, this study uncovers an unrecognized roles of vitamin D/VDR signaling in regulating cytokines in oral keratinocytes and reveals the molecular basis of it.
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Epitelio/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Interferón gamma/metabolismo , Interleucina-1beta/metabolismo , Lipopolisacáridos/farmacología , Receptores de Calcitriol/metabolismo , Transducción de Señal , Vitamina D/metabolismo , Animales , Secuencia de Bases , Calcitriol/farmacología , Línea Celular , Epitelio/efectos de los fármacos , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Liquen Plano Oral/metabolismo , Masculino , Ratones Endogámicos C57BL , Boca/metabolismo , FN-kappa B/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismoRESUMEN
OBJECTIVES: Oral lichen planus (OLP) is a chronic inflammatory condition with an unclear pathological mechanism. IκB kinase α (IKKα)-regulated mammary serine protease inhibitor (MASPIN) has been shown to mediate inflammation, particularly in cancers. Here, we explored the expression of MASPIN in OLP and its role in the inflammatory response. MATERIALS AND METHODS: Immunohistochemistry staining and reverse transcription-polymerase chain reaction assays were used to detect the subcellular localization and expression of MASPIN and IKKα in OLP and healthy control tissues. Levels of the inflammatory factors were compared with enzyme-linked immunosorbent assays. MASPIN and IKKα were overexpressed and silenced, respectively, in an inflammation model of human oral keratinocytes (HOKs) stimulated with lipopolysaccharide (LPS). RESULTS: Mammary serine protease inhibitor expression was down-regulated, whereas IKKα expression was up-regulated in OLP tissues (p < 0.01). The levels of tumour necrosis factor-alpha and interleukin-6 in OLP tissues were increased compared to those of healthy controls (p < 0.01). MASPIN overexpression in LPS-stimulated HOK cells inhibited the levels of IKKα and the secretion of inflammatory cytokines. By contrast, IKKα silencing promoted the expression of MASPIN and inhibited the secretion of inflammatory cytokines. CONCLUSION: Both MASPIN and IKKα are involved in the inflammatory process of OLP, suggesting potential therapeutic targets.
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Citocinas/metabolismo , Liquen Plano Oral/metabolismo , Inhibidores de Serina Proteinasa/metabolismo , Adulto , Anciano , Citocinas/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Queratinocitos , Lipopolisacáridos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Inhibidores de Serina Proteinasa/genética , SerpinasRESUMEN
OBJECTIVE: There are challenges in the treatment of chronic inflammatory diseases of oral mucosa. Both paeoniflorin (PF) and baicalin (BAI) exert anti-inflammatory effects, but the mechanism underlying their combined effects is still unclear. Here, we explored the anti-inflammatory function of the PF-BAI combination in the oral inflammatory response. MATERIALS AND METHODS: The CCK-8 assay was used to determine the proliferative capacity of HOKs with PF and BAI. Enzyme-linked immunosorbent (ELISA), Western blotting, reverse transcription polymerase chain reaction, and confocal immunofluorescence were performed to study the anti-inflammatory effects of PF-BAI in LPS-stimulated human oral keratinocytes (HOKs). Immunohistochemistry and ELISA were performed to detect the levels of NF-κB p65, IKKα and IL-6, TNF-α in OLP and healthy tissues. RESULTS: Compared to PF or BAI alone, the combination of PF-BAI at 5 µg/ml downregulated secretion of inflammatory cytokines more effectively (p < .05). Combined PF-BAI decreased NF-κB p65 and IκBα protein phosphorylation, leading to reduce nuclear translocation of NF-κB p65. Higher expression of TNF-α, IL-6, NF-κB p65, and IKKα were observed in OLP than in HC tissues (p < .01). CONCLUSION: The optimal combination concentration of PF and BAI at 5 µg/ml may have a positive effect on the treatment of oral inflammatory diseases, providing a novel therapeutic approach.
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Antiinflamatorios no Esteroideos/farmacología , Flavonoides/farmacología , Glucósidos/farmacología , Mediadores de Inflamación/metabolismo , Liquen Plano Oral/tratamiento farmacológico , Monoterpenos/farmacología , FN-kappa B/metabolismo , Periodontitis/tratamiento farmacológico , Citocinas , Humanos , Inflamación/inducido químicamente , Inflamación/metabolismo , Lipopolisacáridos , FN-kappa B/antagonistas & inhibidoresRESUMEN
To test the alternative possible locations for the placement of a liver graft and the relevant surgical technique issues, we developed a porcine model of auxiliary partial heterotopic liver transplantation (APHLT) and evaluated the difference between 2 styles of liver transplantation, either subhepatic fossa or splenic fossa APHLT, by comparing survival and biochemical indexes. Thirty-eight miniature pigs were randomly divided into 2 groups. A left hemihepatic graft without the middle hepatic vein (HV) was procured from the living donor. In group A (n = 9), an 8 mm diameter polytetrafluoroethylene (PTFE) graft approximately 2.5 cm long was connected to the left HV while another PTFE graft of the same size was connected to the left portal vein (PV). The liver graft was implanted in the right subhepatic fossa following splenectomy and right nephrectomy. In group B (n = 10), a PTFE graft of the same size was connected to the left HV while the liver graft was implanted in the splenic fossa following splenectomy and left nephrectomy. Survival rate and complications were observed at 2 weeks after transplantation. Data were collected from 5 animals in group A and 6 animals in group B that survived longer than 2 weeks. The liver function and renal function of the recipients returned to normal at 1 week after surgery in both groups. Eighty-eight percent (14/16) of the PTFE grafts remained patent at 2 weeks after surgery, but 44% of the PTFE grafts (7/16) developed mural thrombus. No significant differences in the survival rate and biochemistry were found between the 2 groups. In conclusion, the splenic fossa APHLT can achieve beneficial outcomes similar to the subhepatic fossa APHLT in miniature pigs, although it also has a high morbidity rate due to hepatic artery thrombosis, PV thrombosis, and PTEF graft mural thrombus formation. Liver Transplantation 22 812-821 2016 AASLD.
Asunto(s)
Trasplante de Hígado/métodos , Complicaciones Posoperatorias/etiología , Trombosis/etiología , Trasplante Heterotópico/métodos , Injerto Vascular/métodos , Aloinjertos/patología , Animales , Prótesis Vascular , Estudios de Factibilidad , Femenino , Arteria Hepática/patología , Venas Hepáticas/cirugía , Humanos , Estimación de Kaplan-Meier , Hígado/irrigación sanguínea , Hígado/patología , Hígado/cirugía , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Donadores Vivos , Modelos Animales , Nefrectomía/métodos , Politetrafluoroetileno , Vena Porta/cirugía , Distribución Aleatoria , Esplenectomía/métodos , Porcinos , Porcinos Enanos , Trasplante Heterotópico/efectos adversos , Trasplante Heterotópico/mortalidad , Injerto Vascular/efectos adversos , Injerto Vascular/instrumentación , Injerto Vascular/mortalidadRESUMEN
⢠Selenite is a predominant form of selenium (Se) available to plants, especially in anaerobic soils, but the molecular mechanism of selenite uptake by plants is not well understood. ⢠ltn1, a rice mutant previously shown to have increased phosphate (Pi) uptake, was found to exhibit higher selenite uptake than the wild-type in both concentration- and time-dependent selenite uptake assays. Respiratory inhibitors significantly inhibited selenite uptake in the wildtype and the ltn1 mutant, indicating that selenite uptake was coupled with H(+) and energy-dependent. Selenite uptake was greatly enhanced under Pi-starvation conditions, suggesting that Pi transporters are involved in selenite uptake. ⢠OsPT2, the most abundantly expressed Pi transporter in the roots, is also significantly up-regulated in ltn1 and dramatically induced by Pi starvation. OsPT2-overexpressing and knockdown plants displayed significantly increased and decreased rates of selenite uptake, respectively, suggesting that OsPT2 plays a crucial role in selenite uptake. Se content in rice grains also increased significantly in OsPT2-overexpressing plants. ⢠These data strongly demonstrate that selenite and Pi share similar uptake mechanisms and that OsPT2 is involved in selenite uptake, which provides a potential strategy for breeding Se-enriched rice varieties.