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1.
Eur J Pharmacol ; 979: 176835, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39032764

RESUMEN

BACKGROUND: Mini-chromosome maintenance protein 2 (MCM2) is a potential target for the development of cancer therapeutics. However, small molecule inhibitors targeting MCM2 need further investigation. METHODS: Molecular dynamics simulation was performed to identify active pockets in the MCM2 protein structure (6EYC). The active pocket was used as a docking model to discover MCM2 inhibitors by using structure-based virtual screening and surface plasmon resonance (SPR) assay. Furthermore, the efficacy of pixantrone targeting MCM2 in ovarian cancer was evaluated in vitro and in vivo. RESULTS: Pixantrone was identified as a novel inhibitor of MCM2 by virtual screening. SPR binding affinity analysis confirmed the direct binding of pixantrone to MCM2 protein. Pixantrone significantly reduced the viability of ovarian cancer cells A2780 and SKOV3 in a dose- and time-dependent manner. In addition, pixantrone inhibited DNA replication, and induced cell cycle arrest and apoptosis in ovarian cancer cells via targeting MCM2. Knockdown of MCM2 could attenuate the inhibitory activity of pixantrone in ovarian cancer cells. Furthermore, pixantrone significantly suppressed ovarian cancer growth in the A2780 cell xenograft mouse model and showed favorable safety. CONCLUSION: These findings suggest that pixantrone may be a promising drug for ovarian cancer patients by targeting MCM2 in the clinic.

2.
Front Plant Sci ; 15: 1437107, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39040511

RESUMEN

Soybean quality and production are determined by seed viability. A seed's capacity to sustain germination via dry storage is known as its seed life. Thus, one of the main objectives for breeders is to preserve genetic variety and gather germplasm resources. However, seed quality and germplasm preservation have become significant obstacles. In this study, four artificially simulated aging treatment groups were set for 0, 24, 72, and 120 hours. Following an aging stress treatment, the transcriptome and metabolome data were compared in two soybean lines with notable differences in seed vigor-R31 (aging sensitive) and R80 (aging tolerant). The results showed that 83 (38 upregulated and 45 downregulated), 30 (19 upregulated and 11 downregulated), 90 (52 upregulated and 38 downregulated), and 54 (25 upregulated and 29 downregulated) DEGs were differentially expressed, respectively. A total of 62 (29 upregulated and 33 downregulated), 94 (49 upregulated and 45 downregulated), 91 (53 upregulated and 38 downregulated), and 135 (111 upregulated and 24 downregulated) differential metabolites accumulated. Combining the results of transcriptome and metabolome investigations demonstrated that the difference between R31 and R80 responses to aging stress was caused by genes related to phenylpropanoid metabolism pathway, which is linked to the seed metabolite caffeic acid. According to this study's preliminary findings, the aging-resistant line accumulated more caffeic acid than the aging-sensitive line, which improved its capacity to block lipoxygenase (LOX) activity. An enzyme activity inhibition test was used to demonstrate the effect of caffeic acid. After soaking seeds in 1 mM caffeic acid (a LOX inhibitor) for 6 hours and artificially aging them for 24 hours, the germination rates of the R31 and R80 seeds were enhanced. In conclusion, caffeic acid has been shown to partially mitigate the negative effects of soybean seed aging stress and to improve seed vitality. This finding should serve as a theoretical foundation for future research on the aging mechanism of soybean seeds.

3.
Adv Sci (Weinh) ; : e2403592, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39023171

RESUMEN

Endocrine-resistant ER+HER2- breast cancer (BC) is particularly aggressive and leads to poor clinical outcomes. Effective therapeutic strategies against endocrine-resistant BC remain elusive. Here, analysis of the RNA-sequencing data from ER+HER2- BC patients receiving neoadjuvant endocrine therapy and spatial transcriptomics analysis both show the downregulation of innate immune signaling sensing cytosolic DNA, which primarily occurs in endocrine-resistant BC cells, not immune cells. Indeed, compared with endocrine-sensitive BC cells, the activity of sensing cytosolic DNA through the cGAS-STING pathway is attenuated in endocrine-resistant BC cells. Screening of kinase inhibitor library show that this effect is mainly mediated by hyperactivation of AKT1 kinase, which binds to kinase domain of TBK1, preventing the formation of a trimeric complex TBK1/STING/IRF3. Notably, inactivation of cGAS-STING signaling forms a positive feedback loop with hyperactivated AKT1 to promote endocrine resistance, which is physiologically important and clinically relevant in patients with ER+HER2- BC. Blocking the positive feedback loop using the combination of an AKT1 inhibitor with a STING agonist results in the engagement of innate and adaptive immune signaling and impairs the growth of endocrine-resistant tumors in humanized mice models, providing a potential strategy for treating patients with endocrine-resistant BC.

4.
Nat Commun ; 15(1): 5852, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38992018

RESUMEN

The establishment of symbiotic interactions between leguminous plants and rhizobia requires complex cellular programming activated by Rhizobium Nod factors (NFs) as well as type III effector (T3E)-mediated symbiotic signaling. However, the mechanisms by which different signals jointly affect symbiosis are still unclear. Here we describe the mechanisms mediating the cross-talk between the broad host range rhizobia Sinorhizobium fredii HH103 T3E Nodulation Outer Protein L (NopL) effector and NF signaling in soybean. NopL physically interacts with the Glycine max Remorin 1a (GmREM1a) and the NFs receptor NFR5 (GmNFR5) and promotes GmNFR5 recruitment by GmREM1a. Furthermore, NopL and NF influence the expression of GmRINRK1, a receptor-like kinase (LRR-RLK) ortholog of the Lotus RINRK1, that mediates NF signaling. Taken together, our work indicates that S. fredii NopL can interact with the NF signaling cascade components to promote the symbiotic interaction in soybean.


Asunto(s)
Proteínas Bacterianas , Regulación de la Expresión Génica de las Plantas , Glycine max , Proteínas de Plantas , Sinorhizobium fredii , Simbiosis , Glycine max/microbiología , Glycine max/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Sinorhizobium fredii/metabolismo , Sinorhizobium fredii/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Transducción de Señal , Nodulación de la Raíz de la Planta/genética , Plantas Modificadas Genéticamente
5.
Int J Biol Sci ; 20(9): 3497-3514, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38993569

RESUMEN

Resistance to HER2-targeted therapy is the major cause of treatment failure in patients with HER2+ breast cancer (BC). Given the key role of immune microenvironment in tumor development, there is a lack of an ideal prognostic model that fully accounts for immune infiltration. In this study, WGCNA analysis was performed to discover the relationship between immune-related signaling and prognosis of HER2+ BC. After Herceptin-resistant BC cell lines established, transcriptional profiles of resistant cell line and RNA-sequencing data from GSE76360 cohort were analyzed for candidate genes. 85 samples of HER2+ BC from TCGA database were analyzed by the Cox regression, XGBoost and Lasso algorithm to generalize a credible immune-related prognostic index (IRPI). Correlations between the IRPI signature and tumor microenvironment were further analyzed by multiple algorithms, including single-cell RNA sequencing data analysis. Patients with high IRPI had suppressive tumor immune microenvironment and worse prognosis. The suppression of type I interferon signaling indicated by the IRPI in Herceptin-resistant HER2+ BC was validated. And we elucidated that the suppression of cGAS-STING pathway is the key determinant underlying immune escape in Herceptin-resistant BC with high IRPI. A combination of STING agonist and DS-8201 could serve as a new strategy for Herceptin-resistant HER2+ BC.


Asunto(s)
Neoplasias de la Mama , Resistencia a Antineoplásicos , Proteínas de la Membrana , Nucleotidiltransferasas , Receptor ErbB-2 , Trastuzumab , Microambiente Tumoral , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/inmunología , Femenino , Trastuzumab/uso terapéutico , Trastuzumab/farmacología , Resistencia a Antineoplásicos/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Nucleotidiltransferasas/metabolismo , Nucleotidiltransferasas/genética , Transducción de Señal , Línea Celular Tumoral , Pronóstico , Regulación Neoplásica de la Expresión Génica
6.
Int J Mol Sci ; 25(14)2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39062864

RESUMEN

The dimensions of organs such as flowers, leaves, and seeds are governed by processes of cellular proliferation and expansion. In soybeans, the dimensions of these organs exhibit a strong correlation with crop yield, quality, and other phenotypic traits. Nevertheless, there exists a scarcity of research concerning the regulatory genes influencing flower size, particularly within the soybean species. In this study, 309 samples of 3 soybean types (123 cultivar, 90 landrace, and 96 wild) were re-sequenced. The microscopic phenotype of soybean flower organs was photographed using a three-eye microscope, and the phenotypic data were extracted by means of computer vision. Pearson correlation analysis was employed to assess the relationship between petal and seed phenotypes, revealing a strong correlation between the sizes of these two organs. Through GWASs, SNP loci significantly associated with flower organ size were identified. Subsequently, haplotype analysis was conducted to screen for upstream and downstream genes of these loci, thereby identifying potential candidate genes. In total, 77 significant SNPs associated with vexil petals, 562 significant SNPs associated with wing petals, and 34 significant SNPs associated with keel petals were found. Candidate genes were screened by candidate sites, and haplotype analysis was performed on the candidate genes. Finally, the present investigation yielded 25 and 10 genes of notable significance through haplotype analysis in the vexil and wing regions, respectively. Notably, Glyma.07G234200, previously documented for its high expression across various plant organs, including flowers, pods, leaves, roots, and seeds, was among these identified genes. The research contributes novel insights to soybean breeding endeavors, particularly in the exploration of genes governing organ development, the selection of field materials, and the enhancement of crop yield. It played a role in the process of material selection during the growth period and further accelerated the process of soybean breeding material selection.


Asunto(s)
Flores , Estudio de Asociación del Genoma Completo , Glycine max , Fenotipo , Polimorfismo de Nucleótido Simple , Glycine max/genética , Glycine max/anatomía & histología , Glycine max/crecimiento & desarrollo , Flores/genética , Flores/anatomía & histología , Flores/crecimiento & desarrollo , Haplotipos , Sitios de Carácter Cuantitativo , Semillas/genética , Semillas/crecimiento & desarrollo , Semillas/anatomía & histología
7.
Sci Rep ; 14(1): 15994, 2024 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-38987328

RESUMEN

Mitigating pre-harvest sprouting (PHS) and post-harvest food loss (PHFL) is essential for enhancing food securrity. To reduce food loss, the use of plant derived specialized metabolites can represent a good approach to develop a more eco-friendly agriculture. Here, we have discovered that soybean seeds hidden underground during winter by Tscherskia triton and Apodemus agrarius during winter possess a higher concentration of volatile organic compounds (VOCs) compared to those remaining exposed in fields. This selection by rodents suggests that among the identified volatiles, 3-FurAldehyde (Fur) and (E)-2-Heptenal (eHep) effectively inhibit the growth of plant pathogens such as Aspergillus flavus, Alternaria alternata, Fusarium solani and Pseudomonas syringae. Additionally, compounds such as Camphene (Cam), 3-FurAldehyde, and (E)-2-Heptenal, suppress the germination of seeds in crops including soybean, rice, maize, and wheat. Importantly, some of these VOCs also prevent rice seeds from pre-harvest sprouting. Consequently, our findings offer straightforward and practical approaches to seed protection and the reduction of PHS and PHFL, indicating potential new pathways for breeding, and reducing both PHS and pesticide usage in agriculture.


Asunto(s)
Agricultura , Glycine max , Semillas , Compuestos Orgánicos Volátiles , Semillas/microbiología , Semillas/crecimiento & desarrollo , Compuestos Orgánicos Volátiles/metabolismo , Compuestos Orgánicos Volátiles/análisis , Compuestos Orgánicos Volátiles/farmacología , Animales , Glycine max/microbiología , Glycine max/crecimiento & desarrollo , Agricultura/métodos , Germinación , Productos Agrícolas/microbiología , Productos Agrícolas/crecimiento & desarrollo , Roedores/microbiología
8.
J Agric Food Chem ; 72(30): 17084-17098, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39013023

RESUMEN

Symbiotic nitrogen fixation carried out by the soybean-rhizobia symbiosis increases soybean yield and reduces the amount of nitrogen fertilizer that has been applied. MicroRNAs (miRNAs) are crucial in plant growth and development, prompting an investigation into their role in the symbiotic interaction of soybean with partner rhizobia. Through integrated small RNA, transcriptome, and degradome sequencing analysis, 1215 known miRNAs, 314 of them conserved, and 187 novel miRNAs were identified, with 44 differentially expressed miRNAs in soybean roots inoculated with Sinorhizobium fredii HH103 and a ttsI mutant. The study unveiled that the known miRNA gma-MIR398a-p5 was downregulated in the presence of the ttsI mutation, while the target gene of gma-MIR398a-p5, Glyma.06G007500, associated with nitrogen metabolism, was upregulated. The results of this study offer insights for breeding high-efficiency nitrogen-fixing soybean varieties, enhancing crop yield and quality.


Asunto(s)
Glycine max , Fijación del Nitrógeno , Sinorhizobium fredii , Simbiosis , Transcriptoma , Glycine max/microbiología , Glycine max/genética , Glycine max/metabolismo , Glycine max/crecimiento & desarrollo , Sinorhizobium fredii/genética , Sinorhizobium fredii/metabolismo , Sinorhizobium fredii/fisiología , Fijación del Nitrógeno/genética , MicroARNs/genética , MicroARNs/metabolismo , Regulación de la Expresión Génica de las Plantas , Raíces de Plantas/microbiología , ARN de Planta/genética , ARN de Planta/metabolismo
9.
Int J Mol Sci ; 25(11)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38891802

RESUMEN

Soybean, a major source of oil and protein, has seen an annual increase in consumption when used in soybean-derived products and the broadening of its cultivation range. The demand for soybean necessitates a better understanding of the regulatory networks driving storage protein accumulation and oil biosynthesis to broaden its positive impact on human health. In this study, we selected a chromosome segment substitution line (CSSL) with high protein and low oil contents to investigate the underlying effect of donor introgression on seed storage through multi-omics analysis. In total, 1479 differentially expressed genes (DEGs), 82 differentially expressed proteins (DEPs), and 34 differentially expressed metabolites (DEMs) were identified in the CSSL compared to the recurrent parent. Based on Gene Ontology (GO) term analysis and the Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG), integrated analysis indicated that 31 DEGs, 24 DEPs, and 13 DEMs were related to seed storage functionality. Integrated analysis further showed a significant decrease in the contents of the seed storage lipids LysoPG 16:0 and LysoPC 18:4 as well as an increase in the contents of organic acids such as L-malic acid. Taken together, these results offer new insights into the molecular mechanisms of seed storage and provide guidance for the molecular breeding of new favorable soybean varieties.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Glycine max , Semillas , Glycine max/genética , Glycine max/metabolismo , Semillas/genética , Semillas/metabolismo , Cromosomas de las Plantas/genética , Redes Reguladoras de Genes , Fitomejoramiento/métodos , Perfilación de la Expresión Génica/métodos , Ontología de Genes , Transcriptoma/genética , Multiómica
10.
Clin Transl Med ; 14(6): e1735, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38899748

RESUMEN

BACKGROUND: Mitochondrial outer membrane permeabilisation (MOMP) plays a pivotal role in cellular death and immune activation. A deeper understanding of the impact of tumour MOMP on immunity will aid in guiding more effective immunotherapeutic strategies. METHODS: A comprehensive pan-cancer dataset comprising 30 cancer-type transcriptomic cohorts, 20 immunotherapy transcriptomic cohorts and three immunotherapy scRNA-seq datasets was collected and analysed to determine the influence of tumour MOMP activity on clinical prognosis, immune infiltration and immunotherapy effectiveness. Leveraging 65 scRNA-Seq datasets, the MOMP signature (MOMP.Sig) was developed to accurately reflect tumour MOMP activity. The clinical predictive value of MOMP.Sig was explored through machine learning models. Integration of the MOMP.Sig model and a pan-cancer immunotherapy CRISPR screen further investigated potential targets to overcome immunotherapy resistance, which subsequently underwent clinical validation. RESULTS: Our research revealed that elevated MOMP activity reduces mortality risk in cancer patients, drives the formation of an anti-tumour immune environment and enhances the response to immunotherapy. This finding emphasises the potential clinical application value of MOMP activity in immunotherapy. MOMP.Sig, offering a more precise indicator of tumour cell MOMP activity, demonstrated outstanding predictive efficacy in machine-learning models. Moreover, with the assistance of the MOMP.Sig model, FOXO1 was identified as a core modulator that promotes immune resistance. Finally, these findings were successfully validated in clinical immunotherapy cohorts of skin cutaneous melanoma and triple-negative breast cancer patients. CONCLUSIONS: This study enhances our understanding of MOMP activity in immune modulation, providing valuable insights for more effective immunotherapeutic strategies across diverse tumours.


Asunto(s)
Inmunoterapia , Membranas Mitocondriales , Neoplasias , Humanos , Inmunoterapia/métodos , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Membranas Mitocondriales/metabolismo , Inmunomodulación/efectos de los fármacos
11.
J Hazard Mater ; 472: 134568, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38749246

RESUMEN

Cadmium (Cd) is a heavy metal that significantly impacts human health and the environment. Microorganisms play a crucial role in reducing heavy metal stress in plants; however, the mechanisms by which microorganisms enhance plant tolerance to Cd stress and the interplay between plants and microorganisms under such stress remain unclear. In this study, Oceanobacillus picturae (O. picturae) was isolated for interaction with soybean seedlings under Cd stress. Results indicated that Cd treatment alone markedly inhibited soybean seedling growth. Conversely, inoculation with O. picturae significantly improved growth indices such as plant height, root length, and fresh weight, while also promoting recovery in soil physiological indicators and pH. Metabolomic and transcriptomic analyses identified 157 genes related to aspartic acid, cysteine, and flavonoid biosynthesis pathways. Sixty-three microbial species were significantly associated with metabolites in these pathways, including pathogenic, adversity-resistant, and bioconductive bacteria. This research experimentally demonstrates, for the first time, the growth-promoting effect of the O. picturae strain on soybean seedlings under non-stress conditions. It also highlights its role in enhancing root growth and reducing Cd accumulation in the roots under Cd stress. Additionally, through the utilization of untargeted metabolomics, metagenomics, and transcriptomics for a multi-omics analysis, we investigated the impact of O. picturae on the soil microbiome and its correlation with differential gene expression in plants. This innovative approach unveils the molecular mechanisms underlying O. picturae's promotion of root growth and adaptation to Cd stress.


Asunto(s)
Cadmio , Glycine max , Plantones , Estrés Fisiológico , Glycine max/crecimiento & desarrollo , Glycine max/efectos de los fármacos , Glycine max/microbiología , Glycine max/metabolismo , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Cadmio/toxicidad , Estrés Fisiológico/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/microbiología , Raíces de Plantas/metabolismo , Bacillaceae/crecimiento & desarrollo , Bacillaceae/metabolismo , Bacillaceae/genética , Bacillaceae/efectos de los fármacos , Microbiología del Suelo
12.
Commun Biol ; 7(1): 613, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773248

RESUMEN

Understanding how to increase soybean yield is crucial for global food security. The genetic and epigenetic factors influencing seed size, a major crop yield determinant, are not fully understood. We explore the role of DNA demethylase GmDMEa in soybean seed size. Our research indicates that GmDMEa negatively correlates with soybean seed size. Using CRISPR-Cas9, we edited GmDMEa in the Dongnong soybean cultivar, known for small seeds. Modified plants had larger seeds and greater yields without altering plant architecture or seed nutrition. GmDMEa preferentially demethylates AT-rich transposable elements, thus activating genes and transcription factors associated with the abscisic acid pathway, which typically decreases seed size. Chromosomal substitution lines confirm that these modifications are inheritable, suggesting a stable epigenetic method to boost seed size in future breeding. Our findings provide insights into epigenetic seed size control and suggest a strategy for improving crop yields through the epigenetic regulation of crucial genes. This work implies that targeted epigenetic modification has practical agricultural applications, potentially enhancing food production without compromising crop quality.


Asunto(s)
Metilación de ADN , Elementos Transponibles de ADN , Glycine max , Semillas , Glycine max/genética , Semillas/genética , Semillas/crecimiento & desarrollo , Elementos Transponibles de ADN/genética , Epigénesis Genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética
13.
Int J Ophthalmol ; 17(3): 528-536, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38721515

RESUMEN

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.

14.
World J Clin Oncol ; 15(4): 531-539, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38689626

RESUMEN

Metastasis remains a major challenge in the successful management of malignant diseases. The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon, stomach, and pancreatic cancers, as well as melanoma, breast cancer, and sarcoma. As an important factor that influences the development of metastatic liver cancer, alternative splicing drives the diversity of RNA transcripts and protein subtypes, which may provide potential to broaden the target space. In particular, the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence, progression, aggressiveness, and drug resistance of cancers caused by the selective splicing of specific genes. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer. It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to these changes during metastasis.

15.
Nat Prod Res ; : 1-8, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38597194

RESUMEN

Sixteen triterpenoid saponins were isolated from the roots of Bupleurum scorzonerifolium Willd., including a new triterpenoid saponin and new natural saponin that was characterised by NMR for the first time, along with 14 known triterpenoid saponins. The structures of the compounds were established by 1D and 2D NMR spectroscopy, HR-ESI-MS, and comparison with the literature. The cytotoxic activity of the compounds against 4T1 cells was determined using the CCK8 method. Compounds 9 and 6 showed the strongest cytotoxic activity with IC50 values of 2.75 ± 0.86 and 3.78 ± 0.50 µM, respectively. Compounds 2-5 and 8 showed potent cytotoxic activity. Compounds 14 and 16 showed moderate cytotoxicity.

16.
J Hazard Mater ; 471: 134397, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38677114

RESUMEN

Biochar and organic compost are widely used in agricultural soil remediation as soil immobilization agents. However, the effects of biochar and compost on microbial community assembly processes in polluted soil under freezingthawing need to be further clarified. Therefore, a freezethaw cycle experiment was conducted with glyphosate (herbicide), imidacloprid (insecticide) and pyraclostrobin (fungicide) polluted to understand the effect of biochar and compost on microbial community assembly and metabolic behavior. We found that biochar and compost could significantly promote the degradation of glyphosate, imidacloprid and pyraclostrobin in freezethaw soil decrease the half-life of the three pesticides. The addition of immobilization agents improved soil bacterial and fungal communities and promoted the transformation from homogeneous dispersal to homogeneous selection. For soil metabolism, the combined addition of biochar and compost alleviated the pollution of glyphosate, imidacloprid and imidacloprid to soil through up-regulation of metabolites (DEMs) in amino acid metabolism pathway and down-regulation of DEMs in fatty acid metabolism pathway. The structural equation modeling (SEM) results showed that soil pH and DOC were the main driving factors affecting microbial community assembly and metabolites. In summary, the combined addition of biochar and compost reduced the adverse effects of pesticides residues.


Asunto(s)
Carbón Orgánico , Compostaje , Glicina , Glifosato , Herbicidas , Neonicotinoides , Nitrocompuestos , Microbiología del Suelo , Contaminantes del Suelo , Estrobilurinas , Neonicotinoides/metabolismo , Neonicotinoides/toxicidad , Nitrocompuestos/metabolismo , Nitrocompuestos/toxicidad , Estrobilurinas/metabolismo , Estrobilurinas/toxicidad , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/toxicidad , Carbón Orgánico/química , Glicina/análogos & derivados , Glicina/metabolismo , Glicina/toxicidad , Herbicidas/metabolismo , Herbicidas/toxicidad , Carbamatos/metabolismo , Carbamatos/toxicidad , Microbiota/efectos de los fármacos , Fungicidas Industriales/toxicidad , Fungicidas Industriales/metabolismo , Pirazoles/metabolismo , Pirazoles/toxicidad , Insecticidas/metabolismo , Insecticidas/toxicidad , Biodegradación Ambiental , Suelo/química , Bacterias/metabolismo , Bacterias/efectos de los fármacos
17.
Nat Prod Res ; : 1-8, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38587148

RESUMEN

Two novel phenylpropanoid amides, namely huomarenamide A (1) and huomarenamide B (2), along with twelve known compounds (3-14), were isolated from the seeds of Cannabis sativa L. The structures with absolute configurations of new compounds were unequivocally determined by spectroscopic analyses and the ECD method. The identification of the known compounds was based on a comparison of their 1D NMR data with literature references. All compounds were assessed for cytotoxic activity against LN229 cells, revealing that compounds 2, 13, and 14 exhibited significant cytotoxicity with IC50 values ranging from 9.02 to 21.26 µM.

18.
Plants (Basel) ; 13(6)2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38592937

RESUMEN

Soybean is the major global source of edible oils and vegetable proteins. Seed size and weight are crucial traits determining the soybean yield. Understanding the molecular regulatory mechanism underlying the seed weight and size is helpful for improving soybean genetic breeding. The molecular regulatory pathways controlling the seed weight and size were investigated in this study. The 100-seed weight, seed length, seed width, and seed weight per plant of a chromosome segment substitution line (CSSL) R217 increased compared with those of its recurrent parent 'Suinong14' (SN14). Transcriptomic and proteomic analyses of R217 and SN14 were performed at the seed developmental stages S15 and S20. In total, 2643 differentially expressed genes (DEGs) and 208 differentially accumulated proteins (DAPs) were detected at S15, and 1943 DEGs and 1248 DAPs were detected at S20. Furthermore, integrated transcriptomic and proteomic analyses revealed that mitogen-activated protein kinase signaling and cell wall biosynthesis and modification were potential pathways associated with seed weight and size control. Finally, 59 candidate genes that might control seed weight and size were identified. Among them, 25 genes were located on the substituted segments of R217. Two critical pathways controlling seed weight were uncovered in our work. These findings provided new insights into the seed weight-related regulatory network in soybean.

19.
Curr Issues Mol Biol ; 46(4): 3342-3352, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38666939

RESUMEN

Increasing the soybean-planting area and increasing the soybean yield per unit area are two effective solutions to improve the overall soybean yield. Northeast China has a large saline soil area, and if soybeans could be grown there with the help of isolated saline-tolerant rhizobia, the soybean cultivation area in China could be effectively expanded. In this study, soybeans were planted in soils at different latitudes in China, and four strains of rhizobia were isolated and identified from the soybean nodules. According to the latitudes of the soil-sampling sites from high to low, the four isolated strains were identified as HLNEAU1, HLNEAU2, HLNEAU3, and HLNEAU4. In this study, the isolated strains were identified for their resistances, and their acid and saline tolerances and nitrogen fixation capacities were preliminarily identified. Ten representative soybean germplasm resources in Northeast China were inoculated with these four strains, and the compatibilities of these four rhizobium strains with the soybean germplasm resources were analyzed. All four isolates were able to establish different extents of compatibility with 10 soybean resources. Hefeng 50 had good compatibility with the four isolated strains, while Suinong 14 showed the best compatibility with HLNEAU2. The isolated rhizobacteria could successfully establish symbiosis with the soybeans, but host specificity was also present. This study was a preliminary exploration of the use of salinity-tolerant rhizobacteria to help the soybean nitrogen fixation in saline soils in order to increase the soybean acreage, and it provides a valuable theoretical basis for the application of saline-tolerant rhizobia.

20.
Fitoterapia ; 175: 105902, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38492866

RESUMEN

Seven new triterpenoids, named Adeterpenoids A-G (1-7) and eight known compounds (8-15), were isolated from 70% ethanol extract of the roots of Adenophora tetraphylla (Thub.) Fisch. The compounds from it were separated by column chromatography techniques such as silica gel, ODS, and preparative liquid chromatography. Their structures were clarified based on extensive spectral analysis (1D, 2D-NMR, HR-ESI-MS, IR, UV, and CD) and comparison with the literature. At the same time, all compounds were evaluated for their cytotoxic activity against the LN229 (human glioma cell line). The results showed that compounds 2, 5, 6, 13, and 14 had a significant inhibitory effect on LN229 cells.


Asunto(s)
Antineoplásicos Fitogénicos , Raíces de Plantas , Triterpenos , Raíces de Plantas/química , Triterpenos/aislamiento & purificación , Triterpenos/farmacología , Triterpenos/química , Estructura Molecular , Línea Celular Tumoral , Humanos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , China
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