RESUMO
The epithelial-mesenchymal transition (EMT) is a fundamental process in developing fibrotic diseases, including forming epiretinal membranes (ERMs). ERMs can result in irreversible vision loss. Previous research has demonstrated that vitreous (VIT) derived from patients with proliferative diabetic retinopathy can stimulate angiogenesis through the Axl/PI3K/Akt pathway. Building upon this knowledge, we aimed to explore the influence of VIT from patients with macular membranes in ARPE-19 cells. Our findings reveal that patient-derived VIT from individuals with macular membranes promotes EMT and phosphoinositide 3-kinase-delta (PI3Kδ) expression in ARPE-19 cells. To elucidate the function of PI3Kδ in the ERM, we conducted experiments involving the knockout of p110δ, a key subunit of PI3Kδ, and observed that its absence hinders EMT induced by patient-derived VIT. Moreover, p110δ depletion reduces cell proliferation and migration in ARPE-19 cells. Remarkably, these effects were further corroborated by applying the p110δ inhibitor idelalisib, which blocks fibrosis in the laser-induced fibrosis model. Collectively, our results propose that p110δ plays a critical role in the progression of ERMs. Consequently, targeting p110δ emerges as a promising therapeutic approach for mitigating fibrosis. These findings contribute to a better understanding of the underlying mechanisms involved in ERM formation and highlight the potential for p110δ-directed antifibrotic therapy in retinal diseases.
Assuntos
Doenças Retinianas , Vitreorretinopatia Proliferativa , Humanos , Transição Epitelial-Mesenquimal , Fibrose , Fosfatidilinositol 3-Quinases , Vitreorretinopatia Proliferativa/metabolismoRESUMO
This study introduces an innovative brain-targeted drug delivery system, RVG-Exo/CBD, utilizing rabies virus glycoprotein (RVG)-engineered exosomes for encapsulating cannabidiol (CBD). The novel delivery system was meticulously characterized, confirming the maintenance of exosomal integrity, size, and successful drug encapsulation with a high drug loading rate of 83.0 %. Evaluation of the RVG-Exo/CBD's brain-targeting capability demonstrated superior distribution and retention in brain tissue compared to unmodified exosomes, primarily validated through in vivo fluorescence imaging. The efficacy of this delivery system was assessed using a behavioral sensitization model in mice, where RVG-Exo/CBD notably suppressed methamphetamine-induced hyperactivity more effectively than CBD alone, indicating a reduction in effective dose and enhanced bioavailability. Overall, the RVG-Exo/CBD system emerges as a promising strategy for enhancing the therapeutic efficacy and safety of CBD, particularly for neurological applications, highlighting its potential for addressing the limitations associated with traditional CBD administration in clinical settings.
Assuntos
Encéfalo , Canabidiol , Canabidiol/administração & dosagem , Canabidiol/química , Canabidiol/farmacologia , Animais , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Camundongos , Masculino , Glicoproteínas/química , Glicoproteínas/metabolismo , Glicoproteínas/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Fragmentos de Peptídeos , Proteínas ViraisRESUMO
INTRODUCTION: Biomarkers are urgently required to identify peritoneal dialysis (PD) patients at risk of cardiovascular (CV) events. This study aimed to investigate the predictive value of soluble suppression of tumorigenicity-2 (sST2) for CV events in patients undergoing incident PD. METHODS: In this prospective cohort study, incident PD patients were enrolled. Blood samples to measure sST2 levels were obtained before PD catheter implantation. The patients underwent a standard peritoneal equilibration test (PET) after initiation of PD for 4-6 weeks. The sST2 levels in both serum and dialysate were determined using enzyme-linked immunosorbent assay. CV events were recorded during the follow-up period. RESULTS: A total of 137 patients were enrolled. During the follow-up period of 17.3 months, 49 (35.76%) patients experienced CV events. When patients were dichotomized based on the median values and the calculated cutoff values of sST2, the higher sST2 group had 2.980- and 3.048-fold increased risks of CV events, respectively, when compared with the lower sST2 group. Moreover, the prognostic value of sST2 remained significant as a continuous variable (per 1 standard deviation increase, hazard ratio [HR] = 1.037, 95% confidence interval [CI] 1.010-1.066, p = 0.008). N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were found to indicate a higher risk only when dichotomized based on the calculated cutoff values. Furthermore, serum sST2 and NT-proBNP levels simultaneously above the calculated cutoff values were associated with a higher risk of CV events (HR = 3.398, 95% CI 1.813-6.367, p < 0.001). CONCLUSION: Baseline serum sST2 level is an independent predictor of the risk of CV events in patients receiving incident PD, and in combination with NT-proBNP level, it can provide a more accurate predictive value.
Assuntos
Doenças Cardiovasculares , Proteína 1 Semelhante a Receptor de Interleucina-1 , Diálise Peritoneal , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Diálise Peritoneal/efeitos adversos , Estudos Prospectivos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/sangue , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Biomarcadores/sangue , Adulto , Prognóstico , Valor Preditivo dos TestesRESUMO
Plant height is an important agronomic trait that affects crop yield. Elucidating the molecular mechanism underlying plant height regulation is also an important question in developmental biology. Here, we report that a BELL transcription factor, ZmBELL10, positively regulates plant height in maize (Zea mays). Loss of ZmBELL10 function resulted in shorter internodes, fewer nodes, and smaller kernels, while ZmBELL10 overexpression increased plant height and hundred-kernel weight. Transcriptome analysis and chromatin immunoprecipitation followed by sequencing showed that ZmBELL10 recognizes specific sequences in the promoter of its target genes and activates cell division- and cell elongation-related gene expression, thereby influencing node number and internode length in maize. ZmBELL10 interacted with several other ZmBELL proteins via a spatial structure in its POX domain to form protein complexes involving ZmBELL10. All interacting proteins recognized the same DNA sequences, and their interaction with ZmBELL10 increased target gene expression. We identified the key residues in the POX domain of ZmBELL10 responsible for its protein-protein interactions, but these residues did not affect its transactivation activity. Collectively, our findings shed light on the functions of ZmBELL10 protein complexes and provide potential targets for improving plant architecture and yield in maize.
Assuntos
Perfilação da Expressão Gênica , Zea mays , Zea mays/genética , Zea mays/metabolismo , Ativação Transcricional/genética , Fenótipo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
OBJECTIVE: Pulmonary fibrosis (PF) is regarded as progressive lung disease. miR-155-5p depletion exerts anti-fibrotic effects in silicotic mice. This study explored the effect and possible mechanism of miR-155-5p in PF rats, hoping to find a new target for PF management. METHODS: Bleomycin-induced PF rat model was established. Alveolar structure and collagen fiber deposition were observed by HE and Elastica-Masson staining. Alveolitis and PF scores were evaluated using the method of Szapiel. Total collagen content was detected using the Sircol method. PF rats were intraperitoneally injected with NLRP3 inhibitor MCC950 or intravenously injected with miR-155-5p antagomir and si-FOXO3a lentivirus plasmids. Binding sites of miR-155-5p and FOXO3a were predicted using bioinformatics analysis and dual-luciferase reporter assay. The expressions of miR-155-5p, NLRP3, ASC, caspase-1, IL-1ß, IL-18, and FOXO3a were detected by RT-qPCR, Western blot, and ELISA. RESULTS: MCC950 treatment inhibited NLRP3 inflammasome, alleviated alveolar hemorrhage and alveolitis, and reduced blue collagen fiber deposition, scores of alveolitis and PF, and levels of NLRP3, ASC, caspase-1, IL-1ß, and IL-18 in PF rats. miR-155-5p was elevated in lung tissues of PF rats. Inhibition of miR-155-5p downregulated levels of NLRP3, ASC, caspase-1, IL-1ß, and IL-18 in lung tissues of PF rats. miR-155-5p targeted FOXO3a. miR-155-5p inhibition and silencing FOXO3a exacerbated alveolitis and PF in rats and increased levels of NLRP3, ASC, caspase-1, IL-1ß, and IL-18. CONCLUSIONS: miR-155-5p aggravated alveolitis and promoted PF by targeting FOXO3a and prompting the activation of NLRP3 inflammasome and then inducing IL-1ß and IL-18 release.
Assuntos
Proteína Forkhead Box O3 , MicroRNAs , Fibrose Pulmonar , Animais , Ratos , Caspase 1/metabolismo , Inflamassomos/metabolismo , Interleucina-18/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fibrose Pulmonar/induzido quimicamente , Sulfonamidas , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/metabolismoRESUMO
During urgent-start peritoneal dialysis (USPD) in end-stage renal disease (ESRD) patients, both adequate dialysis and skill training for fluid exchange are essential. However, automated peritoneal dialysis (APD) alone or manual fluid exchange peritoneal dialysis (MPD) alone could meet the above demands. Therefore, our study combined APD with MPD (A-MPD), and compared A-MPD with MPD, aiming to find the most appropriate treatment mode. This was a single-center, prospective, randomized controlled study. All eligible patients were randomized into the MPD and A-MPD groups. All patients underwent a five-day USPD treatment 48 h after catheter implantation, and they were followed up for six months after discharge. Overall, 74 patients were enrolled in this study. Among these, 14 and 60 patients quit due to complications during USPD and completed the study (A-MPD = 31, MPD = 29), respectively. Compared with MPD, the A-MPD treatment mode had a better effect on removing serum creatinine, blood urea nitrogen, and potassium and improving serum carbon dioxide combining power levels; it had less time expenditure on the fluid exchange by nurses (p < 0.05). In addition, patients in the A-MPD group had higher scores on the skill tests than those in the MPD group (p = 0.002). However, no significant differences in short-term peritoneal dialysis (PD) complications, PD technical survival rate, or mortality were found between the two groups. Therefore, the A-MPD mode could be recommended as an adoptable and suitable PD modality for USPD in the future.
Assuntos
Falência Renal Crônica , Diálise Peritoneal , Humanos , Estudos Prospectivos , Falência Renal Crônica/terapia , Diálise Renal , Nitrogênio da Ureia SanguíneaRESUMO
Metal-free carbon nanozymes could be promising with the unique features of intrinsic catalytic ability, structure diversity, and strong tolerance to acidic/alkaline media. However, to date, the study of metal-free carbon nanozymes fell far behind metal-based nanomaterials, in which, the majority reported much more peroxidase-like activity than other enzyme-mimicking behavior (e.g., oxidase). Thus, the exploit of high-performance carbon nanozymes is of importance but challenging. In this work, the nitrogen-rich conjugated polymer (Aza-CPs) with rigid network structure is utilized as precursor to yield N-doped carbon material QAU-Z1 in high yield via a direct pyrolysis method. Surprisingly, QAU-Z1 stood out in oxidase-like behavior, which significantly outperformed the control materials GNC-900 and QAU-Z2 with nucleobase or conjugated small molecule as precursor, respectively. More importantly, it is a crucial revelation that the catalytic performance is closely related to the change of zeta potential for carbon nanozyme during the substrate 3,3',5,5'-tetramethylbenzidine oxidation process, as well as its catalytical capacity to O2 , which could be insightful to understand the inherent mechanism. This work not only presents the potential of conjugated polymers in constructing highly efficient carbon nanozyme, but also reveals the vital role of interaction mode between the nanozyme and substrate in the catalytic performance.
Assuntos
Carbono , Nanoestruturas , Carbono/química , Catálise , Nitrogênio/química , Oxirredutases , PolímerosRESUMO
Maize (Zea mays) is an important cereal crop with suitable stalk formation which is beneficial for acquiring an ideal agronomic trait to resist lodging and higher planting density. The elongation pattern of stalks arises from the variable growth of individual internodes driven by cell division and cell expansion comprising the maize stalk. However, the spatiotemporal dynamics and regulatory network of the maize stalk development and differentiation process remain unclear. Here, we report spatiotemporally resolved transcriptomes using all internodes of the whole stalks from developing maize at the elongation and maturation stages. We identified four distinct groups corresponding to four developmental zones and nine specific clusters with diverse spatiotemporal expression patterns among individual internodes of the stalk. Through weighted gene coexpression network analysis, we constructed transcriptional regulatory networks at a fine spatiotemporal resolution and uncovered key modules and candidate genes involved in internode maintenance, elongation, and division that determine stalk length and thickness in maize. Further CRISPR/Cas9-mediated knockout validated the function of a cytochrome P450 gene, ZmD1, in the regulation of stalk length and thickness as predicted by the WGCN. Collectively, these results provide insights into the high genetic complexity of stalk development and the potentially valuable resources with ideal stalk lengths and widths for genetic improvements in maize.
Assuntos
Transcriptoma , Zea mays , Zea mays/genética , Transcriptoma/genética , Reprodução , Redes Reguladoras de Genes/genética , Grão Comestível , Regulação da Expressão Gênica de Plantas/genéticaRESUMO
In many higher plants, fatty acid (FA) biosynthesis is coordinately regulated at multiple levels by intricate regulatory networks. However, the factors and their regulatory mechanisms underlying seed oil accumulation are still limited. Here, we identified that loss of glycolytic metalloenzyme enolase2 (AtENO2) activity increased the contents of total FAs and salicylic acid (SA) but reduced the accumulation of flavonoids and mucilage by regulating the expression of key genes involved in their biosynthesis pathway in Arabidopsis thaliana seeds. AtENO2 physically interacts with the transcription factor AtTGA5, which may participate in the regulation of SA levels. Non-targeted metabolomics analysis of eno2- and WT also showed that the levels of three flavonoids, quercetin-3-galactoside, quercitrin, and epicatechin, were significantly decreased in eno2- , and the flavonoid biosynthesis pathway was also enriched in the KEGG analysis. Meanwhile, the mutation of AtENO2 delayed silique ripening, thereby prolonging silique photosynthesis time, allowing siliques to generate more photosynthesis products for FA biosynthesis. These results reveal a molecular mechanism by AtENO2 to regulate seed oil accumulation in A. thaliana, providing potential targets for improving crop seed oil quality.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Ácidos Graxos/metabolismo , Sementes/genética , Sementes/metabolismo , Flavonoides/metabolismo , Óleos de Plantas , Regulação da Expressão Gênica de PlantasRESUMO
Electrochemiluminescence (ECL) is one powerful tool in the sensing field, in which the electrochemical workstation is necessary to achieve the electrical/optical signal conversion in the presence of luminescent agents. By contrast, biofuel cells (BFCs) can also provide electricity from renewable biofuels under moderate conditions. More importantly, BFCs with the features of adjustable voltage output and excellent compatibility would well meet the requirement of working voltages for different ECL devices. However, to the best of our knowledge, the BFC-driven luminous system has not been reported. In this work, we constructed, for the first time, a BFC-driven ECL system with fast and stable signal outputs. To demonstrate the proof-of-concept of the BFC-ECL system, the sensitive and selective detection of histidine was achieved, exhibiting great potential among point-of-care diagnoses in remote regions. Overall, this work not only paves a new way for the conversion of chemical energy, electrical energy, and luminous system but also explores the new application of BFC.
Assuntos
Fontes de Energia Bioelétrica , Técnicas Biossensoriais , Substâncias Luminescentes , Técnicas Eletroquímicas , Medições LuminescentesRESUMO
The classic luminol-based electrochemiluminescence (ECL) platform generally suffers from self-decomposition of the coreactant (i.e., H2O2) during the reaction process, seriously hampering the luminous signal stability, as well as its practical application. To address this issue, apart from the introduction of complex exogenous species, preoxidation of the luminophore, and electrocatalysis for ECL signal amplification, we proposed a novel ECL model to realize the signal enhancement via in situ self-photocatalytic generation of the coreactant H2O2. Interestingly, the luminescence of luminol was simultaneously utilized as the light source to promote the conversation of O2 to H2O2 with the assistance of the photocatalyst resorcinol-formaldehyde resin, which could further improve the luminescence of luminol in turn. In comparison with the traditional case, this new ECL model not only exhibited obvious signal amplification but also efficiently boosted its stability of signal output. To sum up, an exogenous coreactant-free, highly stable ECL platform was obtained via simply integrating the photocatalyst RF and the luminol-based system. This work will not only inspire the design of a new integrated ECL system with a coreactant translator but also provide an ingenious insight for the construction of a new generation of ECL models.
Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Peróxido de Hidrogênio , Medições Luminescentes , LuminolRESUMO
Epigenetic modifications function in gene transcription, RNA metabolism, and other biological processes. However, multiple factors currently limit the scientific utility of epigenomic datasets generated for plants. Here, using deep-learning approaches, we developed a Smart Model for Epigenetics in Plants (SMEP) to predict six types of epigenomic modifications: DNA 5-methylcytosine (5mC) and N6-methyladenosine (6mA) methylation, RNA N6-methyladenosine (m6 A) methylation, and three types of histone modification. Using the datasets from the japonica rice Nipponbare, SMEP achieved 95% prediction accuracy for 6mA, and also achieved around 80% for 5mC, m6 A, and the three types of histone modification based on the 10-fold cross-validation. Additionally, > 95% of the 6mA peaks detected after a heat-shock treatment were predicted. We also successfully applied the SMEP for examining epigenomic modifications in indica rice 93-11 and even the B73 maize line. Taken together, we show that the deep-learning-enabled SMEP can reliably mine epigenomic datasets from diverse plants to yield actionable insights about epigenomic sites. Thus, our work opens new avenues for the application of predictive tools to facilitate functional research, and will almost certainly increase the efficiency of genome engineering efforts.
Assuntos
Aprendizado Profundo , Oryza , Metilação de DNA/genética , Epigênese Genética , Epigenômica , Genoma , Oryza/genéticaRESUMO
A novel and convenient method for the ratiometric fluorescence detection of alkaline phosphatase (ALP) activity was proposed based on dual emission of bovine serum albumin-templated gold nanoclusters (BSA-AuNCs) and the mechanism of the inner filter effect between BSA-AuNCs and p-nitrophenol (PNP). First, ALP catalyzed the hydrolysis of the substrate p-nitrophenyl phosphate (PNPP) to produce PNP. PNP effectively quenched the emission peak of BSA-AuNCs at 410 nm because of the overlap in absorbance feature of PNP and the fluorescence spectrum of BSA-AuNCs, and the peak at 650 nm was almost unaffected. Thus, a sensitive ratiometric method for detection of ALP activity was developed using the fluorescence intensity of BSA-AuNCs at 650 nm as a reference signal. ALP activity versus the ratio of fluorescence intensities at 410 and 650 nm showed good linearity between 0.2 and 5 mU mL-1 (R2 = 0.9931) and high sensitivity with a detection limit of 0.03 mU mL-1 (S/N = 3). The developed sensing method was successfully applied to investigate ALP inhibitors and detect ALP in serum samples.
Assuntos
Ouro , Nanopartículas Metálicas , Fosfatase Alcalina , Soroalbumina Bovina , Espectrometria de FluorescênciaRESUMO
BACKGROUND: Since the outbreak of COVID-19 in December 2019, it has spread rapidly and widely, bringing great psychological pressure to the public. In order to prevent the epidemic, traffic lockdown was required in many areas of China, which led to inconvenience of treatment for dialysis patients. This study was conducted to explore the psychological distress and the psychological demand induced by CO-VID-19 in the patients undergoing dialysis and compare the difference between hemodialysis (HD) and peritoneal dialysis (PD) patients during the traffic lockdown period. METHODS: Questionnaires were given to the dialysis patients in the West China Hospital of Sichuan University. The Impact of Event Scale (IES) was used to investigate the patients' trauma-related distress in response to COVID-19. RESULTS: 232 eligible respondents were enrolled in this cross-section study, consisting of 156 PD patients and 76 HD patients. The median IES score for all the enrolled patients was 8.00 (2.00-19.00), which belonged to the subclinical dimension of post-traumatic stress symptoms (PTSS). HD patients had a significant higher IES score than PD patients (11.50 vs. 8.00) (p < 0.05). HD patients already got more psychological support from the medical staff. According to IES scores, 22.4% HD patients and 13.4% PD patients were classified as having moderate or severe PTSS, which need psychological support (p < 0.05). But more patients of both groups considered psychological support was necessary (HD: 50%, PD: 45.5%) (p > 0.05). In the multivariate regression analysis, we found that dialysis vintage, the impact of COVID-19 on the severity of illness and daily life, and confidence in overcoming the disease contributed to IES score (p < 0.05). CONCLUSIONS: HD patients had more severe trauma-related stress symptoms than PD patients. When major public healthy events occurred, careful psychological estimate and sufficient psychological support should be provided to the dialysis patients, especially to the HD patients.
Assuntos
COVID-19/psicologia , Falência Renal Crônica/terapia , Angústia Psicológica , Sistemas de Apoio Psicossocial , Quarentena/psicologia , Diálise Renal/psicologia , SARS-CoV-2 , Transtornos de Estresse Pós-Traumáticos/etiologia , Atividades Cotidianas , Adulto , COVID-19/prevenção & controle , Estudos Transversais , Feminino , Necessidades e Demandas de Serviços de Saúde , Hemodiálise no Domicílio/psicologia , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/psicologia , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/psicologia , Relações Profissional-Paciente , Qualidade de Vida , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Inquéritos e Questionários , Centros de Atenção Terciária/estatística & dados numéricos , Índices de Gravidade do Trauma , Adulto JovemRESUMO
KEY MESSAGE: Epigenetic regulation has been implicated in the control of multiple agronomic traits in maize. Here, we review current advances in our understanding of epigenetic regulation, which has great potential for improving agronomic traits and the environmental adaptability of crops. Epigenetic regulation plays vital role in the control of complex agronomic traits. Epigenetic variation could contribute to phenotypic diversity and can be used to improve the quality and productivity of crops. Maize (Zea mays L.), one of the most widely cultivated crops for human food, animal feed, and ethanol biofuel, is a model plant for genetic studies. Recent advances in high-throughput sequencing technology have made possible the study of epigenetic regulation in maize on a genome-wide scale. In this review, we discuss recent epigenetic studies in maize many achieved by Chinese research groups. These studies have explored the roles of DNA methylation, posttranslational modifications of histones, chromatin remodeling, and noncoding RNAs in the regulation of gene expression in plant development and environment response. We also provide our future prospects for manipulating epigenetic regulation to improve crops.
Assuntos
Cromatina/metabolismo , Metilação de DNA , Epigênese Genética , Epigenômica/métodos , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Zea mays/genética , Cromatina/genética , Zea mays/crescimento & desenvolvimentoRESUMO
Amebiasis is a worldwide parasitic zoonosis, with symptoms of abdominal discomfort, indigestion, diarrhea, and even death. However, limited information about the prevalence of Entamoeba spp. in experimental nonhuman primates (NHPs) in southwestern China is available. The objective of the current study was to investigate the frequency and species identity of Entamoeba to evaluate potential zoonotic risk factors for Entamoeba spp. infection in experimental NHPs. A total of 505 fecal samples were collected from NHPs (macaques) and analyzed by PCR analysis the small subunit rRNA (SSU rRNA) gene of Entamoeba spp. Forty-seven specimens were positive for Entamoeba spp., and the prevalence of Entamoeba spp. was 9.31% (47/505). Significant differences in the prevalence rates among the three breeds (P = 0.002 < 0.01, df = 2, χ2 = 12.33) and feed types (P = 0.001 < 0.01, df = 1, χ2 = 10.12) were observed. Altogether, four Entamoeba species, including E. dispar (57.44%), E. chattoni (29.78%), E. histolytica (6.38%), and E. coli (6.38%), were identified by DNA sequence analysis. The results suggested a low prevalence but high diversity of Entamoeba species in experimental NHPs in Yunnan Province, southwestern China. Results of this study contribute to the knowledge of the genetic characteristics of Entamoeba spp. in NHPs.
Assuntos
Entamoeba/genética , Entamebíase/veterinária , Macaca/parasitologia , Infecções Protozoárias em Animais/epidemiologia , Infecções Protozoárias em Animais/parasitologia , Animais , Animais de Laboratório , China/epidemiologia , DNA de Protozoário/genética , Entamoeba/classificação , Entamoeba/isolamento & purificação , Entamebíase/epidemiologia , Entamebíase/parasitologia , Entamebíase/transmissão , Fezes/parasitologia , Epidemiologia Molecular , Prevalência , Infecções Protozoárias em Animais/transmissão , RNA Ribossômico/genética , Subunidades Ribossômicas Menores/genética , Análise de Sequência de DNARESUMO
Perception and transduction of salt stress signals are critical for plant survival, growth, and propagation. Thus, identification of components of the salt stress-signaling pathway is important for rice (Oryza sativa) molecular breeding of salt stress resistance. Here, we report the identification of an apetala2/ethylene response factor transcription factor INDETERMINATE SPIKELET1 (IDS1) and its roles in the regulation of rice salt tolerance. By genetic screening and phenotype analysis, we demonstrated that IDS1 conferred transcriptional repression activity and acted as a negative regulator of salt tolerance in rice. To identify potential downstream target genes regulated by IDS1, we conducted chromatin immunoprecipitation (ChIP) sequencing and ChIP-quantitative PCR assays and found that IDS1 may directly associate with the GCC-box-containing motifs in the promoter regions of abiotic stress-responsive genes, including LEA1 (LATE EMBRYOGENESIS ABUNDANT PROTEIN1) and SOS1 (SALT OVERLY SENSITIVE1), which are key genes regulating rice salt tolerance. IDS1 physically interacted with the transcriptional corepressor topless-related 1 and the histone deacetylase HDA1, contributing to the repression of LEA1 and SOS1 expression. Analyses of histone H3 acetylation status and RNA polymerase II occupation on the promoters of LEA1 and SOS1 further defined the molecular foundation of the transcriptional repression activity of IDS1. Our findings illustrate an epigenetic mechanism by which IDS1 modulates salt stress signaling as well as salt tolerance in rice.
Assuntos
Etilenos/metabolismo , Histona Desacetilases/metabolismo , Oryza/enzimologia , Reguladores de Crescimento de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Histona Desacetilases/genética , Oryza/genética , Oryza/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Tolerância ao Sal , Estresse Fisiológico , Fatores de Transcrição/genéticaRESUMO
Spatiotemporal regulation of transcription is fine-tuned at multiple levels, including chromatin compaction. Polycomb Repressive Complex 2 (PRC2) catalyzes the trimethylation of Histone 3 at lysine 27 (H3K27me3), which is the hallmark of a repressive chromatin state. Multiple PRC2 complexes have been reported in Arabidopsis thaliana to control the expression of genes involved in developmental transitions and maintenance of organ identity. Here, we show that PRC2 member genes display complex spatiotemporal gene expression patterns and function in root meristem and vascular cell proliferation and specification. Furthermore, PRC2 gene expression patterns correspond with vascular and nonvascular tissue-specific H3K27me3-marked genes. This tissue-specific repression via H3K27me3 regulates the balance between cell proliferation and differentiation. Using enhanced yeast one-hybrid analysis, upstream regulators of the PRC2 member genes are identified, and genetic analysis demonstrates that transcriptional regulation of some PRC2 genes plays an important role in determining PRC2 spatiotemporal activity within a developing organ.
Assuntos
Arabidopsis/metabolismo , Complexo Repressor Polycomb 2/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Complexo Repressor Polycomb 2/genética , Regiões Promotoras Genéticas/genéticaRESUMO
The highly-conserved Polycomb group (PcG) and trithorax group (trxG) proteins play major roles in regulating gene expression and maintaining developmental states in many organisms. However, neither the recruitment of Polycomb repressive complexes (PRC) nor the mechanisms of PcG and trxG-mediated gene silencing and activation are well understood. Recent progress in Arabidopsis research challenges the dominant model of PRC2-dependent recruitment of PRC1 to target genes. Moreover, evidence indicates that diverse forms of PRC1, with shared components, are a common theme in plants and mammals. Although trxG is known to antagonize PcG, emerging data reveal that trxG can also repress gene expression, acting cooperatively with PcG. We discuss these recent findings and highlight the employment of diverse epigenetic mechanisms during development in plants and animals.
Assuntos
Proteína de Leucina Linfoide-Mieloide/fisiologia , Proteínas do Grupo Polycomb/fisiologia , Animais , Arabidopsis/embriologia , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/fisiologia , Evolução Molecular , Histonas/metabolismo , Humanos , Proteína de Leucina Linfoide-Mieloide/química , Proteínas de Plantas , Proteínas do Grupo Polycomb/químicaRESUMO
BACKGROUND: Negative coronary artery remodeling is frequent in patients with diabetes, but its mechanism remains unclear. We here evaluated the association of serum levels of glycated albumin (GA) and endogenous secretory receptor for advanced glycation end products (esRAGE) with coronary artery remodeling in type 2 diabetic patients. METHODS: Serum levels of GA and esRAGE were measured and intravascular ultrasound was performed in 136 consecutive diabetic patients with 143 coronary intermediate lesions. The remodeling index (RI) was calculated as the ratio between external elastic membrane (EEM) area at the lesion site and EEM area at the reference segment. Negative remodeling (NR) was defined as an RI < 0.95 and intermediate or positive remodeling as an RI ≥ 0.95. RESULTS: Mean plaque burden at the lesion site was 70.96 ± 9.98%, and RI was 0.96 ± 0.18. Negative coronary arterial remodeling existed in 81 (56.6%) lesions. RI correlated closely with serum esRAGE level (r = 0.236, P = 0.005) and was inversely related to serum GA level (r = - 0.240, P = 0.004) and plasma low-density lipoprotein cholesterol (LDL-C) (r = - 0.206, P = 0.014) and total cholesterol levels (r = - 0.183, P = 0.028). Generalized estimating equations logistic regression analysis identified esRAGE (OR 0.037; 95% CI 0.012-0.564, P = 0.021), GA (OR 1.093; 95% CI 1.013-1.179, P = 0.018) and LDL-C (OR 1.479; 95% CI 1.072-2.835, P = 0.023) as independent predictors for negative remodeling. CONCLUSIONS: In diabetic patients, negative coronary artery remodeling is associated with increased GA and decreased esRAGE levels in serum.