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The mitochondrial electron transport chain (ETC) of apicomplexan parasites differs considerably from the ETC of the animals that these parasites infect, and is the target of numerous anti-parasitic drugs. The cytochrome c oxidase complex (Complex IV) of the apicomplexan Toxoplasma gondii ETC is more than twice the mass and contains subunits not found in human Complex IV, including a 13 kDa protein termed TgApiCox13. TgApiCox13 is homologous to a human iron-sulfur (Fe-S) cluster-containing protein called the mitochondrial inner NEET protein (HsMiNT) which is not a component of Complex IV in humans. Here, we establish that TgApiCox13 is a critical component of Complex IV in T. gondii, required for complex activity and stability. Furthermore, we demonstrate that TgApiCox13, like its human homolog, binds two Fe-S clusters. We show that the Fe-S clusters of TgApiCox13 are critical for ETC function, having an essential role in mediating Complex IV integrity. Our study provides the first functional characterisation of an Fe-S protein in Complex IV.
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Parásitos , Toxoplasma , Animales , Humanos , Toxoplasma/metabolismo , Parásitos/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Membranas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismoRESUMEN
Polycomb repressive complex 2 (PRC2), which mediates the deposition of H3K27me3 histone marks, is important for developmental decisions in animals and plants. In the shoot apical meristem (SAM), Three Amino acid Loop Extension family KNOTTED-LIKE HOMEOBOX /BEL-like (KNOX/BELL) transcription factors are key regulators of meristem cell pluripotency and differentiation. Here, we identified a PRC2-associated coiled-coil protein (PACP) that interacts with KNOX/BELL transcription factors in rice (Oryza sativa) shoot apex cells. A loss-of-function mutation of PACP resulted in differential gene expression similar to that observed in PRC2 gene knockdown plants, reduced H3K27me3 levels, and reduced genome-wide binding of the PRC2 core component EMF2b. The genomic binding of PACP displayed a similar distribution pattern to EMF2b, and genomic regions with high PACP- and EMF2b-binding signals were marked by high levels of H3K27me3. We show that PACP is required for the repression of cell differentiation-promoting genes targeted by a rice KNOX1 protein in the SAM. PACP is involved in the recruitment or stabilization of PRC2 to genes targeted by KNOX/BELL transcription factors to maintain H3K27me3 and gene repression in dividing cells of the shoot apex. Our results provide insight into PRC2-mediated maintenance of H3K27me3 and the mechanism by which KNOX/BELL proteins regulate SAM development.
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Oryza , Complejo Represivo Polycomb 2 , Animales , Diferenciación Celular/genética , Genes Homeobox , Histonas/genética , Histonas/metabolismo , Meristema/metabolismo , Oryza/metabolismo , Complejo Represivo Polycomb 2/genética , Complejo Represivo Polycomb 2/metabolismoRESUMEN
Pulmonary arterial hypertension (PAH) is a chronic disease characterized by pulmonary vascular remodeling. It refers to the abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs), and hypoxia is an important risk factor for this progression. The present study aims to investigate the role of YTHDF1 in the regulation of hypoxic PASMC proliferation and the underlying mechanism. Human PASMCs were transfected with si-YTHDF1/2/3 followed by treatment of hypoxia, and the PASMC proliferation and Foxm1 expression were detected. Through RNA pull-down, RNA immunoprecipitation, and protein synthesis assay, the mechanism of YTHDF1 regulating Foxm1 was explored. Next, Foxm1 was inhibited by thiostrepton, and cell proliferation was detected. In vivo, mice received a tail vein injection of adenovirus containing si-YTHDF1 and were exposed to hypoxia treatment. Pulmonary vascular changes, right ventricular systolic pressure (RVSP), and genes involving proliferation were analyzed. YTHDF1 silencing reduced more hypoxic PASMC proliferation and Foxm1 protein level than YTHDF2/3 silencing. Mechanical results showed that YTHDF1 interacted with Foxm1 mRNA and up-regulated Foxm1 protein level by enhancing the translation efficiency in an m6A-dependent manner. Furthermore, YTHDF1 facilitated hypoxic PASMC proliferation and proliferation marker expressions through up-regulation of Foxm1 in an m6A-dependent manner. In vivo, the YTHDF1 silencing alleviated pulmonary vascular changes and fibrosis, reduced RVSP, inhibited the interaction of YTHDF1 and Foxm1, and reduced proliferation marker levels, as compared to the PAH group. In conclusion, YTHDF1 silencing inhibits hypoxic PASMC proliferation by regulating Foxm1 translation in an m6A-dependent manner.
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Animales , Humanos , Ratones , Proliferación Celular , Células Cultivadas , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Factores de Transcripción Forkhead/metabolismo , Hipertensión Pulmonar/metabolismo , Hipoxia/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Hipertensión Arterial Pulmonar/metabolismo , Arteria Pulmonar/metabolismo , ARN/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
BACKGROUND: In China, the effects of heavy metals and metalloids (HMMs) on liver health are not consistently documented, despite their prevalent environmental presence. OBJECTIVE: Our research assessed the association between HMMs and liver function biomarkers in a comprehensive sample of Chinese adults. METHODS: We analyzed data from 9445 participants in the China National Human Biomonitoring survey. Blood and urine were evaluated for HMM concentrations, and liver health was gauged using serum albumin (ALB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) metrics. Various statistical methods were employed to understand the relationship between 11 HMMs and liver function, adjusting for multiple factors. We also explored interactions with alcohol intake, gender, and age. RESULTS: Among HMMs, selenium in blood [weighted geometric mean (GM) = 95.56 µg/L] and molybdenum in urine (GM = 46.44 µg/L) showed the highest concentrations, while lead in blood (GM = 21.92 µg/L) and arsenic in urine (GM = 19.80 µg/L) had the highest levels among risk HMMs. Manganese and thallium consistently indicated potential risk factor to liver in both sample types, while selenium displayed potential liver protection. Blood HMM mixtures were negatively associated with ALB (ß = -0.614, 95% CI: -0.809, -0.418) and positively with AST (ß = 0.701, 95% CI: 0.290, 1.111). No significant associations were found in urine HMM mixtures. Manganese, tin, nickel, and selenium were notable in blood mixture associations, with selenium and cobalt being significant in urine. The relationship of certain HMMs varied based on alcohol consumption. CONCLUSION: This research highlights the complex relationship between HMM exposure and liver health in Chinese adults, particularly emphasizing metals like manganese, thallium, and selenium. The results suggest a need for public health attention to low dose HMM exposure and underscore the potential benefits of selenium for liver health. Further studies are essential to establish causality.
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Exposición a Riesgos Ambientales , Contaminantes Ambientales , Hígado , Metaloides , Metales Pesados , Humanos , China , Masculino , Femenino , Adulto , Estudios Transversales , Persona de Mediana Edad , Metales Pesados/orina , Metales Pesados/sangre , Metaloides/orina , Metaloides/sangre , Metaloides/análisis , Hígado/efectos de los fármacos , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/orina , Contaminantes Ambientales/sangre , Adulto Joven , Anciano , Pruebas de Función Hepática , Pueblos del Este de AsiaRESUMEN
OBJECTIVE: To study the value of high-quality care in operating room during operation of patients with rectal cancer and the effect of this nursing model on postoperative rehabilitation. METHODS: This study recruited 72 patients with rectal cancer, including 36 in the control group and 36 in the observation group. Patients in the control group received routine care, and those in the observation group received high-quality care in operating room. RESULTS: The anxiety score (5.50 ± .77 vs 10. 08 ± 1.13), stress score (6.97 ± .60 vs 8.61 ± .99), and depression score (4.02 ± .65 vs 5.50 ± .91) in the observation group were less than the control group after treatment (P < .05). The measured values of diastolic blood pressure (73.19 ± 1.96 vs 86.13 ± 2.0), systolic blood pressure (121.08 ± 1.62 vs 130.63 ± 2.84), heart rate (73.05 ± 1.63 vs 87.11 ± 2.91) and adrenaline E(E) (58.40 ± 3.02 vs 61.42 ± 3.86) in the observation group were less than the control group after treatment (P < .05). The cooperation degree (94.44 vs 75.00) in the observation group was greater than the control group, but the operation time (308.47 ± 9.92 vs 339.47 ± 12.70), postoperative intestinal function recovery time (16.30 ± 1.14 vs 30.94 ± 2.10) and length of stay (10.47 ± 1.85 vs 13.33 ± 1.95) were all shorter than the control group (P < .05). The nasopharyngeal temperature in the observation group was greater than the control group at 30 minutes during operation (36.16 ± .50 vs 35.19 ± .40) and after operation, and fear score (2.22 ± .42 vs 3.63 ± .72) was less than the control group (P < .05). CONCLUSION: The application of high-quality care in the operating room during rectal cancer surgery has a significantly good clinical outcome.
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Neoplasias del Recto , Humanos , Neoplasias del Recto/cirugía , Femenino , Masculino , Persona de Mediana Edad , Quirófanos/normas , Anciano , Adulto , Complicaciones Posoperatorias , Cuidados Posoperatorios/normasRESUMEN
Fruit color is an intuitive quality of horticultural crops that can be used as an evaluation criterion for fruit ripening and is an important factor affecting consumers' purchase choices. In this study, a genetic population from the cross of green peel 'Qidong' and purple peel '8 guo' revealed that the purple to green color of eggplant peel is dominant and controlled by a pair of alleles. Bulked segregant analysis (BSA), SNP haplotyping, and fine genetic mapping delimited candidate genes to a 350 kb region of eggplant chromosome 10 flanked by markers KA2381 and CA8828. One ANS gene (EGP22363) was predicted to be a candidate gene based on gene annotation and sequence alignment of the 350-kb region. Sequence analysis revealed that a single base mutation of 'T' to 'C' on the exon green peel, which caused hydrophobicity to become hydrophilic serine, led to a change in the three-level spatial structure. Additionally, EGP22363 was more highly expressed in purple peels than in green peels. Collectively, EGP22363 is a strong candidate gene for anthocyanin biosynthesis in purple eggplant peels. These results provide important information for molecular marker-assisted selection in eggplants, and a basis for analyzing the regulatory pathways responsible for anthocyanin biosynthesis in eggplants.
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Antocianinas , Mapeo Cromosómico , Frutas , Solanum melongena , Solanum melongena/genética , Solanum melongena/metabolismo , Antocianinas/biosíntesis , Antocianinas/genética , Frutas/genética , Frutas/metabolismo , Pigmentación/genética , Polimorfismo de Nucleótido Simple , Genes de Plantas , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
OBJECTIVE: To systematically evaluate the current status of apathy in dementia patients and its associated factors. METHODS: We searched Chinese and English databases to collect studies on the associated factors of apathy in patients with dementia from inception to March 14, 2023. Two researchers independently screened the literature, evaluated the quality, and extracted the data RESULTS: A total of 20 studies were included, and the incidence of apathy in patients with dementia ranged from 21 % to 90 %. According to the model of apathy proposed by Massimo in 2018, the associated factors were divided into individual factors for dementia patients, caregiver factors, and environmental factors. The individual factors of apathy in patients with dementia mainly include demographic characteristics, the severity of cognitive impairment, a combination of other behavioral and psychological symptoms of dementia, acute medical problems or adverse drug reactions, unmet needs, and malnutrition. Caregiver factors mainly include emotional expressions of hostility or criticism towards dementia patients and caregivers' expectations for a better life in the future. Environmental factors mainly include too high or too low stimulation and a lack of daytime activities CONCLUSIONS: Existing studies have shown that the incidence of apathy in dementia patients is high and is affected by multi-dimensional factors. There are more studies on individual factors in dementia patients and fewer studies on caregivers and environmental factors. In the future, a large number of high-quality studies are needed to demonstrate the mechanism of apathy in dementia patients and to find more related factors.
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Apatía , Cuidadores , Demencia , Humanos , Demencia/psicología , Cuidadores/psicología , IncidenciaRESUMEN
Fine roots and leaves, the direct interfaces of plants with their external environment along the soil-plant-atmosphere continuum, are at the front line to ensure plant adaptation to their growing habitat. This study aimed to compare the vulnerability to water deficit of fine roots and leaves of woody species from karst and mangrove forests-two water-stressed habitats-against that of timber and ornamental woody species grown in a well-watered common garden. Thus, pressure-volume curves in both organs of 37 species (about 12 species from each habitat) were constructed. Fine roots wilted at a less negative water potential than leaves in 32 species and before branch xylem lost 50% of its hydraulic conductivity in the 17 species with available data on branch xylem embolism resistance. Thus, turgor loss in fine roots can act as a hydraulic fuse mechanism against water stress. Mangroves had higher leaf resistance against wilting and lower leaf-specific area than the karst and common garden plants. Their fine roots had high specific root lengths (SRL) and high capacitance to buffer water stress. Karst species had high leaf bulk modulus, low leaf capacitance, and delayed fine root wilting. This study showed the general contribution of fine roots to the protection of the whole plant against underground water stress. Our findings highlight the importance of water storage in the leaves and fine roots of mangrove species and high tolerance to water deficit in the leaves of mangrove species and the fine roots of some karst species.
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Deshidratación , Hojas de la Planta , Xilema , Ecosistema , SueloRESUMEN
Polyploidization leads to novel phenotypes and is a major force in evolution. However, the relationship between the evolution of new traits and variations in the post-translational modifications (PTM) of proteins during polyploidization has not been studied. Acetylation of lysine residues is a common protein PTM that plays a critical regulatory role in central metabolism. To test whether changes in metabolism in citrus fruit is associated with the reprogramming of lysine acetylation (Kac) in non-histone proteins during allotetraploidization, we performed a global acetylome analysis of fruits from a synthetic allotetraploid citrus and its diploid parents. A total of 4,175 Kac sites were identified on 1,640 proteins involved in a wide range of fruit traits. In the allotetraploid, parental dominance (i.e. resemblance to one of the two parents) in specific fruit traits, such as fruit acidity and flavonol metabolism, was highly associated with parental Kac level dominance in pertinent enzymes. This association is due to Kac-mediated regulation of enzyme activity. Moreover, protein Kac probably contributes to the discordance between the transcriptomic and proteomic variations during allotetraploidization. The acetylome reprogramming can be partially explained by the expression pattern of several lysine deacetylases (KDACs). Overexpression of silent information regulator 2 (CgSRT2) and histone deacetylase 8 (CgHDA8) diverted metabolic flux from primary metabolism to secondary metabolism and partially restored a metabolic status to the allotetraploid, which expressed attenuated levels of CgSRT2 and CgHDA8. Additionally, KDAC inhibitor treatment greatly altered metabolism in citrus fruit. Collectively, these findings reveal the important role of acetylome reprogramming in trait evolution during polyploidization.
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Citrus , Proteómica , Lisina/metabolismo , Proteoma/genética , Proteoma/metabolismo , Frutas/metabolismo , Citrus/genética , Citrus/metabolismo , Acetilación , Procesamiento Proteico-PostraduccionalRESUMEN
BACKGROUND: Glioma is the most malignant primary brain tumor with a poor survival time. The tumour microenvironment, especially glioma-associated microglia/macrophages (GAMs), plays an important role in the pathogenesis of glioma. Currently, microglia (CD11b+/CD45Low) and macrophages (CD11b+/CD45High) are distinguished as distinct cell types due to their different origins. Moreover, signal-transducing adaptor protein 1 (STAP1) plays a role in tumourigenesis and immune responses. However, to date, no studies have been reported on STAP1 in GAMs. METHODS: The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases were used to investigate the association between STAP1 mRNA levels and clinical parameters (grades, mutations in isocitrate dehydrogenase, and overall survival). RNA-sequencing, qRT-PCR, Western blotting, immunohistochemistry and immunofluorescence analyses were performed to detect the expression level of STAP1 and related proteins. BV-2 cells were used to construct a STAP1-overexpressing cell line. Phagocytosis of BV-2 cells was assessed by flow cytometry and fluorescence microscopy. C57BL/6 mice were used to establish orthotopic and subcutaneous glioma mouse models. Glioma growth was monitored by bioluminescence imaging. RESULTS: STAP1 expression in glioma-associated microglia is positively correlated with the degree of malignancy and poor prognosis of glioma. Moreover, STAP1 may promote M2-like polarisation by increasing ARG1 expression and inhibiting microglial phagocytosis of microglia. Increased ARG1 may be associated with the IL-6/STAT3 pathway. Impaired phagocytosis may be associated with decreased cofilin and filopodia. CONCLUSION: STAP1 is positively associated with the degree of glioma malignancy and may represent a potential novel therapeutic target for glioma.
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Neoplasias Encefálicas , Glioma , Ratones , Animales , Microglía , Línea Celular Tumoral , Ratones Endogámicos C57BL , Glioma/metabolismo , Macrófagos , Neoplasias Encefálicas/metabolismo , Microambiente TumoralRESUMEN
Herein, we propose a label-free chemiresistive sensor for the highly sensitive and selective detection of microcystin (MC)-LR in water samples. The sensor uses a layer-by-layer (LBL) assembled conductive film consisting of Ti3C2Tx nanosheets as the sensing channel. It is further modified by using an aptamer for the specific recognition of MC-LR. The response signal is based on the change in resistance of the conductive channel upon binding of MC-LR with the aptamer. Our novel strategy is the first concept proposed for immobilizing the aptamer containing -SH on the channel surface through a Ti-S bond under weakly alkaline condition. The resulting sensor is highly sensitive and stable for the detection of MC-LR, with a detection limit of 0.18 ng L-1 and a wide linear range from 1 to 104 ng L-1. We used the sensor to continuously monitor MC-LR released by cultivated Microcystis aeruginosa, showing a strong relationship between MC-LR and cell density. Furthermore, the sensor was successfully used to measure MC-LR in freshwater lakes with moderate algal blooms, and the results agreed well with those obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The present study provides a reliable method for highly sensitive and selective detection of MC-LR in environmental waters.
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Microcistinas , Espectrometría de Masas en Tándem , Microcistinas/análisis , Microcistinas/química , Cromatografía Liquida , Titanio , Lagos/análisis , Agua/químicaRESUMEN
Sixty Sprague-Dawley female rats were randomly divided into sham-operated groups and five ovariectomy (OVX) subgroups. Rats subjected to sham and OVX were treated with the vehicle, alendronate, and Zuogui Wan (ZGW) at the doses of low, medium and high lyophilized powder daily for 3 months, respectively. The gene or protein expression of NK1R, PPAR γ, and OSX were assayed by either quantitative polymerase chain reaction or Western blot analysis. The results showed that compared with the OVX group, ZGW could reduce the level of PPARγ and increase the levels of OSX and. Meanwhile, ZGW could prevent bone loss. In addition, we found ZGW upregulated for the NK1R mRNA or protein expression by promoting the expression level of transcription factor FoxO3 and increasing its binding to the NK1R promoter region -700/-200 sequence. These results suggest that the regulation of FoxO3 and NK1R played a role and contributed to the mechanism of ZGW underlying the increase in bone mass in the OVX rat model.
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Medicamentos Herbarios Chinos , Osteoporosis , Animales , Femenino , Ratas , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Osteoporosis/etiología , Osteoporosis/genética , Ovariectomía , Ratas Sprague-DawleyRESUMEN
Proteins existed in aquatic environments strongly influence the transport, fate of nanomaterials due to the formation of protein-corona surrounding nanomaterials. To date, how do proteins affect the aggregation behaviors of MXene, a new family of two-dimensional materials, in aquatic environment remains unknown. Here the aggregation kinetics of MXene Ti3C2Tx nanosheets in various electrolytes (NaCl, CaCl2 and Na2SO4) was investigated by time-resolved dynamic light scattering in absence or presence of bovine serum albumin (BSA). Results showed that BSA affected the aggregation of Ti3C2Tx in a concentration-dependent manner. Addition of 3 mg/L BSA decreased the critical coagulation concentrations (CCCs) of Ti3C2Tx about 1.6-2.1 times, showing obvious destabilization effect; while BSA greater than 30 mg/L created a high-protein environment covering Ti3C2Tx, producing high spatial repulsion and enhancing the dispersibility of Ti3C2Tx. Ca2+ ions have greater effect on the aggregation of Ti3C2Tx due to the larger surface charge and bridging effect. The interaction between Ti3C2Tx and BSA followed Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, and mainly attributed to hydrogen bonding and van der Waals forces, while positively charged lysine and arginine in BSA might attract onto Ti3C2Tx through electrostatic attraction. The interaction decreased the content of α-helix structure in BSA from 74.7% to 53.1%. Ti3C2Tx easily suffered from aggregation and their long-distance transport seemed impossible in synthetic or natural waters. The present findings provided new insights for understanding the transfer and fate of this nanomaterial in aquatic environments.
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Nanoestructuras , Corona de Proteínas , Cinética , TitanioRESUMEN
Although research into how spiders respond to cadmium (Cd)-induced toxicity is ongoing, little is known about the effects of Cd contamination on the exogenous microorganisms of spiders. The current study used 16 S rRNA gene sequencing to evaluate the richness and structure of external bacterial communities in the wolf spider Pardosa pseudoannulata under long- and short-term Cd stress. Our results showed that Proteobacteria and Acidibacter were the dominating bacterial phylum and genus. The alpha diversity analysis showed that the high background of Cd concentration (Cd) reduced bacterial alpha diversity, and short-term Cd (SCd) stress elevated bacterial richness and diversity. Hub bacterial genera, including Stenotrophobacter, Hymenobacter, Chitinophaga, and Bryobacter, were identified by co-occurrence network analysis and showed high connectance with other bacterial genera. Further investigation revealed 15 and 14 bacterial taxa that were classified distinctively under SCd and Cd stresses. Interestingly, functional prediction analysis showed that Cd stress enhanced some crucial pathways involved in specialized functions, including manganese oxidation and aromatic compound degradation. Random forest and correlation analyses found that the spider's molting time was the dominant driver affecting bacterial phyla (i.e., Proteobacteria and Planctomycetes) and genera (e.g., Acidibacter, Reyranella, and Haliangium). Collectively, this comprehensive analysis creates new perspectives to investigate the divergent responses of microbial communities in the spiders' external habitat under Cd stress, and provides valuable viewpoints for Cd pollution evaluation and control.
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Cadmio , Arañas , Animales , Cadmio/toxicidad , Oxidación-Reducción , Bacterias/genética , Contaminación Ambiental , Acidobacteria , ProteobacteriaRESUMEN
Epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells is critically involved in the occurrence of subretinal fibrosis. This study aimed to investigate the role of enhancer of zeste homolog 2 (EZH2) in EMT of human primary RPE cells and the underlying mechanisms of the anti-fibrotic effect of EZH2 suppression. Primary cultures of human RPE cells were treated with TGF-ß1 for EMT induction. EZH2 was silenced by siRNA to assess the expression levels of epithelial and fibrotic markers using qRT-PCR, Western blot, and immunofluorescence staining assay. Furthermore, the cellular migration, proliferation and barrier function of RPE cells were evaluated. RNA-sequencing analyses were performed to investigate the underlying mechanisms of EZH2 inhibition. Herein, EZH2 silencing up-regulated epithelial marker ZO-1 and downregulated fibrotic ones including α-SMA, fibronectin, and collagen 1, alleviating EMT induced by TGF-ß1 in RPE cells. Moreover, silencing EZH2 inhibited cellular migration and proliferation, but didn't affect cell apoptosis. Additionally, EZH2 suppression contributed to improved barrier functions after TGF-ß1 stimulation. The results from RNA sequencing suggested that the anti-fibrotic effect of EZH2 inhibition was associated with the MAPK signaling pathway, cytokine-cytokine receptor interaction, and the TGF-beta signaling pathway. Our findings provide evidence that the suppression of EZH2 might reverse EMT and maintain the functions of RPE cells. EZH2 could be a potential therapeutic avenue for subretinal fibrosis.
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Proteína Potenciadora del Homólogo Zeste 2 , Células Epiteliales , Transición Epitelial-Mesenquimal , Factor de Crecimiento Transformador beta1 , Proteína Potenciadora del Homólogo Zeste 2/genética , Células Epiteliales/metabolismo , Fibrosis , Humanos , Epitelio Pigmentado de la Retina/citología , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
Blood viscosity measurements are crucial for the diagnosis of cardiovascular and hematological diseases. Traditional blood viscosity measurements have obvious limitations because of their expensive equipment usage and large sample consumption. In this study, blood viscosity was measured by the oscillating circuit method and impedance analysis method based on single QCM. In addition, the effectiveness of two methods with high precision and less sample is proved by the experiments. Moreover, compared to the result from a standard rotational viscometer, the maximum relative errors of the proposed oscillating circuit method and impedance analysis method are ±5.2% and ±1.8%, respectively. A reliability test is performed by repeated measurement (N = 5), and the result shows that the standard deviation about 0.9% of impedance analysis is smaller than that of oscillating circuit method. Therefore, the impedance analysis method is superior. Further, the repeatability of impedance analysis method was evaluated by regression analysis method, and the correlation coefficient R2 > 0.965 demonstrated that it had excellent reproducibility.
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Viscosidad Sanguínea , Impedancia Eléctrica , Análisis de Regresión , Reproducibilidad de los ResultadosRESUMEN
Pre-mRNA processing factors (PRPFs) are vital components of the spliceosome and are involved in the physiological process necessary for pre-mRNA splicing to mature mRNA. As an important member, PRPF6 mutation resulting in autosomal dominant retinitis pigmentosa (adRP) is not common. Recently, we reported the establishment of an induced pluripotent stem cells (iPSCs; CSUASOi004-A) model by reprogramming the peripheral blood mononuclear cells of a PRPF6-related adRP patient, which could recapitulate a consistent disease-specific genotype. In this study, a disease model of retinal pigment epithelial (RPE) cells was generated from the iPSCs of this patient to further investigate the underlying molecular and pathological mechanisms. The results showed the irregular morphology, disorganized apical microvilli and reduced expressions of RPE-specific genes in the patient's iPSC-derived RPE cells. In addition, RPE cells carrying the PRPF6 mutation displayed a decrease in the phagocytosis of fluorescein isothiocyanate-labeled photoreceptor outer segments and exhibited impaired cell polarity and barrier function. This study will benefit the understanding of PRPF6-related RPE cells and future cell therapy.
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Células Madre Pluripotentes Inducidas , Retinitis Pigmentosa , Diferenciación Celular/genética , Células Epiteliales/metabolismo , Humanos , Leucocitos Mononucleares/metabolismo , Mutación , Precursores del ARN/metabolismo , Factores de Empalme de ARN/genética , Epitelio Pigmentado de la Retina/metabolismo , Pigmentos Retinianos/metabolismo , Retinitis Pigmentosa/metabolismo , Factores de Transcripción/metabolismoRESUMEN
In a healthy body, reactive oxygen species (ROS) and antioxidants remain balanced. When the balance is broken toward an overabundance of ROS, oxidative stress appears and may lead to oocyte aging. Oocyte aging is mainly reflected as the gradual decrease of oocyte quantity and quality. Here, we aim to review the relationship between oxidative stress and oocyte aging. First, we introduced that the defective mitochondria, the age-related ovarian aging, the repeated ovulation, and the high-oxygen environment were the ovarian sources of ROS in vivo and in vitro. And we also introduced other sources of ROS accumulation in ovaries, such as overweight and unhealthy lifestyles. Then, we figured that oxidative stress may act as the "initiator" for oocyte aging and reproductive pathology, which specifically causes follicular abnormally atresia, abnormal meiosis, lower fertilization rate, delayed embryonic development, and reproductive disease, including polycystic ovary syndrome and ovary endometriosis cyst. Finally, we discussed current strategies for delaying oocyte aging. We introduced three autophagy antioxidant pathways like Beclin-VPS34-Atg14, adenosine 5'-monophosphate (AMP)-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR), and p62-Keap1-Nrf2. And we also describe the different antioxidants used to combat oocyte aging. In addition, the hypoxic (5% O2 ) culture environment for oocytes avoiding oxidative stress in vitro. So, this review not only contribute to our general understanding of oxidative stress and oocyte aging but also lay the foundations for the therapies to treat premature ovarian failure and oocyte aging in women.
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Envejecimiento/fisiología , Oocitos/metabolismo , Estrés Oxidativo/fisiología , Reproducción/fisiología , Animales , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismoRESUMEN
To discover new mutants conferring enhanced tolerance to drought stress, we screened a mutagenized upland rice (Oryza sativa) population (cv. IAPAR9) and identified a mutant, named idr1-1 (increased drought resistance 1-1), with obviously increased drought tolerance under upland field conditions. The idr1-1 mutant possessed a significantly enhanced ability to tolerate high-drought stresses. Map-based cloning revealed that the gene LOC_Os05g26890, residing in the mapping region of IDR1 locus, carried a single-base deletion in the idr1-1 mutant. IDR1 encodes the Gα subunit of the heterotrimeric G protein (also known as RGA1), and this protein was localized in nucleus and to plasma membrane or cell periphery. Further investigations indicated that the significantly increased drought tolerance in idr1-1 mutants stemmed from a range of physiological and morphological changes, including greater leaf potentials, increased proline contents, heightened leaf thickness and upregulation of antioxidant-synthesizing and drought-induced genes, under drought-stressed conditions. Especially, reactive oxygen species (ROS) production might be remarkably impaired, while ROS-scavenging ability appeared to be markedly enhanced due to significantly elevated expression of ROS-scavenging enzyme genes in idr1-1 mutants under drought-stressed conditions. In addition, idr1-1 mutants showed reduced expression of OsBRD1. Altogether, these results suggest that mutation of IDR1 leads to alterations in multiple layers of regulations, which ultimately leads to changes in the physiological and morphological traits and limiting of ROS levels, and thereby confers obviously increased drought tolerance to the idr1-1 mutant.
Asunto(s)
Genes de Plantas/genética , Oryza/genética , Proteínas de Plantas/genética , Especies Reactivas de Oxígeno/metabolismo , Apoptosis , Cloroplastos/metabolismo , Clonación Molecular , Deshidratación , Genes de Plantas/fisiología , Mutación , Oryza/metabolismo , Oryza/fisiología , Estrés Oxidativo , Proteínas de Plantas/fisiología , TranscriptomaRESUMEN
Previous studies had demonstrated that in Arabidopsis, IDM3 is involved in ROS1-mediated DNA demethylation pathway, and SUVH-SDJ complex functions as a DNA methylation reader complex for enhancing gene transcription, which presumably recruits ROS1 to the promoters of target genes for DNA demethylation. Here, our analyses, however, showed that the IDM3 and SDJ1/2/3, the components of the SUVH-SDJ complex, are implicated in establishing and/or maintaining DNA methylation as well through DDR (DRD1-DMS3-RDM1) complex. idm3-3 or sdj1/2/3 mutations led to genome-wide DNA hypomethylation, and both mutants shared a large number of common hypo-DMRs (Differentially Methylated Regions) with rdm1-4 and dms3-4, suggesting that IDM3 and SDJ1/2/3 help establish and/or maintain DNA methylation, mediated by RdDM pathway, at a subset of genomic regions largely through DDR complex. IDM3 is able to strongly interact with RDM1 and DMS3, but weakly with SDJ1 and SDJ3; SDJ1 and SDJ3 is capable of interacting separately with RDM1 and DMS3. Furthermore, comparisons of DNA methylation features in idm3-3 and sdj1/2/3 indicated that idm3-3 and sdj1/2/3 mutations make differential impacts on DNA methylation levels and patterns on a genome-wide scale, indicating that they are targeted to quite distinct genomic regions for aiding in DNA methylation. Further analyses on ChIP-seq data demonstrated that RDM1, DMS3 and NRPE1 are enriched in IDM3- and SDJ1/2/3-targted regions. Altogether, our results provide clear demonstration that IDM3 and SDJ1/2/3 play a part in establishing and/or maintaining DNA methylation of a group of genomic regions, through the DDR complex.