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1.
Ther Adv Med Oncol ; 16: 17588359241271845, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246808

RESUMO

Background: Genetic studies of ovarian cancer (OC) have historically focused on BRCA1/2 mutations, lacking other studies of homologous recombination repair (HRR). Poly (ADP-ribose) polymerase inhibitors (PARPi) exploit synthetic lethality to significantly improve OC treatment outcomes, especially in BRCA1/2 deficiency patients. Objectives: Our study aims to construct a mutation map of HRR genes in OC and identify factors influencing the efficacy of PARPi. Design: A retrospective observational analysis of HRR gene variation data from 695 OC patients from March 2019 to February 2022 was performed. Methods: The HRR gene variation data of 695 OC patients who underwent next-generation sequencing (NGS) in the First Affiliated Hospital of Zhengzhou University were retrospectively collected. Clinical data on the use of PARPi in these patients were also gathered to identify factors that may interfere with the efficacy of PARPi. Results: Out of 127 pathogenic variants in the BRCA1/2 genes, 104 (81.9%) were BRCA1 mutations, and 23 (18.1%) were BRCA2 mutations. Among the 59 variants of uncertain significance (VUS), 20 (33.9%) were BRCA1, while 39 (66.1%) were BRCA2 mutations. In addition to BRCA1/2, HRR gene results showed that 9 (69%) of 13 were HRR pathway pathogenic variants; and 16 (1.7%) of 116 VUS were Food and Drug Administration (FDA)-approved mutated HRR genes. Notably, the treatment regimen significantly influenced the effectiveness of PARPi, especially when using first-line maintenance therapy, leading to enhanced progression-free survival (PFS) compared to alternative protocols. Conclusion: Focusing on HRR gene mutations and supporting clinical research about PARPi in OC patients is crucial for developing precision treatment strategies and enhancing prognosis.

2.
Transl Oncol ; 50: 102130, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39303357

RESUMO

Ovarian cancer is a highly heterogeneous tumor with a poor prognosis. The lack of reliable and efficient research models that can accurately mimic heterogeneity has impeded in-depth investigations and hindered the clinical translation of research findings in ovarian cancer. Organoid models have emerged as a promising in vitro approach, demonstrating remarkable fidelity to the histological, molecular, genomic, and transcriptomic features of their tissues of origin. In recent years, organoids have contributed to advancing our understanding of ovarian cancer initiation, metastasis, and drug resistance mechanisms, as well as facilitating clinical screening of effective therapeutic agents. The establishment of high-throughput organoid culture systems, coupled with cutting-edge technologies such as organ-on-a-chip, genetic engineering, and 3D printing, has tremendous potential for accelerating ovarian cancer research translation. In this review, we present a comprehensive overview of the latest exploration of organoids in basic ovarian cancer research and clinical translation. Furthermore, we discuss the prospects and challenges associated with the use of organoids and related novel technologies in the context of ovarian cancer. This review provides insights into the application of organoids in ovarian cancer.

3.
Int J Mol Sci ; 25(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38891905

RESUMO

The DABB proteins, which are characterized by stress-responsive dimeric A/B barrel domains, have multiple functions in plant biology. In Arabidopsis thaliana, these proteins play a crucial role in defending against various pathogenic fungi. However, the specific roles of DABB proteins in Brassica napus remain elusive. In this study, 16 DABB encoding genes were identified, distributed across 10 chromosomes of the B. napus genome, which were classified into 5 branches based on phylogenetic analysis. Genes within the same branch exhibited similar structural domains, conserved motifs, and three-dimensional structures, indicative of the conservation of BnaDABB genes (BnaDABBs). Furthermore, the enrichment of numerous cis-acting elements in hormone induction and light response were revealed in the promoters of BnaDABBs. Expression pattern analysis demonstrated the involvement of BnaDABBs, not only in the organ development of B. napus but also in response to abiotic stresses and Sclerotinia sclerotiorum infection. Altogether, these findings imply the significant impacts of BnaDABBs on plant growth and development, as well as stress responses.


Assuntos
Brassica napus , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas , Estresse Fisiológico , Brassica napus/genética , Brassica napus/microbiologia , Brassica napus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Genoma de Planta , Ascomicetos/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/genética
4.
Int J Mol Sci ; 24(16)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37628959

RESUMO

Chalkiness is a key determinant that directly affects the appearance and cooking quality of rice grains. Previously, Floury endosperm 2 (FLO2) was reported to be involved in the formation of rice chalkiness; however, its regulation mechanism is still unclear. Here, FLO2 interaction factor 3 (OsFIF3), a bHLH transcription factor, was identified and analyzed in Oryza sativa. A significant increase in chalkiness was observed in OsFIF3-overexpressed grains, coupled with a round, hollow filling of starch granules and reduced grain weight. OsFIF3 is evolutionarily conserved in monocotyledons, but variable in dicotyledons. Subcellular localization revealed the predominant localization of OsFIF3 in the nucleus. The DAP-seq (DNA affinity purification sequencing) results showed that OsFIF3 could affect the transcriptional accumulation of ß-amylase 1, α-amylase isozyme 2A-like, pectinesterase 11, ß-glucosidase 28 like, pectinesterase, sucrose transport protein 1 (SUT1), and FLO2 through the binding of the CACGTG motif on their promoters. Moreover, FLO2 and SUT1 with abundant OsFIF3 binding signals showed significant expression reduction in OsFIF3 overexpression lines, further confirming OsFIF3's role in starch metabolism regulation and energy material allocation. Taken together, these findings show that the overexpression of OsFIF3 inhibits the expression of FLO2 and SUT1, thereby increasing grain chalkiness and affecting grain weight.


Assuntos
Oryza , Oryza/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Metabolismo dos Carboidratos , Grão Comestível , Sementes , Carbonato de Cálcio
5.
Front Nutr ; 10: 1126456, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37006930

RESUMO

Mussels are a kind of economically valuable ocean bivalve shellfish. It has a short harvest period and is susceptible to contamination during storage and processing. Having proper preservation methods is critical to prevent quality deterioration. However, the effect of low voltage variable frequency electric field and compound preservative on the freshness of steamed mussels in ice-temperature storage are still unknown. We utilized the method of coefficient variation weighting to calculate the overall scores of steamed mussels stored under different preservation conditions. The protein physicochemical properties of samples, the growth curves of two dominant spoilage bacteria; Bacillus subtilis and Pseudomonas in the mussels as well as the Structural changes of the cell membranes were mensurated. The results show that compared with the preservative group and the low voltage variable frequency electric field group, the compound preservatives combined with the electric field group had the highest overall score and thus the best preservation effect. Compared with the blank group, the total sulfhydryl content and myogenic fibrin content of the combined group decreased at the slowest rate, 19.46%, and 44.92%, respectively. The hydrophobicity of the protein surface increased by only 5.67%, with the best water retention, indicating that the samples of the combined group had the least protein deterioration in the combined group. The inhibition mechanism of the combined group inhibited the growth of two dominant spoilage bacteria: Bacillus subtilis and Pseudomonas, in the mussels, destroying the integrity of the cell membrane structure and changing the cell morphology. Overall, we found that the combination of the composite preservatives and the low voltage variable frequency electric field can maintain the best quality of steamed mussels during ice-temperature storage and slow down the rate of protein deterioration during storage. This study proposed a new method of mussel preservation, which provides a new idea for the application of low voltage variable frequency electric field and compound preservative in the preservation of aquatic products.

6.
J Fungi (Basel) ; 10(1)2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38248922

RESUMO

The ADP-ribosylation factor 6 (Arf6), as the only member of the Arf family III protein, has been extensively studied for its diverse biological functions in animals. Previously, the Arf6 protein in Magnaporthe oryzae was found to be crucial for endocytosis and polarity establishment during asexual development. However, its role remains unclear in S. sclerotiorum. Here, we identified and characterized SsArf6 in S. sclerotiorum using a reverse genetic approach. Deletion of SsArf6 impaired hyphal growth and development and produced more branches. Interestingly, knockout of SsArf6 resulted in an augmented tolerance of S. sclerotiorum towards oxidative stress, and increased its sensitivity towards osmotic stress, indicative of the different roles of SsArf6 in various stress responses. Simultaneously, SsArf6 deletion led to an elevation in melanin accumulation. Moreover, the appressorium formation was severely impaired, and fungal virulence to host plants was significantly reduced. Overall, our findings demonstrate the essential role of SsArf6 in hyphal development, stress responses, appressorium formation, and fungal virulence to host plants.

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