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AIMS: This study aimed to investigate the role of E2F1 in breast cancer biology. BACKGROUND: Expression of E2F1, a transcription factor of many oncogenes and tumor suppressor genes, is lowered in several malignancies, including breast carcinoma. OBJECTIVES: In the present study, we analyzed the status of E2F1 expression in association with diverse attributes of breast malignancy and its impact on cancer progression. METHODS: For this purpose, we used various freely available online applications for gene enrichment, expression, and methylation analysis to extract mutation-based E2F1 map, to measure E2F1 drug sensitivity, and to determine E2F1 association with DNA damage response proteins. RESULTS: Results revealed tissue-specific regulatory behavior of E2F1. Moreover, the key role of E2F1 in the promotion of metastasis, stem cell-mediated carcinogenesis, estrogen-mediated cell proliferation, and cellular defense system, has therefore highlighted it as a metaplastic marker and hot member of key resistome pathways. CONCLUSION: The information thus generated can be employed for future implications in devising rational therapeutic strategies. Moreover, this study has provided a more detailed insight into the diagnostic and prognostic potential of E2F1.
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Neoplasias , Humanos , Carcinogênese , Estrogênios , Proliferação de Células , Resistência a Medicamentos , Fator de Transcrição E2F1/genéticaRESUMO
Cadmium (Cd) toxicity can significantly limit plant growth and development. To eliminate the toxic effects of Cd stress, we intended to evaluate the biochemical mediated physiological responses in maize treated with biostimulant and zinc oxide nanoparticles (ZnPs). In silico analysis exhibited that the maize treated with Cd stress (200 µM) had an adverse impact on CAT1, CAT2, CAT3 and gor1 proteins, which are influential in managing the machinery of redox homeostasis. While maize inoculated with bacteria-based biostimulant and ZnPs (10 ppm) showed prominently improved biomass, chlorophyll a, b and carotenoid content. We found a significant increase in the total sugar, protein, proline content and antioxidants under the effect of Cd stress. However, these parameters are further enhanced by applying biostimulants and ZnPs. Declined lipid peroxidation and membrane solubilization index under the effect of biostimulant and ZnPs was observed. Furthermore, these treatments improved maize's zinc, copper, sodium, magnesium, iron, potassium and calcium content. Based on these results, an antagonistic relationship between Zn and Cd uptake that triggered efficient Cd detoxification in maize shoot was found. Scanning electron micrography showed distorted leaf structure of the Cd stressed plants while the biostimulant and ZnPs reduced the structural cell damage of maize leaves. In silico study showed that ZnO positively regulates all protein interactors, including GRMZM2G317386_P01 (Metallo endo proteinase 1-MMP), GRMZM2G110220_P01 (Metallo endo proteinase 5-MMP), GRMZM2G103055_P01 (Alpha-amylase) and GRMZM2G006069_P01 (Zn-dependent exo peptidase superfamily) proteins which are involved in energy generating processes, channels formation, matrix re-localization and stress response. This suggests that ZnO offers an ideal role with protein interactors in maize. Our findings depict that these treatments, i.e., biostimulant and ZnPs alone, are efficient enough to exhibit Cd remediation potential in maize; however, their combination showed synergistic effects.
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Nanopartículas , Poluentes do Solo , Óxido de Zinco , Cádmio/análise , Zea mays/metabolismo , Óxido de Zinco/toxicidade , Óxido de Zinco/metabolismo , Poluentes do Solo/análise , Clorofila A/metabolismo , Nanopartículas/toxicidade , Nanopartículas/química , Peptídeo Hidrolases/metabolismoRESUMO
BACKGROUND: Glioblastoma (GBM) harbors significant genetic heterogeneity, high infiltrative capacity, and patterns of relapse following many therapies. The expression of nuclear factor kappa-B (NF-κB p65 (RelA)) and signaling pathways is constitutively activated in GBM through inflammatory stimulation such as tumor necrosis factor-alpha (TNFα), cell invasion, motility, abnormal physiological stimuli, and inducible chemoresistance. However, the underlying anti-tumor and anti-proliferative mechanisms of NF-κB p65 (RelA) and TNFα are still poorly defined. This study aimed to investigate the expression profiling of NF-κB p65 (RelA) and TNFα as well as the effectiveness of celecoxib along with temozolomide (TMZ) in reducing the growth of the human GBM cell line SF-767. METHODS: genome-wide expression profiling, enrichment analysis, immune infiltration, quantitative expression, and the Microculture Tetrazolium Test (MTT) proliferation assay were performed to appraise the effects of celecoxib and TMZ. RESULTS: demonstrated the upregulation of NF-κB p65 (RelA) and TNFα and celecoxib reduced the viability of the human glioblastoma cell line SF-767, cell proliferation, and NF-κB p65 (RelA) and TNFα expression in a dose-dependent manner. Overall, these findings demonstrate for the first time how celecoxib therapy could mitigate the invasive characteristics of the human GBM cell line SF-767 by inhibiting the NF-κB mediated stimulation of the inflammatory cascade. CONCLUSION: based on current findings, we propose that celecoxib as a drug candidate in combination with temozolomide might dampen the transcriptional and enzymatic activities associated with the aggressiveness of GBM and reduce the expression of GBM-associated NF-κB p65 (RelA) and TNFα inflammatory genes expression.
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Rhizoctonia solani (RS) is a pathogenic fungus that affects maize (Zea mays L.) plants and causes banded leaf and sheath blight (BLSB) with severe consequences leading to significant economic losses. Contrarily, rhizobacteria produce numerous volatile organic compounds (VOCs) that help in devising the environment-friendly mechanism for promoting plant growth and stress alleviation without having physical contact with plants. In the present study, 15 rhizobacterial strains were tested for their antagonism against RS. The antagonistic potential of VOCs of the tested plant growth-promoting rhizobacteria (PGPR) strains ranged from 50% to 80% as compared to the control (without PGPR). Among these 15 strains, the maximum (80%) antagonistic activity was exhibited by Pseudomonas pseudoalcaligenes SRM-16. Thus, the potential of VOCs produced by P. pseudoalcaligenes SRM-16 to alleviate the BLSB disease in maize was evaluated. A pot experiment was conducted under greenhouse conditions to observe the effect of VOCs on disease resistance of BLSB-infected seedlings. Overall, maize seedlings exposed to VOCs showed a significant increase in disease resistance as indicated by a reduced disease score than that of unexposed infected plants. The VOCs-exposed maize exhibited lower (11.6%) disease incidence compared to the non-inoculated maize (14.1%). Moreover, plants exposed to VOCs displayed visible improvements in biomass, photosynthetic pigments, osmoregulation, and plant antioxidant and defense enzyme activities compared to the healthy but unexposed seedlings. Simultaneous application of RS and VOCs enhanced superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), phenylalanine ammonia lyase (PAL), ascorbate peroxidase (APX), and polyphenol oxidase (PPO) activities by 96.7%, 266.6%, 313.7%, 246.6%, 307%, and 149.7%, respectively, in the roots and by 81.6%, 246.4%, 269.5%, 269.6%, 329%, and 137.6%, respectively, in the shoots, relative to those of the control plants. The binding affinity of the VOCs (2-pentylfuran, 2,3-butanediol, and dimethyl disulfide) with CRZ1 and S9 protein receptors of RS was assessed by deploying in silico methods. Overall, 2-pentylfuran exhibited a binding affinity with both the selected receptors of RS, while 2,3-butanediol and dimethyl disulfide were able to bind S9 protein only. Hence, it can be deduced that S9 protein receptors are more likely the target RS receptors of bacterial VOCs to inhibit the proliferation of RS.
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The efficiency of Cd-tolerant plant growth-promoting bacteria (PGPB), zinc oxide nanoparticles (ZnO NPs), and titanium dioxide nanoparticles (TiO2) in maize growing in Cd-rich conditions was tested in the current study. The best Cd-tolerant strain, Bacillus pumilus, exhibited plant growth stimulation in vivo and in vitro experiments. We determined the toxic concentrations (30 (ppm)) of both NPs for plant growth. B. pumilus, ZnO NPs (20 (ppm)), and TiO2 NPs (10 (ppm)) had a synergistic effect on plant growth promotion in Cd-contaminated soil (120 (ppm)) in a pot experiment. Both alone and in combination, these therapies reduced Cd toxicity, resulting in improved stress metabolism and defense responses. The combined treatments showed increased relative water content, photosynthetic pigments, proline, total sugars, and proteins and significantly reduced lipid peroxidation. Moreover, this combination increased the levels of minerals and antioxidants and reduced Cd bioaccumulation in shoots and roots by 40-60%. Our in silico pipeline presented a novel picture of the participation of ZnO-TiO2 protein interaction in both B. pumilus and maize. These findings provide fresh insights on the use of B. pumilus, ZnO, and TiO2 NPs, both separately and in combination, as a viable and environmentally benign strategy for reducing Cd stress in maize.
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During this study, the bioremediation potential of zinc-oxide nanoparticles (ZnO-NPs) and PGPR mixed biofertilizer (BF) on maize plants under induced arsenic (As) stress of 50 ppm and 100 ppm was investigated. The treated plants showed increased As resistance to mitigate the adverse effects of stress by enhancing fresh and dry biomass, relative water content, protein content, soluble sugars, proline content, enzymatic antioxidant defense mechanisms including activities of catalase (CAT), peroxidase (POD), ascorbate peroxidase (APX), superoxide dismutase (SOD), and malondialdehyde (MDA) content. In the pot experiment, the parameters studied have shown that the integrated treatments of ZnO-NPs and BF cause a notable enhancement in relative water content 43%-50% and plant biomass. Moreover, the same treatment showed a marked upregulation in enzymes activity (APX, SOD, APX, and CAT) which oxidized the cell-damaging ROS, produced in response to As stress. Likewise, the combined treatment showed a maximum reduction in MDA content 46%-57% and electrolyte leakage in As treated plants as compared to stressed plants. On the other hand, total soluble sugar 114%-170% and total protein content 117%-241% escalated. SEM analysis revealed marked damage reduction in the treated cells caused by arsenic toxicity. Thus, the use of BF comprised of rhizobacteria along with ZnO-NPs could be a very effective bio source for improving maize plant growth under As stress. In in silico study, As mediated network of proteins showed positive and negative regulation of As activity that leads to stress generation for housekeeping genome.