RESUMEN
Plant genomes encode many receptor-like kinases (RLKs) that localize to the cell surface and perceive a wide variety of environmental cues to initiate downstream signaling cascades. Whether these RLKs participate in dehydration stress signaling in plants is largely unknown. DROOPY LEAF1 (DPY1), a leucine-rich repeat (LRR)-RLK, was recently shown to regulate plant architecture by orchestrating early brassinosteroid signaling in foxtail millet (Setaria italica). Here, we show that DPY1 is essential for the acclimation of foxtail millet to drought stress. DPY1 can be phosphorylated and activated in response to osmotic stress and is required for more than half of osmotic stress-induced global phosphorylation events, including the phosphorylation of sucrose nonfermenting kinase 2s (SnRK2s), the central kinases involved in osmotic stress. DPY1 acts upstream of STRESS-ACTIVATED PROTEIN KINASE 6 (SAPK6, a subclass I SnRK2) and is required for full SAPK6 activation, thereby allowing regulation of downstream genes to mount a response against drought stress. These signaling events are largely independent of DPY1-mediated brassinosteroid signaling. The DPY1-SAPK6 module is specific to seed plants and is absent in ancestral nonseed plants. Our findings reveal a dehydration stress-activated RLK that plays an indispensable role in osmotic stress signaling and mediates SnRK2 activation at the cell surface.
Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Setaria (Planta) , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Presión Osmótica/fisiología , Setaria (Planta)/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Resistencia a la Sequía , Brasinoesteroides/metabolismo , Deshidratación , Ácido Abscísico/metabolismo , Plantas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Type 2 diabetes mellitus (T2DM) was reported to be associated with impaired immune response and alterations in microbial composition and function. However, the underlying mechanism remains elusive. To investigate the association among retinoic acid-inducible gene-I-like receptors (RLRs) signaling pathway, intestinal bacterial microbiome, microbial tryptophan metabolites, inflammation, and a longer course of T2DM, 14 patients with T2DM and 7 healthy controls were enrolled. 16S rRNA amplicon sequencing and untargeted metabolomics were utilized to analyze the stool samples. RNA sequencing (RNA-seq) was carried out on the peripheral blood samples. Additionally, C57BL/6J specific pathogen-free (SPF) mice were used. It was found that the longer course of T2DM could lead to a decrease in the abundance of probiotics in the intestinal microbiome. In addition, the production of microbial tryptophan derivative skatole declined as a consequence of the reduced abundance of related intestinal microbes. Furthermore, low abundances of probiotics, such as Bacteroides and Faecalibacterium, could trigger the inflammatory response by activating the RLRs signaling pathway. The increased level of the member of TNF receptor-associated factors (TRAF) family, nuclear factor kappa-B (NF-κB) activator (TANK), in the animal colon activated nuclear factor kappa B subunit 2 (NFκB2), resulting in inflammatory damage. In summary, it was revealed that the low abundances of probiotics could activate the RLR signaling pathway, which could in turn activate its downstream signaling pathway, NF-κB, highlighting a relationship among gut microbes, inflammation, and a longer course of T2DM. KEY POINTS: Hyperglycemia may suppress tryptophanase activity. The low abundance of Bacteroides combined with the decrease of Dopa decarboxylase (DDC) activity may lead to the decrease of the production of tryptophan microbial derivative skatole, and the low abundance of Bacteroides or reduced skatole may further lead to the increase of blood glucose by downregulating the expression of glucagon-like peptide-1 (GLP1). A low abundance of anti-inflammatory bacteria may induce an inflammatory response by triggering the RLR signaling pathway and then activating its downstream NF-κB signaling pathway in prolonged T2DM.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Ratones , Animales , Humanos , Ratones Endogámicos C57BL , FN-kappa B , ARN Ribosómico 16S/genética , Escatol , Triptófano , Inflamación , Bacteroides/genéticaRESUMEN
Cellular senescence severely limits the research and the application of dental pulp stem cells (DPSCs). A previous study conducted by our research group revealed a close implication of ROR2 in DPSC senescence, although the mechanism underlying the regulation of ROR2 in DPSCs remains poorly understood so far. In the present study, it was revealed that the expression of the ROR2-interacting transcription factor MSX2 was increased in aging DPSCs. It was demonstrated that the depletion of MSX2 inhibits the senescence of DPSCs and restores their self-renewal capacity, and the simultaneous overexpression of ROR2 enhanced this effect. Moreover, MSX2 knockdown suppressed the transcription of NOP2/Sun domain family member 2 (NSUN2), which regulates the expression of p21 by binding to and causing the 5-methylcytidine methylation of the 3'- untranslated region of p21 mRNA. Interestingly, ROR2 downregulation elevated the levels of MSX2 protein, and not the MSX2 mRNA expression, by reducing the phosphorylation level of MSX2 and inhibiting the RNF34-mediated MSX2 ubiquitination degradation. The results of the present study demonstrated the vital role of the ROR2/MSX2/NSUN2 axis in the regulation of DPSC senescence, thereby revealing a potential target for antagonizing DPSC aging.
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Senescencia Celular , Pulpa Dental , Senescencia Celular/genética , Pulpa Dental/metabolismo , Regulación hacia Abajo/genética , Regulación de la Expresión Génica , ARN Mensajero/genéticaRESUMEN
Seed storage proteins (SSPs) are of great importance in plant science and agriculture, particularly in cereal crops, due to their nutritional value and their impact on food properties. During seed maturation, massive amounts of SSPs are synthesized and deposited either within protein bodies derived from the endoplasmic reticulum, or into specialized protein storage vacuoles (PSVs). The processing and trafficking of SSPs vary among plant species, tissues, and even developmental stages, as well as being influenced by SSP composition. The different trafficking routes, which affect the amount of SSPs that seeds accumulate and their composition and modifications, rely on a highly dynamic and functionally specialized endomembrane system. Although the general steps in SSP trafficking have been studied in various plants, including cereals, the detailed underlying molecular and regulatory mechanisms are still elusive. In this review, we discuss the main endomembrane routes involved in SSP trafficking to the PSV in Arabidopsis and other eudicots, and compare and contrast the SSP trafficking pathways in major cereal crops, particularly in rice and maize. In addition, we explore the challenges and strategies for analyzing the endomembrane system in cereal crops.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Grano Comestible/metabolismo , Transporte de Proteínas , Proteínas de Almacenamiento de Semillas/metabolismo , Semillas/metabolismo , Vacuolas/metabolismoRESUMEN
Under nutrient and energy-limiting conditions, plants up-regulate sophisticated catabolic pathways such as autophagy to remobilize nutrients and restore energy homeostasis. Autophagic flux is tightly regulated under these circumstances through the AuTophaGy-related1 (ATG1) kinase complex, which relays upstream nutrient and energy signals to the downstream components that drive autophagy. Here, we investigated the role(s) of the Arabidopsis (Arabidopsis thaliana) ATG1 kinase during autophagy through an analysis of a quadruple mutant deficient in all four ATG1 isoforms. These isoforms appear to act redundantly, including the plant-specific, truncated ATG1t variant, and like other well-characterized atg mutants, homozygous atg1abct quadruple mutants display early leaf senescence and hypersensitivity to nitrogen and fixed-carbon starvations. Although ATG1 kinase is essential for up-regulating autophagy under nitrogen deprivation and short-term carbon starvation, it did not stimulate autophagy under prolonged carbon starvation. Instead, an ATG1-independent response arose requiring phosphatidylinositol-3-phosphate kinase (PI3K) and SUCROSE NONFERMENTING1-RELATED PROTEIN KINASE1 (SnRK1), possibly through phosphorylation of the ATG6 subunit within the PI3K complex by the catalytic KIN10 subunit of SnRK1. Together, our data connect ATG1 kinase to autophagy and reveal that plants engage multiple pathways to activate autophagy during nutrient stress, which include the ATG1 route as well as an alternative route requiring SnRK1 and ATG6 signaling.plantcell;31/12/2973/FX1F1fx1.
Asunto(s)
Proteínas de Arabidopsis/genética , Arabidopsis/enzimología , Arabidopsis/genética , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Autofagia/genética , Carbono/deficiencia , Proteínas de la Membrana/genética , Proteínas Mitocondriales/genética , Compuestos de Amonio/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Autofagia/fisiología , Homólogo de la Proteína 1 Relacionada con la Autofagia/genética , Proteínas Relacionadas con la Autofagia/genética , Proteínas Relacionadas con la Autofagia/metabolismo , Beclina-1/química , Beclina-1/genética , Beclina-1/metabolismo , Carbono/metabolismo , Proteínas de la Membrana/metabolismo , Mutación , Nitrógeno/deficiencia , Nitrógeno/metabolismo , Fenotipo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Isoformas de Proteínas , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal/genética , Factores de Transcripción/metabolismo , Vacuolas/genética , Vacuolas/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismoRESUMEN
Smoking-mediated reprogramming of the phenotype and function of airway basal cells (BCs) disrupts airway homeostasis and is an early event in chronic obstructive pulmonary disease (COPD)-associated airway remodeling. Here, we examined the expression and regulation of the transmembrane glycoprotein TROP2 (trophoblast antigen 2), a putative stem cell marker in airway BCs, in lung tissue samples from healthy smokers and healthy nonsmokers and in models in culture to identify therapeutic targets. TROP2 expression was upregulated in the airway epithelia of smokers and positively correlated with the smoking index. In vitro, cigarette smoke extract (CSE) induced TROP2 expression in airway BCs in a time- and dose-dependent manner. The p38 MAPK and NF-κB pathways were also activated by CSE, and their specific antagonists inhibited CSE-induced TROP2 expression. A therapeutic component derived from traditional Chinese medicine, ginsenoside Rb3, inhibited CSE-induced TROP2 expression as well as activation of the p38 MAPK and NF-κB pathways in BCs in monolayer culture. Furthermore, ginsenoside Rb3 prevented the increase in TROP2 expression and antagonized CSE-induced BC hyperplasia and expression of inflammatory factors and epithelial-mesenchymal transition changes in an air-liquid culture model. Thus, CSE-induced TROP2 is a possible biomarker for early changes in the epithelium of smokers, and ginsenoside Rb3 may serve as a therapeutic molecule, preventing the disruption of epithelial homeostasis in COPD.
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Antígenos de Neoplasias/metabolismo , Moléculas de Adhesión Celular/metabolismo , Ginsenósidos/farmacología , Pulmón/patología , FN-kappa B/metabolismo , Transducción de Señal , Fumar/efectos adversos , Regulación hacia Arriba/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Epitelio/metabolismo , Femenino , Humanos , Hiperplasia , Mediadores de Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Fosforilación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Factores de TiempoRESUMEN
ABSTRACT: This study aimed to evaluate the protective effect of quercetin and its in-depth mechanism in TNF-α-stimulated cardiomyocytes. The differential expression of TNF-alpha (TNF-α) and signal transducer and activator of transcription 1 (STAT1) was analyzed based on the GEO database. H9c2 cells were stimulated with TNF-α to simulate myocarditis. Cell counting kit-8 assay and flow cytometry assay were performed to detect the cell viability and apoptosis. ELISA was used to measure the levels of proinflammatory cytokines (IL-6 and IL-17A) and anti-inflammatory cytokine (IL-10). STAT1 expression was downregulated by transfection with si-STAT1, and its expression was detected using quantitative real-time polymerase chain reaction and Western blot. Western blot was also performed to assess the expression of the mitogen-activated protein kinase (MAPK) pathway-related factors. In this article, TNF-α was highly expressed in patients with myocarditis, and TNF-α (20 µg/mL) declined the viability of H9c2 cells. Quercetin pretreatment partially alleviated the decrease of cell viability, the increase of apoptosis, and the release of inflammatory cytokines (IL-10, IL-6, and IL-17A) induced by TNF-α. In addition, TNF-α increased STAT1 expression, but quercetin prevented the TNF-α-increased STAT1 level. Remarkably, knockdown of STAT1 enhanced the protective effect of quercetin on TNF-α-injured H9c2 cells. Moreover, quercetin restrained the TNF-α-induced activation of the MAPK pathway. Also, the inhibitory effect of quercetin on the pathway was aggravated by STAT1 lacking. In summing, quercetin plays a protective role in TNF-α-stimulated H9c2 cell injury, which may be related to the regulation of STAT1 and MAPK pathway.
Asunto(s)
Antiinflamatorios/farmacología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Miocarditis/tratamiento farmacológico , Miocitos Cardíacos/efectos de los fármacos , Quercetina/farmacología , Factor de Transcripción STAT1/metabolismo , Animales , Estudios de Casos y Controles , Línea Celular , Humanos , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Miocarditis/enzimología , Miocarditis/genética , Miocarditis/patología , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/patología , Ratas , Factor de Transcripción STAT1/genética , Transducción de Señal , Factor de Necrosis Tumoral alfa/toxicidadRESUMEN
Despite the wide application of cobalt nanoparticles (CoNPs), its neurotoxicity and the underlying mechanisms are not fully understood. In this study, CoNPs-induced toxic effect was examined in both C57BL/6J mice and microglial BV2 cells. CoNPs-induced brain weight loss and the reduction of Nissl bodies, assuring neural damage. Moreover, both total unphosphorylated Tau and phosphorylated Tau (pTau; T231 and S262) expressions in the hippocampus and cortex were upregulated, unveiling Tau phosphorylation. Besides, the increase in inflammation-related proteins NLRP3 and IL-1ß were found in mice brain. Corroborating that, microglial marker Iba-1 expression was also increased, suggesting microglia-involved inflammation. Among the NADPH oxidase (NOX) family proteins tested, only NOX2 was activated by CoNPs in hippocampus. Therefore, BV2 cells were employed to further investigate the role of NOX2. In BV2 cells, NOX2 expression was upregulated, corresponding to the production of ROS. Moreover, similar induction in Tau phosphorylation and inflammation-related protein expressions were observed in CoNPs-exposed BV2 cells. Treatment of apocynin, a NOX2 inhibitor, reduced ROS generation and reversed Tau phosphorylation and inflammation caused by CoNPs. Thus, CoNPs induced ROS production, Tau phosphorylation and inflammation specially via NOX2 activation.
Asunto(s)
Microglía , Nanopartículas , Animales , Cobalto , Ratones , Ratones Endogámicos C57BL , FosforilaciónRESUMEN
Cobalt nanoparticles (CoNPs) have been widely used in industry given their physical, chemical and magnetic properties; however, CoNPs may cause neurological symptoms and diseases in human, yet their mechanisms of toxicity remain unknown. Here, we used male Wistar rats to investigate differences in the toxic effects associated with CoNPs and CoCl2. Upon exposure to CoCl2, and 96â¯nm or 123â¯nm CoNPs at the same concentration, the Co2+ content in CoCl2 group was significantly higher than that in either the CoNPs groups in brain tissues and blood, but lower in liver. Significant neural damage was observed in both hippocampus and cortex of the temporal lobe. Increase malondialdehyde (MDA) content and CASPASE 9 protein level were associated both with CoCl2 and CoNPs treatments, consistent with lipid perioxidation and apoptosis. Heme oxygenase-1 and (NF-E2) p45-related factor-2 protein levels were elevated in response to 96â¯nm CoNPs exposure. In PC12 cells, NRF2 downregulation led to reduced cell viability and increased apoptotic rate. In conclusion, both CoNPs and CoCl2 cause adverse neural effects, with nanoparticles showing greater neurotoxic potency. In addition, NRF2 protects neural cells from damage induced by CoCl2 and CoNPs by activating downstream antioxidant responses.
Asunto(s)
Encéfalo/efectos de los fármacos , Cobalto/toxicidad , Nanopartículas del Metal/toxicidad , Neuronas/efectos de los fármacos , Síndromes de Neurotoxicidad/etiología , Animales , Apoptosis/efectos de los fármacos , Biomarcadores/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Caspasa 9/metabolismo , Cobalto/sangre , Hemo Oxigenasa (Desciclizante)/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Subunidad p45 del Factor de Transcripción NF-E2/metabolismo , Neuronas/metabolismo , Neuronas/patología , Síndromes de Neurotoxicidad/sangre , Síndromes de Neurotoxicidad/patología , Células PC12 , Ratas , Ratas Wistar , Medición de Riesgo , Distribución TisularRESUMEN
BACKGROUND: Epstein-Barr virus (EBV) infection is causatively associated with a variety of human cancers, including gastric cancer (GC), which has one of the highest mortality rates of all human cancers. Long non-coding RNAs (lncRNAs) show important regulatory roles in human GC. SNHG8 is a recently identified lncRNA that was reported to show abnormal expression pattern in GC. However, little is known of its biological function in EBV-associated GC. METHODS: We used cell viability, colony formation and cell cycle assays to investigate the roles of lncRNA SNHG8 in the cell growth of EBV-associated GC. RESULTS: The transcript levels of SNHG8 in the cultured EBV-associated GC cells were significantly higher in the cultured EBV-associated GC cells compared with the levels in normal human gastric mucosal cells and EBV-negative GC cells. Knockdown of SNHG8 with specific shRNAs inhibited cell proliferation and colony formation and arrested the cell cycle in the G0/G1 phase in vitro. We also found that knockdown of SNHG8 suppressed tumor growth in vivo. CONCLUSIONS: These data indicate the pro-oncogenic potential of SNHG8 in EBV-associated GC, meaning it is a latent therapeutic target for the treatment of this type of cancer.
Asunto(s)
Infecciones por Virus de Epstein-Barr/metabolismo , ARN Largo no Codificante/metabolismo , Neoplasias Gástricas/virología , Animales , Apoptosis , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/genética , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , ARN Largo no Codificante/genética , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The objective of this study was to evaluate the toxicity of flavor enhancers to the oriental fruit fly Bactrocera dorsalis (Hendel). The flavor enhancers glycine, disodium guanylate, succinic acid disodium salt, monosodium glutamate (MSG), disodium inosinate, and L-alanine significantly increased the mortality of B. dorsalis flies. The mortality of flies that fed on glycine, disodium guanylate, succinic acid disodium salt, and MSG was greater than 90%. Additionally, fruit fly mortality increased with increases in both time and concentration. Glycine not only reduced the climbing ability of B. dorsalis but also affected the duration and frequency of its behavioral patterns (flight, walking, grooming and inactivity). Compared with adult flies in the control group, adult B. dorsalis flies that fed on glycine exhibited a significantly increased duration and frequency of inactivity and a decreased duration and frequency of both flight and walking. However, the effect of glycine on grooming activity was not significant. These findings demonstrate the toxic effects of flavor enhancers on B. dorsalis. Glycine also affected the behavior of adult flies at a low dose. Therefore, glycine has potentially toxic to insects and also likely to have a negative impact at sublethal concentrations.
Asunto(s)
Contaminantes Ambientales/toxicidad , Aromatizantes/toxicidad , Glicina/toxicidad , Tephritidae/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Femenino , Locomoción/efectos de los fármacos , MasculinoRESUMEN
BACKGROUND: Geographic isolation is an important factor that limit species dispersal and thereby affects genetic diversity. Because islands are often small and surrounded by a natural water barrier to dispersal, they generally form discrete isolated habitats. Therefore, islands may play a key role in the distribution of the genetic diversity of insects, including flies. RESULTS: To characterize the genetic structure of island populations of Bactrocera dorsalis, we analyzed a dataset containing both microsatellite and mtDNA loci of B. dorsalis samples collected from six offshore islands in Southern China. The microsatellite data revealed a high level of genetic diversity among these six island populations based on observed heterozygosity (Ho), expected heterozygosity (HE), Nei's standard genetic distance (D), genetic identity (I) and the percentage of polymorphic loci (PIC). These island populations had low F ST values (F ST = 0.04161), and only 4.16 % of the total genetic variation in the species was found on these islands, as determined by an analysis of molecular variance. Based on the mtDNA COI data, high nucleotide diversity (0.9655) and haplotype diversity (0.00680) were observed in all six island populations. F-statistics showed that the six island populations exhibited low or medium levels of genetic differentiation among some island populations. To investigate the population differentiation between the sampled locations, a factorial correspondence analysis and both the unweighted pair-group method with arithmetic mean and Bayesian clustering methods were used to analyze the microsatellite data. The results showed that Hebao Island, Weizhou Island and Dong'ao Island were grouped together in one clade. Another clade consisted of Shangchuan Island and Naozhou Island, and a final, separate clade contained only the Wailingding Island population. Phylogenetic analysis of the mtDNA COI sequences revealed that the populations on each of these six islands were closely related to different populations on mainland China. CONCLUSIONS: Our study suggests that these island populations have high genetic diversity, experience frequent gene flow and exhibit low or medium levels of genetic differentiation among some island populations. Therefore, the geographic isolation of the six islands does not appear to be a major dispersal barrier to B. dorsalis. Such knowledge is helpful for a better understanding of evolutionary processes of the species of island populations.
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Variación Genética , Tephritidae/genética , Animales , China , ADN Mitocondrial/genética , Ecosistema , Evolución Molecular , Femenino , Flujo Génico , Haplotipos , Islas , Masculino , Filogenia , Tephritidae/clasificación , Tephritidae/crecimiento & desarrolloRESUMEN
The biological model of extraversion and neuroticism identified by Eysenck has stimulated increasing interest in uncovering neurobiological substrate of the two fundamental dimensions. Here we aim to explore brain disturbances underlying extraversion and neuroticism in 87 healthy individuals using fractional amplitude of low-frequency fluctuations (LFF) on resting-state functional magnetic resonance imaging. Two different frequency bands, Slow-5 (0.01-0.027 Hz) exhibiting higher power and involving larger brain regions, and Slow-4 (0.027-0.073 Hz) exhibiting less power and emerging locally, were analyzed. Our results showed a positive correlation between LFF amplitude at Slow-5 and extraversion in medial prefrontal cortex and precuneus, important portions of the default mode network, thus suggesting a link between default network activity and personality traits. LFF amplitude at Slow-5 was correlated positively with neuroticism in right posterior portion of the frontal lobe, further validating neuroticism with frontal lateralization. In addition, LFF amplitude at Slow-4 was negatively associated with extraversion and neuroticism in left hippocampus (HIP) and bilateral superior temporal cortex (STC) respectively, supporting the hypothesized (inverse) relationship between extraversion and resting arousal, also implying neural circuit underlying emotional process influencing on personality. Overall, these findings suggest the important relationships, between personality and LFF amplitude dynamic, depend on specific frequency bands.
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Trastornos de Ansiedad/fisiopatología , Mapeo Encefálico , Encéfalo/fisiología , Extraversión Psicológica , Adolescente , Adulto , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Neuroticismo , Personalidad/fisiología , Descanso/fisiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Acute and chronic respiratory diseases are associated with abnormal coagulation regulation and fibrolysis. However, the detailed mechanism by which coagulation regulation and fibrolysis affect the occurrence and development of lung diseases remain to be elucidated. Protease activated receptor-1 (PAR-1), a major high-affinity thrombin receptor, and nuclear factor kappa B (NF-κB), a transcription factor, are involved in cell survival, differentiation, and proliferation. We have investigated the potential mechanism of thrombin-induced fibroblast proliferation and roles of PAR-1 and NF-κB signalling in this process. The effect of thrombin on proliferation of human pulmonary fibroblasts (HPF) was assessed by 5-bromo-2-deoxyuridine (BrdU) incorporation assay. The expression of PAR1 and NF-κB subunit p65 protein was detected by Western blot. Nuclear translocation of p65 was examined by laser scanning confocal microscopy. We show that thrombin significantly increased proliferation of HPF as determined by induction of BrdU-positive incorporation ratio. Induced PAR1 protein expression was also seen in HPF cells treated with thrombin. However, thrombin had no significant effect on expression and translocation of NF-κB p65 in HPF cells. The results indicate that, by increasing protein expression and interacting with PAR1, thrombin promotes HPF proliferation. NF-κB signalling appears to play no role in this process.
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Pulmón/citología , Receptor PAR-1/metabolismo , Trombina/metabolismo , Factor de Transcripción ReIA/metabolismo , Transporte Activo de Núcleo Celular , Antitrombinas/farmacología , Coagulación Sanguínea , Línea Celular , Proliferación Celular , Fibrinólisis , Fibroblastos/citología , Hirudinas/farmacología , Humanos , Enfermedades Pulmonares , Receptor PAR-1/biosíntesis , Transducción de Señal , Trombina/antagonistas & inhibidores , Factor de Transcripción ReIA/biosíntesisRESUMEN
OBJECTIVE: To evaluate the effects of a commercial bleaching agent containing 35% (mass fraction) hydrogen peroxide on the growth of Streptococcus mutans biofilm on enamel disc surface. METHODS: A total of 20 enamel disks were made from human extracted teeth and the enamel surfaces were kept intact. The discs were autocalved and randomly divided into two groups: bleaching group and control group. Each group contained 10 discs. For bleaching group, the enamel discs were whitened by commercial 35% hydrogen peroxide according to the instruction (Beyond(TM) Professional Dental Whitening Kit, Beyond Technology, TX,USA ); no treatment for control group. All the discs were kept in sterile human saliva for 3.5 hours, and then the mixture of brain heart infusion broth (BHI) medium and Streptococcus mutans were added. The discs and Streptococcus mutans were incubated together in BHI medium with 5% CO(2) (volume fraction), at 37 °C. After 3, 7, 14, 21 and 28 d's incubation, two discs of each group were taken out and the biofilms on the enamel surfaces were evaluated by using conventional bacteria counts and confocal laser scanning microscope (CLSM). The bacteria in the biofilm on one disc enamel surface were analyzed by plating on BHIS agar and the colony-forming units were counted. The biofilm on the other disc surface was stained using a two-colour fluorescent dye kit (Bacerial Viability Kit L-7012) for CLSM. RESULTS: The vital bacteria counts of vital cells in the 3, 7, and 14 d's biofilms of the bleaching group were significantly fewer than those of the control group. Especially in the 3 days' biofilm on the whitened surface, the vital bacteria counts [(3 595 ± 2 903) µm(2) vs. (89 155 ± 65 963) µm(2),t = 8.71,P = 0.00] and proportion of vital bacteria [(26.0% ± 16.4%) vs.(92.2% ± 10.9%), t = 19.93, P = 0.00] were significantly fewer than those of the control. While, for the 21d's biofilm, the vital bacteria counts and the percentage of the vital cells of the bleaching group were more than those of the control group significantly [(66 262 ± 23 772) µm(2) vs. (51 184 ± 20 502) µm(2), t = 2.59, P = 0.012]. CONCLUSION: The hydrogen peroxide-containing bleaching agent may inhibit the growth of Streptococcus mutans biofilm for about 3 weeks; but after 3 weeks, it seems that the bleached surface will increase the growth of biofilm. Whether the whitening therapy will increase caries susceptibility of the bleached surface needs further research.
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Biopelículas/efectos de los fármacos , Esmalte Dental/microbiología , Peróxido de Hidrógeno/química , Streptococcus mutans/efectos de los fármacos , Blanqueamiento de Dientes , HumanosRESUMEN
Soil salinization poses a critical problem, adversely affecting plant development and sustainable agriculture. Plants can produce soil legacy effects through interactions with the soil environments. Salt tolerance of plants in saline soils is not only determined by their own stress tolerance but is also closely related to soil legacy effects. Creating positive soil legacy effects for crops, thereby alleviating crop salt stress, presents a new perspective for improving soil conditions and increasing productivity in saline farmlands. Firstly, the formation and role of soil legacy effects in natural ecosystems are summarized. Then, the processes by which plants and soil microbial assistance respond to salt stress are outlined, as well as the potential soil legacy effects they may produce. Using this as a foundation, proposed the application of salt tolerance mechanisms related to soil legacy effects in natural ecosystems to saline farmlands production. One aspect involves leveraging the soil legacy effects created by plants to cope with salt stress, including the direct use of halophytes and salt-tolerant crops and the design of cropping patterns with the specific crop functional groups. Another aspect focuses on the utilization of soil legacy effects created synergistically by soil microorganisms. This includes the inoculation of specific strains, functional microbiota, entire soil which legacy with beneficial microorganisms and tolerant substances, as well as the application of novel technologies such as direct use of rhizosphere secretions or microbial transmission mechanisms. These approaches capitalize on the characteristics of beneficial microorganisms to help crops against salinity. Consequently, we concluded that by the screening suitable salt-tolerant crops, the development rational cropping patterns, and the inoculation of safe functional soils, positive soil legacy effects could be created to enhance crop salt tolerance. It could also improve the practical significance of soil legacy effects in the application of saline farmlands.
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The utilization of Cobalt (Co) has surged due to it is critical role in renewable energy technologies and other high-tech applications. Concurrently, the potential health risks associated with Co exposure have raised concerns. Previous studies, including our own, have shown that Co can impair learn and memory functions as an epigenetic hazard, even at low concentrations. In this study, we explore the mechanisms of Co-induced ferroptosis in neurodegenerative damage both in vivo and in vitro, focusing on the epigenetic regulation by N6-methyladenosine (m6A) demethylase alkB homolog 5 (ALKBH5). We identify heme oxygenase-1 (HO-1) as a direct target gene of ALKBH5, playing a crucial role in mitigating Co-induced ferroptosis. ALKBH5 deficiency affects the post-transcriptional regulation of HO-1 through m6A modification, which in turn influences mRNA's stability, intracellular distribution, and alternative splicing, thereby enhancing susceptibility to Co-induced ferroptosis. Additionally, we discuss the potential involvement of heterogeneous nuclear ribonucleoprotein M (hnRNPM) in regulating alternative splicing of HO-1 mRNA, potentially mediated by m6A modifications. This study provides new epigenetic insights into the post-transcriptional regulatory mechanisms involved in Co-induced ferroptosis and highlights the broader implications of environmental hazards in neurodegenerative damage.
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Adenosina , Desmetilasa de ARN, Homólogo 5 de AlkB , Cobalto , Ferroptosis , Hemo-Oxigenasa 1 , ARN Mensajero , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Desmetilasa de ARN, Homólogo 5 de AlkB/metabolismo , Desmetilasa de ARN, Homólogo 5 de AlkB/genética , Animales , Ferroptosis/efectos de los fármacos , Adenosina/análogos & derivados , Adenosina/metabolismo , Cobalto/toxicidad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratones , Humanos , Enfermedades Neurodegenerativas/inducido químicamente , Enfermedades Neurodegenerativas/genética , Epigénesis GenéticaRESUMEN
Gut symbiotic bacteria are known to be closely related to insect development, nutrient metabolism, and disease resistance traits, but the most important factors leading to changes in these communities have not been well clarified. To address this, we examined the associations between the gut symbiotic bacteria and the host genotype and geographical distribution of Solenopsis invicta in China, where it is invasive and has spread primarily by human-mediated dispersal. Thirty-two phyla were detected in the gut symbiotic bacteria of S. invicta. Proteobacteria were the most dominant group among the gut symbiotic bacteria. Furthermore, the Bray-Curtis dissimilarity matrices of the gut symbiotic bacteria were significantly positively correlated with the geographical distance between the host ant colonies, but this relationship was affected by the social form. The distance between monogyne colonies had a significant effect on the Bray-Curtis dissimilarity matrices of gut symbiotic bacteria, but the distance between polygyne colonies did not. Moreover, the Bray-Curtis dissimilarity matrices were positively correlated with Nei's genetic distance of the host but were not correlated with the COI-based genetic distance. This study provides a scientific basis for further understanding the ecological adaptability of red imported fire ants during invasion and dispersal. IMPORTANCE We demonstrated that gut microbiota composition and diversity varied among populations. These among-population differences were associated with host genotype and geographical distribution. Our results suggested that population-level differences in S. invicta gut microbiota may depend more on environmental factors than on host genotype.
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Hormigas , Microbioma Gastrointestinal , Animales , Humanos , Hormigas/genética , Hormigas/microbiología , Microbioma Gastrointestinal/genética , Bacterias/genética , Proteobacteria/genética , GenotipoRESUMEN
AIM: The aim of the study was to investigate the effect of perceived social support (PSS) on sleep quality in arteriosclerotic obliterans patients in China and examined whether psychological flexibility (PF) has a mediating effect between PSS and sleep quality. DESIGN: A cross-sectional survey. METHODS: A cross-sectional study was conducted between September 2020 and December 2021 on 172 patients with atherosclerotic obliterans recruited from a hospital in China. RESULTS: PSS was negatively associated with sleep quality and PF, whereas PF was positively associated with sleep quality. This relationship between PSS and sleep quality was mediated by PF. PATIENT OR PUBLIC CONTRIBUTION: Vascular surgery specialist nurses assisted the members of the research group in distributing the questionnaires after the patients gave oral informed consent, and the patients cooperated to complete the questionnaires. We thank both parties for their contributions to this survey.
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Calidad del Sueño , Apoyo Social , Humanos , Estudios Transversales , Encuestas y Cuestionarios , ChinaRESUMEN
Background: Recent studies have reported that gut microbiota is closely associated with cognitive fuction. Fecal microbiota transplantation (FMT) may be a potential treatment for cognitive impairment, but its efficacy in patients with cognitive impairment is unknown. Objectives: This study aimed to investigate the safety and efficacy of FMT for cognitive impairment treatment. Methods: Five patients aged 54-80 years (three women) were enrolled in this single-arm clinical trial from July 2021 to May 2022. The Montreal Cognitive Assessment-B (MoCA-B), Activities of Daily Living (ADL), and the cognitive section of the Alzheimer's Disease Assessment Scale (ADAS-Cog) were assessed at days 0, 30, 60, 90, and 180. Additionally, stool and serum samples were obtained twice before FMT was administered and six months after the treatment. The structure of fecal microbiota was analyzed by 16S RNA gene sequencing. Serum samples were analyzed for metabolomics and lipopolysaccharide (LPS)-binding proteins by liquid chromatography-mass spectrometry and enzyme-linked immunosorbent assay, respectively. Safety was assessed based on adverse events, vital signs, and laboratory parameters during FMT and the follow-up period. Results: The MoCA, ADL, and ADAS-Cog scores of patients with mild cognitive impairment (patients C and E) after FMT were improved or maintained compared with those before transplantation. However, patients with severe cognitive impairment (patients A, B, and D) had no worsening of cognitive scores. Fecal microbiota analysis showed that FMT changed the structure of gut microbiota. The results of serum metabolomics analysis suggested that there were significant changes in the serum metabolomics of patients after FMT, with 7 up-regulated and 28 down-regulated metabolites. 3b,12a-dihydroxy-5a-cholanoic acid, 25-acetylvulgaroside, deoxycholic acid, 2(R)-hydroxydocosanoic acid, and P-anisic acid increased, while bilirubin and other metabolites decreased. KEFF pathway analysis indicated that the main metabolic pathways were bile secretion and choline metabolism in cancer. No adverse effects were reported throughout the study. Conclusions: In this pilot study, FMT could maintain and improve cognitive function in mild cognitive impairment by changing gut microbiota structure and affecting serum metabolomics. Fecal bacteria capsules were safe. However, further studies are needed to evaluate the safety and efficacy of fecal microbiota transplantation. ClinicalTrials.gov Identifier: CHiCTR2100043548.