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1.
New Phytol ; 241(2): 632-649, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37933224

RESUMEN

Although maturity date (MD) is an essential factor affecting fresh fruit marketing and has a pleiotropic effect on fruit taste qualities, the underlying mechanisms remain largely unclear. In this study, we functionally characterized two adjacent NAM-ATAF1/2-CUC2 (NAC) transcription factors (TFs), PpNAC1 and PpNAC5, both of which were associated with fruit MD in peach. PpNAC1 and PpNAC5 were found capable of activating transcription of genes associated with cell elongation, cell wall degradation and ethylene biosynthesis, suggesting their regulatory roles in fruit enlargement and ripening. Furthermore, PpNAC1 and PpNAC5 had pleiotropic effects on fruit taste due to their ability to activate transcription of genes for sugar accumulation and organic acid degradation. Interestingly, both PpNAC1 and PpNAC5 orthologues were found in fruit-producing angiosperms and adjacently arranged in all 91 tested dicots but absent in fruitless gymnosperms, suggesting their important roles in fruit development. Our results provide insight into the regulatory roles of NAC TFs in MD and fruit taste.


Asunto(s)
Prunus persica , Factores de Transcripción , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Prunus persica/genética , Frutas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas
2.
BMC Cancer ; 24(1): 860, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39026185

RESUMEN

BACKGROUND AND PURPOSE: Sarcopenia has been demonstrated to be adversely correlated with the prognosis of various cancers. Our study aimed to estimate the prognostic value of sarcopenia in conjunction with inflammatory indices [neutrophil-to-lymphocyte ratio (NLR)] for evaluating the prognosis of patients with esophageal squamous cell carcinoma (ESCC) undergoing chemoradiotherapy. MATERIALS AND METHODS: This study retrospectively analyzed 255 patients with ESCC who received chemoradiotherapy from January 2012 to December 2018. Multivariate Cox regression analysis was employed to identify prognostic values of assessed factors following a novel prognostic scoring system (SMI-NLR), covering sarcopenia and NLR during different treatment courses. RESULTS: Kaplan-Meier analysis revealed significantly greater overall survival (OS) rates in the nonsarcopenia group than in the sarcopenia group (P = 0.011). The low NLR group (< 4.84) demonstrated significantly higher OS rates than the high NLR group (≥ 4.84) (P < 0.001). The SMI-NLR prognostic model was established through multivariate analysis, revealing that Karnofsky performance status [hazard ratio (HR) = 0.285; 95% confidence interval (CI) = 0.117-0.699; P = 0.006], clinical staging (HR = 5.223; 95% CI = 1.879-14.514; P = 0.002), and preSMI-NLR (HR = 0.544; 95% CI = 0.330-0.898; P = 0.017) were independent factors affecting the prognosis of patients with ESCC. Nomograms were constructed based on these data providing more accurate 1-, 3-, and 5-year survival rates for patients with ESCC. CONCLUSION: Our study indicates the effectiveness of the combined sarcopenia and NLR prognostic model for the prognostic evaluation of patients with ESCC having undergone chemoradiotherapy.


Asunto(s)
Quimioradioterapia , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Neutrófilos , Sarcopenia , Humanos , Femenino , Sarcopenia/etiología , Masculino , Quimioradioterapia/métodos , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Pronóstico , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Anciano , Linfocitos , Estimación de Kaplan-Meier , Inflamación , Adulto , Tasa de Supervivencia , Recuento de Linfocitos
3.
J Insect Sci ; 24(1)2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38412292

RESUMEN

In this study, a vitellogenin like1 gene (SfVg-like1) in Sogatella furcifera was identified. The open reading frame (ORF) encoded 1,321 amino acid sequence. Structure analysis reveals that the amino acid sequence of SfVg-like1 has 3 conserved LPD_N, DUF1943 and VWFD domains. Phylogenetic analyses showed that SfVg-like1 was clustered in the same branch with the Vg-like1 of Nilaparvata lugens (100% bootstrap value) compared with other Hemiptera insects Vgs associated with vitellogenesis. Temporo-spatial expression analyses showed that SfVg-like1 expressed during all stages, and in both genders. The relative expression levels of SfVg-like1 mRNA were higher in adults than in nymph developmental stages. The knockdown of SfVg-like1 gene resulted in the inhibition of the ovarian development in female adults, whereas the morphology of the testis in male adults was not been affected. The silence of SfVg-like1 could decrease the relative expression levels of target of rapamycin (SfTOR, GenBank MW193765) and vitellogenin (SfVg, GenBank MH271114) genes significantly in female adults. However, the knockdown of SfTOR or SfVg genes in female adults did not affect the transcript level of SfVg-like1. Therefore, it demonstrated that SfVg-like1 might locate on the upstream signaling pathways of SfTOR and SfVg. These results demonstrate that SfVg-like1 is essential for S. furcifera reproduction, and it could be the potential target for the control of this pest.


Asunto(s)
Hemípteros , Vitelogeninas , Femenino , Masculino , Animales , Vitelogeninas/genética , Vitelogeninas/metabolismo , Filogenia , Secuencia de Aminoácidos , Reproducción
4.
J Integr Plant Biol ; 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39185667

RESUMEN

WRKY transcription factors play key roles in plant resistance to various stresses, but their roles in fruit ripening remain largely unknown. Here, we report a WRKY gene PpWRKY14 involved in the regulation of fruit ripening in peach. The expression of PpWRKY14 showed an increasing trend throughout fruit development. PpWRKY14 was a target gene of PpNAC1, a master regulator of peach fruit ripening. PpWRKY14 could directly bind to the promoters of PpACS1 and PpACO1 to induce their expression, and this induction was greatly enhanced when PpWRKY14 formed a dimer with PpNAC1. However, the transcription of PpNAC1 could be directly suppressed by two EIN3/EIL1 genes, PpEIL2 and PpEIL3. The PpEIL2/3 genes were highly expressed at the early stages of fruit development, but their expression was programmed to decrease significantly during the ripening stage, thus derepressing the expression of PpNAC1. These results suggested a PpEIL2/3-PpNAC1-PpWRKY14 module that regulates fruit ripening by modulating ethylene production in peach. Our results provided an insight into the regulatory roles of EIN3/EIL1 and WRKY genes in fruit ripening.

5.
Int J Mol Sci ; 23(15)2022 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-35897828

RESUMEN

The white-backed planthopper (WBPH), Sogatella furcifera, is one of the most important piercing-sucking pests of rice (Oryza sativa) in Asia. Mucin-like salivary protein (SFMLP) is highly expressed in the salivary glands of WBPH, which plays an important role in WBPH feeding. In this study, WBPH injected with dsSFMLP had difficulty in sucking phloem sap from rice plants, which significantly reduced their food intake, weight, and survival. In contrast, the knockdown of the SFMLP gene had only a marginal effect on the survival of WBPH fed an artificial diet. Further studies showed that silencing SFMLP resulted in the short and single-branched salivary sheaths secretion and less formation of salivary flanges in rice. These data suggest that SFMLP is involved in the formation of the salivary sheath and is essential for feeding in WBPH. Overexpression of the SFMLP gene in rice plants promoted the feeding of WBPH, whereas silencing the gene in rice plants significantly decreased WBPH performance. Additionally, it was found that overexpression of SFMLP in rice plants elicited the signalling pathway of SA (salicylic acid) while suppressing JA (jasmonic acid); in contrast, silencing of the SFMLP gene in rice plants showed the opposite results. This study clarified the function of SFMLP in WBPH feeding as well as mediating rice defences.


Asunto(s)
Hemípteros , Oryza , Animales , Hemípteros/genética , Mucinas , Oryza/genética , Saliva , Glándulas Salivales
6.
Plant Mol Biol ; 105(3): 321-332, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33128723

RESUMEN

KEY MESSAGE: A candidate gene, designate PpRPH, in the D locus was identified to control fruit acidity in peach. Fruit acidity has a strong impact on organoleptic quality of fruit. Peach fruit acidity is controlled by a large-effect D locus on chromosome 5. In this study, the D locus was mapped to a 509-kb interval, with two markers, 5dC720 and 5C1019, co-segregating with the non-acid/acid trait of peach fruit. Within this interval, a candidate gene encoding a putative small protein, designated PpRPH, showed a consistency between gene expression and fruit acidity, with up- and down-regulation in non-acidic and acidic fruits, respectively. Transient ectopic expression of PpRPH in tobacco leaves caused an increase of pH by approximately 40% compared to the control transformed with empty vector. Whereas, the concentrations of citrate and malate decreased significantly by 22% and 37%, respectively, with respect to the empty vector control. All these results suggest that PpRPH is a strong candidate gene of the D locus. These findings contribute to our overall understanding of the complex mechanism underlying fruit acidity in peach as well as that in other fruit crops.


Asunto(s)
Genes de Plantas , Estudios de Asociación Genética , Sitios Genéticos , Prunus persica/genética , Secuencia de Bases , Mapeo Cromosómico , Segregación Cromosómica/genética , Frutas/genética , Regulación de la Expresión Génica de las Plantas , Marcadores Genéticos , Genotipo , Concentración de Iones de Hidrógeno , Polimorfismo Genético , Carácter Cuantitativo Heredable , Reproducibilidad de los Resultados , Transcriptoma/genética
7.
Opt Lett ; 46(7): 1676-1679, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33793516

RESUMEN

In this Letter, we report a dual division of focal plane (DoFP) polarimeters-based full Mueller matrix microscope (DoFPs-MMM) for fast polarization imaging. Both acquisition speed and measurement accuracy are improved compared with those of a Mueller matrix microscope based on dual rotating retarders. Then, the system is applied to probe the polarization properties of a red blood cells smear. The experimental results show that a DoFPs-MMM has the potential to be a powerful tool for probing dynamic processes in living cells in future studies.


Asunto(s)
Microscopía/instrumentación , Algoritmos , Diseño de Equipo , Microscopía de Polarización
8.
Future Oncol ; 17(20): 2647-2657, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34008415

RESUMEN

Aim: To explore the clinical utility of the systemic immune-inflammation index (SII) for predicting the prognosis of esophageal squamous cell carcinoma (ESCC). Patients & methods: After calculating the SII in 180 patients with ESCC, the relationship between SII values and the pre-/post-radiotherapy SII ratio and overall survival was determined. Results: The median overall survival was 649 days for the entire group and 909 and 466 days for the high and low pre-/post-radiotherapy SII ratio groups, respectively. Multivariate analysis identified Karnofsky performance status (p = 0.045), lymphatic metastasis (p = 0.032), mid-radiotherapy SII (p < 0.001) and pre-/post-radiotherapy SII ratio (p = 0.003) as independent prognostic factors. Conclusion: The pre-/post-radiotherapy SII ratio and mid-radiotherapy SII are potentially effective markers for predicting ESCC prognosis.


Lay abstract The systemic immune-inflammation index (SII) is calculated from the counts of peripheral blood platelets (P), neutrophils (N) and lymphocytes (L) per liter according to the formula SII = P × N/L. The SII is associated with poor survival in certain cancer types. However, some reports have examined the prognostic value of the SII in patients with esophageal squamous cell carcinoma (ESCC) who were undergoing radiotherapy or radical chemoradiotherapy. As such, the current study sought to investigate the clinical prognostic value of the SII during radiotherapy and the ratio of the SII before and after radiotherapy in patients with ESCC who were undergoing chemoradiotherapy or radiotherapy. The study found that the pre-/post-radiotherapy SII ratio and mid-radiotherapy SII are potentially effective markers for predicting ESCC prognosis.


Asunto(s)
Plaquetas/inmunología , Quimioradioterapia/estadística & datos numéricos , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago/mortalidad , Linfocitos/inmunología , Neutrófilos/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Quimioradioterapia/métodos , Toma de Decisiones Clínicas , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/sangre , Carcinoma de Células Escamosas de Esófago/inmunología , Carcinoma de Células Escamosas de Esófago/terapia , Estudios de Factibilidad , Femenino , Humanos , Inflamación/sangre , Inflamación/diagnóstico , Estimación de Kaplan-Meier , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Selección de Paciente , Recuento de Plaquetas , Pronóstico , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Análisis de Supervivencia , Resultado del Tratamiento
9.
Appl Opt ; 60(5): 1380-1386, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33690582

RESUMEN

Mueller matrix (MM) imaging has demonstrated its potential application in much research, especially in probing delicate and complex biomedical specimens. Qualities of MM images are important for further quantitative characterization. In this paper, we compare the performance and imaging qualities of three calibration methods. Air, waveplate and cell specimen are selected as standard samples for comparison. In addition, we also propose two general MM imaging quality indices that can be used as quantitative evaluations for MM imaging systems and calculation processes based on real samples. The numerical calibration method turns out to give the best accuracy and precision, as well as the best image qualities.


Asunto(s)
Microscopía de Polarización/métodos , Imagen Óptica/métodos , Aire , Calibración/normas , Células HeLa , Humanos , Luz , Microscopía de Polarización/normas , Imagen Óptica/normas
10.
Int J Mol Sci ; 23(1)2021 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-35008668

RESUMEN

Though numerous studies have focused on the cell wall disassembly of bananas during the ripening process, the modification of homogalacturonan (HG) during fruit development remains exclusive. To better understand the role of HGs in controlling banana fruit growth and ripening, RNA-Seq, qPCR, immunofluorescence labeling, and biochemical methods were employed to reveal their dynamic changes in banana peels during these processes. Most HG-modifying genes in banana peels showed a decline in expression during fruit development. Four polygalacturonase and three pectin acetylesterases showing higher expression levels at later developmental stages than earlier ones might be related to fruit expansion. Six out of the 10 top genes in the Core Enrichment Gene Set were HG degradation genes, and all were upregulated after softening, paralleled to the significant increase in HG degradation enzyme activities, decline in peel firmness, and the epitope levels of 2F4, CCRC-M38, JIM7, and LM18 antibodies. Most differentially expressed alpha-1,4-galacturonosyltransferases were upregulated by ethylene treatment, suggesting active HG biosynthesis during the fruit softening process. The epitope level of the CCRC-M38 antibody was positively correlated to the firmness of banana peel during fruit development and ripening. These results have provided new insights into the role of cell wall HGs in fruit development and ripening.


Asunto(s)
Frutas/crecimiento & desarrollo , Frutas/metabolismo , Musa/crecimiento & desarrollo , Musa/metabolismo , Pectinas/metabolismo , Anticuerpos/metabolismo , Epítopos/metabolismo , Frutas/anatomía & histología , Frutas/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Musa/anatomía & histología , Musa/genética , Factores de Tiempo
11.
J Econ Entomol ; 109(2): 879-86, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26612891

RESUMEN

The white-backed planthopper, Sogatella furcifera (Hemiptera, Delphacidae), is one of the most devastating rice pests. For a better control strategy, various genetic studies have been conducted using reverse-transcription quantitative real-time polymerase chain reaction (qRT-PCR). The appropriate application of qRT-PCR requires reliable endogenous controls; however, studies on this aspect of the white-backed planthopper are lacking. In the present study, nine commonly used reference genes, elongation factor 1-α (EF1-α), polyubiquitin (UB), ribosomal protein S18 (RPS18), actin 1 (ACT), α-1 tubulin (TUB), glyceraldehyde-3-phosphate (GAPDH), ribosomal protein L9 (RPL9), ribosomal protein L10 (RPL10), and 18S ribosomal RNA (18S), were evaluated by qRT-PCR for their expression stability under four different experimental conditions (different developmental stages, acquisition of Southern rice black-streaked dwarf virus (SRBSDV), different tissues, and different temperature stress). These results were analyzed using four software programs (geNorm, NormFinder, BestKeeper, and the delta Ct method) and a Web-based comprehensive tool RefFinder to compare and rank candidate reference genes. According to the results of RefFinder analysis, which integrates the abovementioned four software programs, TUB was ranked as the most suitable reference gene at different developmental stages and under different temperature stress, and GAPDH and RPL9 showed the highest stability for acquisition of SRBSDV and different tissues, respectively. These results will provide a solid foundation for future gene expression study on the white-backed planthopper, and also will give aids in establishing a standardized qRT-PCR procedure for other related insects.


Asunto(s)
Expresión Génica , Genes de Insecto , Hemípteros/genética , Animales , Reacción en Cadena en Tiempo Real de la Polimerasa , Estándares de Referencia
12.
J Econ Entomol ; 108(3): 917-24, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26470211

RESUMEN

The white-backed planthopper, Sogatella furcifera (Horvath), is currently the only confirmed vector of Southern rice black-streaked dwarf virus (SRBSDV), which causes severe rice production losses in China. In this study, an absolute quantification qPCR method was used to detect viral gene mRNA expression levels at different developmental stages of white-backed planthoppers fed SRBSDV-infected rice plants. A comparison of viral copy numbers of the SRBSDV S10 gene at the same developmental stage indicated that the white-backed planthopper had higher viral copy numbers when the virus was acquired at the earlier developmental stages. The adult-stage white-backed planthoppers that had acquired the virus at the first-second nymphal stage displayed significantly higher viral titers than white-backed planthoppers that acquired the virus at the third-fourth nymphal stage, at the fifth nymphal stage, and at the adult stage. The fifth nymphal stage white-backed planthoppers that acquired the virus at the first-second nymphal stage displayed higher viral copy numbers than fifth nymphal stage white-backed planthoppers that acquired the virus at the third-fourth nymphal stage and at the fifth nymphal stage. The highest viral load value appeared in the middle adult stage. The annual immigration characteristics of white-backed planthoppers would be beneficial for the dispersal of SRBSDV because this virus could be transmitted far away following the migration of vigorous planthoppers. Therefore, investigating the change in the viral load at different life stages of SRBSDV-positive individuals is required to develop more effective control of the spread of SRBSDV in the field.


Asunto(s)
Hemípteros/virología , Insectos Vectores/virología , Oryza/virología , Enfermedades de las Plantas/virología , Reoviridae/fisiología , Animales , China , Hemípteros/crecimiento & desarrollo , Ninfa/crecimiento & desarrollo , Ninfa/virología , Reacción en Cadena en Tiempo Real de la Polimerasa , Reoviridae/genética , Carga Viral
13.
J Econ Entomol ; 108(1): 69-76, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26470105

RESUMEN

Planthopper-targeting insecticides, pymetrozine, thiamethoxam, buprofezin, and nitenpyram, were tested under laboratory conditions for toxicity to adults and immatures of Trichogramma chilonis Ishii, using standard tests described by International Organization for Biological Control (IOBC). In the dry film residue test, all insecticides resulted in >90% mortality in T. chilonis adults and were ranked as moderately harmful. Persistent toxicity tests revealed that nitenpyram was short-lived and the other three insecticides were of slightly persistent toxicity to the wasp adults. Effects of the insecticides on egg, larval, and prepupal stages of T. chilonis were investigated with striped stem borer as host. At the three stages of T. chilonis (within the host egg), all the insecticides reduced parasitism rate, but nitenpyram and pymetrozine applied at egg stage, buprofezin and nitenpyram at larval stage, and buprofezin and thiamethoxam at prepupal stage of T. chilonis reduced parasitism by <30% in comparison with the control, and were thus ranked as harmless. Although insecticide treatment of the three immature stages of T. chilonis all reduced wasp emergence from host eggs, only thiamethoxam applied at larval stage and buprofezin at prepupal stage resulted in >30% reduction in emergence rate as compared with the control and were categorized as harmful. Immature duration of T. chilonis was only significantly extended by nitenpyram applied to egg stage than the control. Sex ratio of emerged wasps was not affected by the treatment to immature stages. The data are of significance for IPM programs incorporating inundative release of T. chilonis for control of lepidopteran rice pests where there is heavy co-occurrence of planthoppers.


Asunto(s)
Insecticidas , Control Biológico de Vectores , Avispas , Animales , Femenino , Larva , Masculino , Óvulo , Pruebas de Toxicidad Aguda
14.
J Econ Entomol ; 107(3): 955-63, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25026653

RESUMEN

Trichogramma species and strains differ significantly in host specificity and performance. Nine Trichogramma strains, six of them collected from paddy fields in the Greater Mekong Subregion, were evaluated for performance on eggs of the striped stem borer, Chilo suppressalis (Walker), in both laboratory and field tests to determine potential Trichogramma strains that can be used in an inundative release in an integrated pest management program. In the laboratory glass vial tests, all strains showed higher parasitism rates on 0-24-h eggs than on the two older age groups (24-48 and 48-72 h). Wasp emergence rate was also higher from parasitized 0-24-h striped stem borer eggs, while Trichogramma immature duration was significantly prolonged on 0-24-h striped stem borer eggs. Parasitism rates differed among Trichogramma strains, with Trichogramma chilonis Ishii CJ strain showing significantly higher parasitism rate than any other strains. In the field tests, parasitism of sentinel striped stem borer eggs by Trichogramma strains released at 50,000, 100,000, and 200,000 wasps per hectare was low, with marginal yet significant differences between strains. The highest parasitism was achieved by T. chilonis CJ strain at the high and medium release rates. Hence, it can be concluded that T. chilonis CJ strain released at 100,000 wasps per hectare may be a cost-effective control tactic for field releases targeting striped stem borer.


Asunto(s)
Mariposas Nocturnas/parasitología , Control Biológico de Vectores/métodos , Avispas/fisiología , Animales , China , Productos Agrícolas/crecimiento & desarrollo , Femenino , Larva/crecimiento & desarrollo , Larva/parasitología , Larva/fisiología , Mariposas Nocturnas/crecimiento & desarrollo , Oryza/crecimiento & desarrollo , Óvulo/crecimiento & desarrollo , Óvulo/parasitología , Especificidad de la Especie , Avispas/crecimiento & desarrollo
15.
Expert Opin Drug Saf ; : 1-9, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39021273

RESUMEN

BACKGROUND: This study aims to analyze the adverse event reports (AERs) to vericiguat using data from the Food and Drug Administration Adverse Event Reporting System (FAERS) and provide evidence for the clinical use. METHODS: AERs due to vericiguat from 2021Q1 to 2024Q1 identified as the primary suspect were screened, with duplicate reports subsequently eliminated. Various quantitative signal detection methods, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and multi-item gamma poisson shrinker, were then employed for data mining and analysis. Signal strength is represented by the 95% confidence interval, information component (IC), and empirical Bayesian geometric mean (EBGM). RESULTS: A total of 617 vericiguat-related AERs were identified. Strong signals were observed in 21 system organ classes. Furthermore, the most frequently reported preferred terms (PT) was hypotension (n = 86, ROR 25.92, PRR 24.11, IC 4.59, EBGM 24.07), followed by dizziness (n = 52, ROR 6.44, PRR 6.20, IC 2.63, EBGM 6.20), malaise (n = 25, ROR 3.59, PRR 3.54, IC 1.82, EBGM 3.54), blood pressure decreased (n = 23, ROR 20.00, PRR 19.64, IC 4.29, EBGM 19.61), and anemia (n = 21, ROR 6.67, PRR 6.57, IC 2.72, EBGM 6.57). CONCLUSIONS: This study extended the adverse reactions documented in the FDA instruction and provided supplementary evidence regarding the clinical safety of vericiguat.

16.
Gene ; 927: 148760, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38992762

RESUMEN

The CRISPR-Cas system is a powerful gene editing technology, the clinical application of which is currently constrained due to safety concerns. A substantial body of safety research concerning Cas9 exists; however, scant attention has been directed toward investigating the safety profile of the emergent Cas13 system, which confers RNA editing capabilities. In particular, uncertainties persist regarding the potential cellular impacts of Cas13d in the absence of reliance on a cleavage effect. In this study, we conducted an initial exploration of the effects of Cas13d on HeLa cells. Total RNA and protein samples were extracted after transfection with a Cas13d-expressing plasmid construct, followed by transcriptomic and proteomic sequencing. Differential gene expression analysis identified 94 upregulated and 847 downregulated genes, while differential protein expression analysis identified 185 upregulated and 231 downregulated proteins. Subsequently, enrichment analysis was conducted on the transcriptome and proteome sequencing data, revealing that the PI3K-Akt signaling pathway is a common term. After intersecting the differentially expressed genes enriched in the PI3K-Akt signaling pathway with all the differentially expressed proteins, it was found that the expression of the related regulatory gene PFKFB4 was upregulated. Moreover, western blot analysis demonstrated that Cas13d can mediate PI3K-Akt signaling upregulation through overexpression of PFKFB4. CCK-8 assay, colony formation, and EdU experiments showed that Cas13d can promote cell proliferation. Our data demonstrate, for the first time, that Cas13d significantly impacts the transcriptomic and proteomic profiles, and proliferation phenotype, of HeLa cells, thus offering novel insights into safety considerations regarding gene editing systems.


Asunto(s)
Sistemas CRISPR-Cas , Proliferación Celular , Fosfatidilinositol 3-Quinasas , Fosfofructoquinasa-2 , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Regulación hacia Arriba , Humanos , Células HeLa , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfofructoquinasa-2/genética , Fosfofructoquinasa-2/metabolismo , Proteómica/métodos , Edición Génica/métodos , Transcriptoma , Multiómica
17.
Diabetes Res Clin Pract ; 213: 111725, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38823455

RESUMEN

BACKGROUND: Clinical studies have shown that cardiovascular diseases in patients with type 1 diabetes (T1D) are often atypical or asymptomatic. The link between T1D and arrhythmia remains unclear. To infer causality between T1D and arrhythmia at the genetic level, we conducted a Mendelian randomization study through the genetic tools of T1D. METHODS: In this study, we used genetic variables and summary statistics from genome-wide association studies of T1D and arrhythmia. Single nucleotide polymorphisms were selected based on the assumptions of instrumental variables. The inverse variance-weighted method was used as the primary analysis to summarize the causal effects between exposure and outcome. The weighted median and weighted mode methods were used as secondary methods. We tested for horizontal pleiotropy using the MR-Egger method and detected heterogeneity using the Q-test. A leave-one-out sensitivity analysis was performed. Scatter plots, forest plots, and funnel plots were used to visualize the results of the MR analysis. RESULTS: In this study, we selected 28 T1D-related SNPs as instrumental variables. The IVW [odds ratio (OR) = 0.98, 95 % confidence interval (CI) = 0.97-1.00, P = 0.008], weighted median (OR = 0.98, 95 % CI = 0.96 - 0.99, P = 0.009), and weighted mode (OR = 0.98, 95 % CI = 0.96-0.99, P = 0.018) analysis methods suggested a causal effect of T1D on arrhythmia. The MR-Egger method indicated no horizontal pleiotropy (P = 0.649), and the Q-test showed no heterogeneity (IVW, P = 0.653). CONCLUSIONS: Our MR analysis revealed a causal association between T1D and the development of arrhythmia, indicating that patients with T1D had a higher risk of arrhythmia.


Asunto(s)
Arritmias Cardíacas , Diabetes Mellitus Tipo 1 , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/epidemiología , Arritmias Cardíacas/genética , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/etiología , Predisposición Genética a la Enfermedad
18.
Food Chem X ; 23: 101698, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39211764

RESUMEN

Peach fruit is an important natural source of phenolic compounds that are well-known to have health benefits, but their metabolic basis remain elusive. Here, we report on phenolic compounds accumulation and antioxidant activity of ripe fruits in peach. A considerable variation in phenolic compounds content was observed among peach germplasm, with significantly higher levels detected in red-fleshed peaches compared to non-red-fleshed peaches. Antioxidant activity of crude extracts from ripe fruits showed significant differences among peach germplasm, with red-fleshed peaches having the strongest antioxidant activity. Intriguingly, it was observed that total phenolics instead of anthocyanins were strongly associated with antioxidant activity. Phenolic compounds content and antioxidant activity showed dynamic changes throughout fruit development, and these were much higher in the peel than in the flesh. Metabolomic analysis unveiled a coordinated accumulation of anthocyanins as well as key components of flavonoids and phenolic acids, which endows red-fleshed peaches with superior antioxidant activity.

19.
Cell Prolif ; 56(3): e13367, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36547008

RESUMEN

Protein translation is a critical regulatory event involved in nearly all physiological and pathological processes. Eukaryotic translation initiation factors are dedicated to translation initiation, the most highly regulated stage of protein synthesis. Eukaryotic translation initiation factor 4G2 (eIF4G2, also called p97, NAT1 and DAP5), an eIF4G family member that lacks the binding sites for 5' cap binding protein eIF4E, is widely considered to be a key factor for internal ribosome entry sites (IRESs)-mediated cap-independent translation. However, recent findings demonstrate that eIF4G2 also supports many other translation initiation pathways. In this review, we summarize the role of eIF4G2 in a variety of cap-independent and -dependent translation initiation events. Additionally, we also update recent findings regarding the role of eIF4G2 in apoptosis, cell survival, cell differentiation and embryonic development. These studies reveal an emerging new picture of how eIF4G2 utilizes diverse translational mechanisms to regulate gene expression.


Asunto(s)
Factor 4G Eucariótico de Iniciación , Biosíntesis de Proteínas , Apoptosis , Diferenciación Celular , Factor 4E Eucariótico de Iniciación/genética , Factor 4E Eucariótico de Iniciación/metabolismo , Factor 4G Eucariótico de Iniciación/genética , Factor 4G Eucariótico de Iniciación/metabolismo , Procesamiento Proteico-Postraduccional , Humanos
20.
Hortic Res ; 10(9): uhad158, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37719277

RESUMEN

Although auxin is known to induce ethylene biosynthesis in some Rosaceae fruit crops, the mechanisms underlying the auxin-ethylene interaction during fruit ripening remain largely unknown. Here, the regulatory role of an auxin response factor, PpARF6, in fruit ripening was investigated in peach. Peach fruits showed accelerated ripening after treatment with auxin and PpARF6 was found to be significantly induced. PpARF6 not only could induce ethylene synthesis by directly activating the transcription of ethylene biosynthetic genes, but also competed with EIN3-binding F-box proteins PpEBF1/2 for binding to ethylene-insensitive3-like proteins PpEIL2/3, thereby keeping PpEIL2/3 active. Moreover, PpARF6 showed an interaction with PpEIL2/3 to enhance the PpEIL2/3-activated transcription of ethylene biosynthetic genes. Additionally, ectopic overexpression of PpARF6 in tomato accelerated fruit ripening by promoting the expression of genes involved in ethylene synthesis and fruit texture. In summary, our results revealed a positive regulatory role of PpARF6 in peach fruit ripening via integrating auxin and ethylene signaling.

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