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Hippo pathway is an evolutionarily conserved signaling pathway comprising a series of MST/LATS kinase complexes. Its key transcriptional coactivators YAP and TAZ regulate transcription factors such as TEAD family to direct gene expression. The regulation of Hippo pathway, especially the nuclear level change of YAP and TAZ, significantly influences the cell fate switching from proliferation to differentiation, regeneration, and postinjury repair. This review outlines the main findings of Hippo pathway in peripheral nerve development, regeneration, and tumorigenesis, especially the studies in Schwann cells. We also summarize other roles of Hippo pathway in damage repair of the peripheral nerve system and discuss the potential future research which probably contributes to novel therapeutic strategies.
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BACKGROUND: Charcot-Marie-Tooth disease 2C (CMT2C) and scapuloperoneal spinal muscular atrophy (SPSMA) are different clinical phenotypes of TRPV4 mutation. The mutation of p.R316C has been reported to cause CMT2C and SPSMA separately. CASE PRESENTATION: Here, we reported a Chinese family harboring the same p.R316C variant, but with an overlap syndrome and different clinical manifestations. A 58-year-old man presented with severe scapula muscle atrophy, resulting in sloping shoulders. He also exhibited distinct muscle atrophy in his four limbs, particularly in the lower limbs. The sural nerve biopsy revealed severe loss of myelinated nerve fibers with scattered regenerating clusters and pseudo-onion bulbs. Nerve conduction study showed axon damage in both motor and sensory nerves. Sensory nerve action potentials could not be evoked in bilateral sural or superficial peroneal nerves. He was diagnosed with Charcot-Marie-Tooth disease type 2C and scapuloperoneal muscular atrophy overlap syndrome, whereas his 27-year-old son was born with clubfoot and clinodactyly. Electromyogram examination indicated chronic neurogenic changes and anterior horn cells involvement. Although there was no obvious weakness or sensory symptoms, early SPSMA could be considered for him. CONCLUSIONS: A literature review of the clinical characteristics in CMT2C and SPSMA patients with TRPV4 mutation suggested that our case was distinct due to the overlap syndrome and phenotype variation. Altogether, this case broadened the phenotype spectrum and provided the nerve biopsy pathological details of TRPV4-related neuropathies.
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Doenças Autoimunes , Doença de Charcot-Marie-Tooth , Doenças do Tecido Conjuntivo , Atrofia Muscular Espinal , Humanos , Masculino , Doença de Charcot-Marie-Tooth/genética , Atrofia Muscular , Atrofia Muscular Espinal/genética , Canais de Cátion TRPV/genética , Pessoa de Meia-IdadeRESUMO
Tiller angle in cereals is a key shoot architecture trait that strongly influences grain yield. Studies in rice (Oryza sativa) have implicated shoot gravitropism in the regulation of tiller angle. However, the functional link between shoot gravitropism and tiller angle is unknown. Here, we conducted a large-scale transcriptome analysis of rice shoots in response to gravistimulation and identified two new nodes of a shoot gravitropism regulatory gene network that also controls rice tiller angle. We demonstrate that HEAT STRESS TRANSCRIPTION FACTOR 2D (HSFA2D) is an upstream positive regulator of the LAZY1-mediated asymmetric auxin distribution pathway. We also show that two functionally redundant transcription factor genes, WUSCHEL RELATED HOMEOBOX6 (WOX6) and WOX11, are expressed asymmetrically in response to auxin to connect gravitropism responses with the control of rice tiller angle. These findings define upstream and downstream genetic components that link shoot gravitropism, asymmetric auxin distribution, and rice tiller angle. The results highlight the power of the high-temporal-resolution RNA-seq data set and its use to explore further genetic components controlling tiller angle. Collectively, these approaches will identify genes to improve grain yields by facilitating the optimization of plant architecture.
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Ácidos Indolacéticos/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Oryza/genética , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
OBJECTIVE: To investigate the expression of IFN-λ1 in respiratory epithelial cells of children with respiratory syncytial virus (RSV) infection and its relationship with RSV load. METHODS: The nasopharyngeal swabs were collected from the children who were hospitalized with respiratory tract infection from June 2015 to June 2016. A direct immunofluorescence assay was used to detect the antigens of seven common respiratory viruses (including RSV) in the nasopharyngeal swabs. A total of 120 children who were only RSV positive were selected as the RSV infection group. A total of 50 children who had negative results in the detection of all viral antigens were selected as the healthy control group. Fluorescence quantitative real-time PCR was used to determine the RSV load and the expression of IFN-λ1 mRNA in the nasopharyngeal swabs of children in the two groups. RESULTS: The expression of IFN-λ1 in the RSV infection group was significantly higher than that in the healthy control group (P<0.05). The expression of IFN-λ1 was positively correlated with RSV load (r=0.56, P<0.05). CONCLUSIONS: RSV can induce the expression of IFN-λ1 in respiratory epithelial cells, suggesting that IFN-λ1 may play an important role in anti-RSV infection.
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Interleucinas/fisiologia , Infecções por Vírus Respiratório Sincicial/imunologia , Carga Viral , Antígenos Virais/análise , Pré-Escolar , Células Epiteliais/imunologia , Feminino , Humanos , Lactente , Recém-Nascido , Interferons , Interleucinas/análise , Masculino , Nasofaringe/microbiologia , Reação em Cadeia da Polimerase em Tempo Real , Infecções por Vírus Respiratório Sincicial/virologiaRESUMO
OBJECTIVE: To investigate the antigen clearance time, time to symptom disappearance, and the association between them using immunofluorescence assay for dynamic monitoring of influenza virus antigen in children with influenza. METHODS: A total of 1 063 children suspected of influenza who visited the Hunan People's Hospital from March to April, 2016 were enrolled. The influenza A/B virus antigen detection kit (immunofluorescence assay) was used for influenza virus antigen detection. The children with positive results were given oseltamivir as the antiviral therapy and were asked to re-examine influenza virus antigen at 5, 5-7, and 7 days after onset. RESULTS: Of all children suspected of influenza, 560 (52.68%) had an influenza virus infection. A total of 215 children with influenza virus infection were followed up. The clearance rate of influenza virus antigen was 9.8% (21 cases) within 5 days after onset. The cumulative clearance rate of influenza virus antigen was 32.1% (69 cases) within 5-7 days, and 98.1% (211 cases) within 7-10 days after onset. Among these children, 6 children (2.8%) achieved the improvement in clinical symptoms within 3 days after onset. The cumulative rate of symptom improvement was 84.7% (182 cases) within 3-5 days after onset, and 100% achieved the improvement after 5 days of onset. CONCLUSIONS: The time to improvement in symptoms after treatment is earlier than antigen clearance time. Almost all of the children achieve influenza virus antigen clearance 7-10 days after onset. Therefore, it is relatively safe for children to go back to school within 7-10 days after onset when symptoms disappear.
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Antígenos Virais/sangue , Vírus da Influenza A/imunologia , Vírus da Influenza B/imunologia , Criança , Pré-Escolar , Feminino , Imunofluorescência , Humanos , Lactente , Masculino , Fatores de TempoRESUMO
Background: Hereditary transthyretin amyloidosis (ATTRv; v for variant) with polyneuropathy is a rare, progressive, and fatal autosomal dominant disorder. Therapies such as liver transplantation and TTR stabilizations have limitations. Patisiran is a small interfering RNA (siRNA), offering potential as a genetic-level therapy for hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). However, evidence on patisiran's efficacy and safety for ATTRv-PN remains limited. Objectives: This study aimed to further clarify patisiran's efficacy and safety for ATTRv-PN by meta-analysis. Design: Systematic review and meta-analysis. Methods: After literature searches in PubMed, Ovid MEDLINE, Embase, JBI EBP, Cochrane, and ClinicalTrials.gov databases on 7 June 2024, 11 studies with 503 patients were included and clinical data were extracted. Results: Results showed an 88% (95% confidence interval (CI): 81%-94%) pooled responsiveness rate. The standardized mean difference of modified Neuropathy Impairment Score plus 7 nerve tests (mNIS + 7) scores was -0.18 (95% CI: -0.32 to -0.03, p-value 0.018) and Norfolk Quality of Life-Diabetic Neuropathy was -0.21 (95% CI: -0.35 to -0.08, p-value 0.002). In total, 413 adverse events (AEs) (84.8%), 158 serious AEs (32.4%), and 37 deaths (7.6%) were recorded. Most of AEs were mild to moderate. No deaths were attributed to patisiran. However, there is no statistically significant improvement in Neuropathy Impairment Scores. Conclusion: In conclusion, patisiran was effective and safe for patients with ATTRv-PN. More large-scale clinical trials and long-term studies are necessary to further validate patisiran's efficacy and safety. Trial registration: PROSPERO registration ID: CRD42023428838.
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As temperature serves as a versatile input signal, thermoresponsive genetic controls have gained significant interest for recombinant protein production and metabolic engineering applications. The conventional thermoresponsive systems normally require the continuous exposure of heat stimuli to trigger the prolonged expression of targeted genes, and the accompanied heat-shock response is detrimental to the bioproduction process. In this study, we present the design of thermoresponsive quorum-sensing (ThermoQS) circuits to make Escherichia coli record transient heat stimuli. By conversion of the heat input into the accumulation of quorum-sensing molecules such as acyl-homoserine lactone derived from Pseudomonas aeruginosa, sustained gene expressions were achieved by a minimal heat stimulus. Moreover, we also demonstrated that we reprogrammed the E. coli Lac operon to make it respond to heat stimuli with an impressive signal-to-noise ratio (S/N) of 15.3. Taken together, we envision that the ThermoQS systems reported in this study are expected to remarkably diminish both design and experimental expenditures for future metabolic engineering applications.
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Escherichia coli , Resposta ao Choque Térmico , Engenharia Metabólica , Pseudomonas aeruginosa , Percepção de Quorum , Escherichia coli/genética , Escherichia coli/metabolismo , Percepção de Quorum/genética , Resposta ao Choque Térmico/genética , Engenharia Metabólica/métodos , Pseudomonas aeruginosa/genética , Regulação Bacteriana da Expressão Gênica , Acil-Butirolactonas/metabolismoRESUMO
MOTIVATION: Microsatellites are among the most useful genetic markers in population biology. High-throughput sequencing of microsatellite-enriched libraries dramatically expedites the traditional process of screening recombinant libraries for microsatellite markers. However, sorting through millions of reads to distill high-quality polymorphic markers requires special algorithms tailored to tolerate sequencing errors in locus reconstruction, distinguish paralogous loci, rarify raw reads originating from the same amplicon and sort out various artificial fragments resulting from recombination or concatenation of auxiliary adapters. Existing programs warrant improvement. RESULTS: We describe a microsatellite prediction framework named HighSSR for microsatellite genotyping based on high-throughput sequencing. We demonstrate the utility of HighSSR in comparison to Roche gsAssembler on two Roche 454 GS FLX runs. The majority of the HighSSR-assembled loci were reliably mapped against model organism reference genomes. HighSSR demultiplexes pooled libraries, assesses locus polymorphism and implements Primer3 for the design of PCR primers flanking polymorphic microsatellite loci. As sequencing costs drop and permit the analysis of all project samples on next-generation platforms, this framework can also be used for direct simple sequence repeats genotyping. AVAILABILITY: http://code.google.com/p/highssr/
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Algoritmos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Animais , Borboletas/classificação , Borboletas/genética , Fungos/classificação , Fungos/genética , Biblioteca Gênica , Marcadores Genéticos , Genoma , Repetições de Microssatélites/genética , Família Multigênica , Plantas/genética , Polimorfismo Genético , Especificidade da EspécieRESUMO
OBJECTIVES: The purpose of this study was to evaluate the diagnostic value of quantitative magnetic resonance neurography (MRN) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We also compared various MRN parameters and determined the best performing one. METHODS: Through literature searches in PubMed, Embase, Cochrane, Ovid MEDLINE and ClinicalTtrials.gov until March 1, 2023, we selected studies with the diagnostic performance of MRN in CIDP patients. The pooled estimated sensitivity and specificity of quantitative MRN parameters were determined by a bivariate random-effects model. Subgroup analysis was performed to evaluate the proper quantitative parameters and nerve sites. RESULTS: A total of 14 quantitative MRN studies with 23 results gave a pooled sensitivity of 0.73 (95% CI 0.66-0.79) and a pooled specificity of 0.89 (95% CI 0.84-0.92). The area under the curve (AUC) was 0.89 (95%CI 0.86-0.92). Subgroup analysis of quantitative parameters showed the fractional anisotropy (FA) with the highest sensitivity of 0.85 (95% CI 0.77-0.90) and cross-sectional area (CSA) with the highest specificity of 0.95 (95% CI 0.85-0.99). The pooled correlation coefficient for interobserver agreements was 0.90 (95%CI 0.82-0.95). CONCLUSION: Quantitative MRN has considerable diagnostic value in CIDP patients with accuracy and reliability. FA and CSA can be promising parameters in the future diagnosis of CIDP patients. ADVANCES IN KNOWLEDGE: This is the first meta-analysis of quantitative MRN in the diagnosis of CIDP.We have selected reliable parameters with cut-off value and provided new insights for subsequent diagnosis of CIDP.
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Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Humanos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico por imagem , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Área Sob a Curva , Imageamento por Ressonância Magnética/métodosRESUMO
Bimetallic oxide is a potential catalyst for oxidative desulfurization of fuel. Thus, an appropriate method is needed to improve its catalytic performance. Manufacturing defect is an effective means. In this contribution, an oxygen vacancies (OVs) regulation strategy for enhancing the catalytic activity of bimetallic oxide is proposed. Density functional theory (DFT) calculations show that the crystal phase has a huge influence on the generation energy of oxygen vacancies, so a series of V-Nb mixed oxide with different crystal phases are synthesized. Detailed characterizations show that the as-prepared tetragonal V-Nb mixed oxide (T-VNbOx) has lower OVs formation energy and larger OVs concentration (compared to orthorhombic V-Nb mixed oxides, O-VNbOx). Owing to the activation of OVs, the catalytic activity of T-VNbOx was significantly enhanced to form ultra-deep oxidative desulfurization. In addition, T-VNbOx can be cycled eight times without significantly degrading the desulfurization performance.
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Similarity learning has been recognized as a crucial step for object tracking. However, existing multiple object tracking methods only use sparse ground truth matching as the training objective, while ignoring the majority of the informative regions in images. In this paper, we present Quasi-Dense Similarity Learning, which densely samples hundreds of object regions on a pair of images for contrastive learning. We combine this similarity learning with multiple existing object detectors to build Quasi-Dense Tracking (QDTrack), which does not require displacement regression or motion priors. We find that the resulting distinctive feature space admits a simple nearest neighbor search at inference time for object association. In addition, we show that our similarity learning scheme is not limited to video data, but can learn effective instance similarity even from static input, enabling a competitive tracking performance without training on videos or using tracking supervision. We conduct extensive experiments on a wide variety of popular MOT benchmarks. We find that, despite its simplicity, QDTrack rivals the performance of state-of-the-art tracking methods on all benchmarks and sets a new state-of-the-art on the large-scale BDD100K MOT benchmark, while introducing negligible computational overhead to the detector.
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Background: Opioid-induced hyperalgesia (OIH) is an adverse event of prolonged opioid use that increases pain intensity. The optimal drug to prevent these adverse effects is still unknown. We aimed to conduct a network meta-analysis to compare different pharmacological interventions for preventing the increase in postoperative pain intensity caused by OIH. Methods: Several databases were searched independently for randomized controlled trials (RCTs) comparing various pharmacological interventions to prevent OIH. The primary outcomes were postoperative pain intensity at rest after 24 h and the incidence of postoperative nausea and vomiting (PONV). Secondary outcomes included pain threshold at 24 h after surgery, total morphine consumption over 24 h, time to first postoperative analgesic requirement, and shivering incidence. Results: In total, 33 RCTs with 1711 patients were identified. In terms of postoperative pain intensity, amantadine, magnesium sulphate, pregabalin, dexmedetomidine, ibuprofen, flurbiprofen plus dexmedetomidine, parecoxib, parecoxib plus dexmedetomidine, and S (+)-ketamine plus methadone were all associated with milder pain intensity than placebo, with amantadine being the most effective (SUCRA values = 96.2). Regarding PONV incidence, intervention with dexmedetomidine or flurbiprofen plus dexmedetomidine resulted in a lower incidence than placebo, with dexmedetomidine showing the best result (SUCRA values = 90.3). Conclusion: Amantadine was identified as the best in controlling postoperative pain intensity and non-inferior to placebo in the incidence of PONV. Dexmedetomidine was the only intervention that outperformed placebo in all indicators. Clinical Trial Registration: https://www.crd.york.ac. uk/prospero/display_record.php?, CRD42021225361.
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Tyrosol is an aromatic compound with great value that is widely used in the food and pharmaceutical industry. In this study, we reported a synthetic pathway for converting p-coumaric acid (p-CA) into tyrosol in Escherichia coli. We found that the enzyme cascade comprising ferulic acid decarboxylase (FDC1) from Saccharomyces cerevisiae, styrene monooxygenase (SMO), styrene oxide isomerase (SOI) from Pseudomonas putida, and phenylacetaldehyde reductase (PAR) from Solanum lycopersicum could efficiently synthesize tyrosol from p-CA with a conversion rate over 90%. To further expand the range of substrates, we also introduced tyrosine ammonia-lyase (TAL) from Flavobacterium johnsoniae to connect the synthetic pathway with the endogenous l-tyrosine metabolism. We found that tyrosol could be efficiently produced from glycerol, reaching 545.51 mg/L tyrosol in a tyrosine-overproducing strain under shake flasks. In summary, we have established alternative routes for tyrosol synthesis from p-CA (a potential lignin-derived biomass), glucose, and glycerol.
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Escherichia coli , Álcool Feniletílico , Escherichia coli/genética , Escherichia coli/metabolismo , Engenharia Metabólica , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/metabolismo , Tirosina/metabolismoRESUMO
Marine sediments act as a sink for various heavy metals, which may have profound impact on sedimentary microbiota. However, our knowledge about the collaborative response of bacterial community to chronic heavy metal contamination remains little. In this study, concentrations of seven heavy metals (As, Cd, Cr, Cu, Hg, Pb, and Zn) in sediments collected from the East China Sea were analyzed and Illumina Miseq 16 S rRNA sequencing was applied to characterize the structure of bacterial community. Microbiota inhabiting sediments in the East China Sea polluted with heavy metals showed different community composition from relatively pristine sites. The response of bacterial community to heavy metal stress was further interrogated with weighted correlation network analysis (WGCNA). WGCNA revealed ten bacterial modules exhibiting distinct co-occurrence patterns and among them, five modules were related to heavy metal pollution. Three of them were positively correlated with an increase in at least one heavy metal concentration, hubs (more influential bacterial taxa) of which were previously reported to be involved in the geochemical cycling of heavy metals or possess tolerance to heavy metals, while another two modules showed opposite patterns. Our research suggested that ecological functional transition might have occurred in East China Sea sediments by shifts of community composition with sensitive modules majorly involved in the meaningful global biogeochemical cycling of carbon, sulfur, and nitrogen replaced by more tolerant groups of bacteria due to long-term exposure to low-concentration heavy metals. Hubs may serve as indicators of perturbations of benthic bacterial community caused by heavy metal pollution and support monitoring remediation of polluted sites in marine environments.
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Metais Pesados , Poluentes Químicos da Água , Bactérias/genética , China , Monitoramento Ambiental , Sedimentos Geológicos/química , Metais Pesados/análise , Medição de Risco , Poluentes Químicos da Água/análiseRESUMO
Acupuncture has been used for treating various medical conditions in traditional Chinese medicine. Both manual and electro-acupuncture stimulate specific acupoints to obtain local and systemic biological effects, but the underlying mechanisms remain unclear. Here, we used three-dimensional tissue-clearing technology to study acupoints on the Ren meridian of mice to reveal the distribution, density, branching, and relationships between blood vessels and nerves. Using topological Mapper methods, we found that sympathetic neurovascular networks were denser in the CV 4 acupoint compared with surrounding non-acupoints. Furthermore, high resolution in vivo real-time vascular imaging using the near infrared-II probe LZ-1105 demonstrated increased blood flow in the CV 4 acupoint compared with neighboring non-acupoints after manual or electro-acupuncture. Consistent with earlier findings, our research indicated that acupuncture could enhance local blood flow, and our high-resolution 3D images show for the first time the important role of sympathetic neurovascular networks in the CV 4 acupoint.
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Bread wheat expanded its habitat from a core area of the Fertile Crescent to global environments within ~10,000 years. The genetic mechanisms of this remarkable evolutionary success are not well understood. By whole-genome sequencing of populations from 25 subspecies within the genera Triticum and Aegilops, we identified composite introgression from wild populations contributing to a substantial portion (4-32%) of the bread wheat genome, which increased the genetic diversity of bread wheat and allowed its divergent adaptation. Meanwhile, convergent adaptation to human selection showed 2- to 16-fold enrichment relative to random expectation-a certain set of genes were repeatedly selected in Triticum species despite their drastic differences in ploidy levels and growing zones, indicating the important role of evolutionary constraints in shaping the adaptive landscape of bread wheat. These results showed the genetic necessities of wheat as a global crop and provided new perspectives on transferring adaptive success across species for crop improvement.
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Aclimatação/genética , Genoma de Planta/genética , Triticum/genética , Evolução Biológica , Pão/microbiologia , Produtos Agrícolas/genética , Produtos Agrícolas/fisiologia , Evolução Molecular , Variação Genética/genética , Filogenia , Sequenciamento Completo do GenomaRESUMO
It has been difficult to infer the genetic history of avocado breeding, owing to the role of hybridization in the origin of contemporary avocado cultivars. To address this difficulty, we used the model-based clustering program, STRUCTURE, and nucleotide polymorphism in 5960 bp of sequence from 4 nuclear loci to examine population structure in 21 wild avocado accessions. The origins of 33 cultivars were inferred relative to the wild sample. Nucleotide sequence diversity in domesticated avocados ranged between 80% and 90% of that observed for the same loci in wild avocado, depending on the diversity statistic used for comparison. Substantial genetic differentiation among 3 geographic groups of wild germplasm corresponded to the classically defined horticultural races of avocado. Previously undetected genetic differentiation was revealed in wild populations from Central Mexico, where 2 subpopulations were distinguished based on elevation and latitude.
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Variação Genética/genética , Persea/genética , Sequência de Bases , Fluxo Gênico , Genética Populacional , Genoma de Planta , Geografia , Haplótipos , México , Dados de Sequência Molecular , Polimorfismo GenéticoRESUMO
2,7-Dibromocarbazole (2,7-DBCZ) is one of the most frequently detected polyhalogenated carbazoles (PHCZs) in the environmental media. 2,7-DBCZ has attracted public attention for its potential for dioxin-like toxicity and cardiovascular toxicity. However, researches on the potential mechanism of angiogenesis inhibition by 2,7-DBCZ is still insufficient. Herein, human umbilical vein endothelial cells (HUVECs) were applied to explore the angiogenic effect of 2,7-DBCZ and the potential underlying mechanisms. 2,7-DBCZ significantly inhibited tube formation in HUVECs in the non-toxic concentration range. PCR array showed that 2,7-DBCZ reduced the expression proportion between VEGFs and Ang2, thereby inhibiting tube formation in HUVECs. Then, small RNA interference and DNA methylation assays were adopted to explore the potential mechanisms. It has been found that angiopoietin2 (Ang2)-silencing recovered the tube formation inhibited by 2,7-DBCZ. The DNA methylation status of Ang2 promoter also showed a demethylation tendency after exposure. In conclusion, 2,7-DBCZ could demethylate the Ang2 promoter to potentiate Ang2 expression, thus altering angiogenic phenotype of HUVECs by reducing the proportion between Ang2 and VEGFs. The data presented here can help to guide safety measures on the use of dioxin-like PHCZs for their potential adverse effects and provide a method for identifying the relevant biomarkers to assess their cardiovascular toxicity.
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Carbazóis/toxicidade , Metilação de DNA , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Regiões Promotoras Genéticas , Proteínas de Transporte Vesicular/genética , Células Cultivadas , HumanosRESUMO
Bisphenol analogues including bisphenol A (BPA), bisphenol AF (BPAF), bisphenol F (BPF), and bisphenol S (BPS) share similar chemical structures and endocrine disrupting effects. Their effects on metabolisms, however, are so far only marginally understood. In this study, NMR-based metabonomic profiles of HepG2 cell culture media and PCR array were used to assess the metabolomics disturbances and gene expression levels of HepG2 in response to four BPs (BPA, BPAF, BPF, and BPS). The results indicated that BP analogues resulted in disturbances in 7-15 metabolites that were classified as amino acid (alanine, glutamine, glutamate), intermediates and end-products in the glycolysis (pyruvate) and the tricarboxylic acid cycle (acetate, lactate). Their rank in order according to the number of metabolites and pathways was BPFâ¯>â¯BPAâ¯>â¯BPAFâ¯>â¯BPS. The common disrupted pathways (pyruvate metabolism; alanine, aspartate, and glutamate metabolism) indicated enhanced glycolysis. The following glucometabolic PCR array analysis suggested that although four BPs shared the capability of disrupting glucose metabolism, they may act through different mechanisms: BPAF has increased the pyruvate kinase (PKLR) expression level, which implied enhanced glycolysis that was agreed with NMR results. The other three BP analogues, however, decreased the expression level of glucokinase (GCK) that indicated glucose sensing impairment. Our results demonstrated the potential for using metabolomic and PCR array to understand the underlying action of mechanisms and identify the potential targets for future targeted risk assessment.
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Compostos Benzidrílicos/efeitos adversos , Disruptores Endócrinos/efeitos adversos , Poluentes Ambientais/efeitos adversos , Metaboloma/efeitos dos fármacos , Fenóis/efeitos adversos , Sulfonas/efeitos adversos , Transcriptoma/efeitos dos fármacos , Células Hep G2 , HumanosRESUMO
Resequencing studies provide the ultimate resolution of genetic diversity because they identify all mutations in a gene that are present within the sampled individuals. We report a resequencing study of Persea americana, a subtropical tree species native to Meso- and Central America and the progenitor of cultivated avocado. The sample includes 21 wild accessions from Mexico, Costa Rica, Ecuador, and the Dominican Republic. Estimated levels of nucleotide polymorphism and linkage disequilibrium (LD) are obtained from fully resolved haplotype data from 4 nuclear loci that span 5960 nucleotide sites. Results show that, although avocado is a subtropical tree crop and a predominantly outcrossing plant, the overall level of genetic variation is not exceptionally high (nucleotide diversity at silent sites, pi(sil) = 0.0102) compared with available estimates from temperate plant species. Intralocus LD decays rapidly to half the initial value within about 1 kb. Estimates of recombination rate (based on the sequence data) show that the rate is not exceptionally high when compared with annual plants such as wild barley or maize. Interlocus LD is significant owing to substantial population structure induced by mixing of the 3 botanical races of avocado.