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1.
Nature ; 623(7986): 432-441, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37914932

RESUMEN

Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis1-4. Although the genetic contributions to oncogenic transitions have been investigated, epigenetic drivers remain less understood. Here we constructed a pan-cancer epigenetic and transcriptomic atlas using single-nucleus chromatin accessibility data (using single-nucleus assay for transposase-accessible chromatin) from 225 samples and matched single-cell or single-nucleus RNA-sequencing expression data from 206 samples. With over 1 million cells from each platform analysed through the enrichment of accessible chromatin regions, transcription factor motifs and regulons, we identified epigenetic drivers associated with cancer transitions. Some epigenetic drivers appeared in multiple cancers (for example, regulatory regions of ABCC1 and VEGFA; GATA6 and FOX-family motifs), whereas others were cancer specific (for example, regulatory regions of FGF19, ASAP2 and EN1, and the PBX3 motif). Among epigenetically altered pathways, TP53, hypoxia and TNF signalling were linked to cancer initiation, whereas oestrogen response, epithelial-mesenchymal transition and apical junction were tied to metastatic transition. Furthermore, we revealed a marked correlation between enhancer accessibility and gene expression and uncovered cooperation between epigenetic and genetic drivers. This atlas provides a foundation for further investigation of epigenetic dynamics in cancer transitions.


Asunto(s)
Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Neoplasias , Humanos , Hipoxia de la Célula , Núcleo Celular , Cromatina/genética , Cromatina/metabolismo , Elementos de Facilitación Genéticos/genética , Epigénesis Genética/genética , Transición Epitelial-Mesenquimal , Estrógenos/metabolismo , Perfilación de la Expresión Génica , Proteínas Activadoras de GTPasa/metabolismo , Metástasis de la Neoplasia , Neoplasias/clasificación , Neoplasias/genética , Neoplasias/patología , Secuencias Reguladoras de Ácidos Nucleicos/genética , Análisis de la Célula Individual , Factores de Transcripción/metabolismo
2.
BMC Plant Biol ; 24(1): 756, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39107683

RESUMEN

BACKGROUND: Tobacco mosaic virus (TMV) is a highly infectious plant virus that affects a wide variety of plants and reduces crop yields around the world. Here, we assessed the effectiveness of using Ammi visnaga aqueous seed extract to synthesize silver nanoparticles (Ag-NPs) and their potential to combat TMV. Different techniques were used to characterize Ag-NPs, such as scanning and transmission electron microscopy (SEM, TEM), energy-dispersive X-ray spectroscopy (EDS), fourier transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS). RESULTS: TEM demonstrated that the synthesized Ag-NPs had a spherical form with an average size of 23-30 nm and a zeta potential value of -15.9 mV, while FTIR revealed various functional groups involved in Ag-NP stability and capping. Interestingly, the Pre-treatment of tobacco plants (protective treatment) with Ag-NPs at 100-500 µg/mL significantly suppressed viral symptoms, while the Post-treatment (curative treatment) delayed their appearance. Furthermore, protective and curative treatments significantly increased chlorophyll a and b, total flavonoids, total soluble carbohydrates, and antioxidant enzymes activity (PPO, POX and CAT). Simultaneously, the application of Ag-NPs resulted in a decrease in levels of oxidative stress markers (H2O2 and MDA). The RT-qPCR results and volcano plot analysis showed that the Ag-NPs treatments trigger and regulate the transcription of ten defense-related genes (SbWRKY-1, SbWRKY-2, JERF-3, GST-1, POD, PR-1, PR-2, PR-12, PAL-1, and HQT-1). The heatmap revealed that GST-1, the primary gene involved in anthocyanidin production, was consistently the most expressed gene across all treatments throughout the study. Analysis of the gene co-expression network revealed that SbWRKY-19 was the most central gene among the studied genes, followed by PR-12 and PR-2. CONCLUSIONS: Overall, the reported antiviral properties (protective and/or curative) of biosynthesized Ag-NPs against TMV lead us to recommend using Ag-NPs as a simple, stable, and eco-friendly agent in developing pest management programs against plant viral infections.


Asunto(s)
Nanopartículas del Metal , Nicotiana , Enfermedades de las Plantas , Extractos Vegetales , Plata , Virus del Mosaico del Tabaco , Virus del Mosaico del Tabaco/fisiología , Plata/farmacología , Enfermedades de las Plantas/virología , Enfermedades de las Plantas/genética , Extractos Vegetales/farmacología , Nicotiana/genética , Nicotiana/virología , Resistencia a la Enfermedad/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas
3.
BMC Plant Biol ; 24(1): 818, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39215238

RESUMEN

This study investigates the differential responses of two maize genotypes, SC180 and SC168, to salt stress, aiming to elucidate the mechanisms underlying salinity tolerance and identify traits associated with improved stress resilience. Salinity stress, imposed by 150 mM NaCl, adversely affected various growth parameters in both genotypes. SC180 exhibited a more pronounced reduction in shoot length (13.6%) and root length (13.6%) compared to SC168, which showed minimal reductions (3.0% and 2.3%, respectively). Additionally, dry weight losses in SC180's leaves, stems, and roots were significantly greater than those in SC168. Under salinity stress, both genotypes accumulated Na+ in all organs, with SC168 showing higher Na + concentrations. However, K+ levels decreased more significantly in SC180's leaves than in SC168's. The study also assessed physiological responses, noting that SC180 experienced a substantial reduction in relative water content (RWC) in leaves (22.7%), while SC168's RWC remained relatively stable (5.15%). Proline accumulation, a marker for osmotic adjustment, increased 2.3-fold in SC168 compared onefold in SC180. Oxidative stress indicators, such as electrolyte leakage and hydrogen peroxide levels, were elevated in both genotypes under salt stress, with SC180 showing higher increases (48.5% and 48.7%, respectively) than SC168 (35.25% and 22.0%). Moreover, antioxidant enzymes (APX, CAT, POD, SOD, GR) activities were significantly enhanced in SC168 under salinity stress, whereas SC180 showed no significant changes in these activities. Stress indices, used to quantify and compare salinity tolerance, consistently ranked SC168 as more tolerant (average rank = 1.08) compared to SC180 (average rank = 1.92). Correlation analyses further confirmed that SC168's superior tolerance was associated with better Na + regulation, maintenance of K+ levels, and a robust antioxidant defense system. In conclusion, SC168 demonstrated greater resilience to salinity stress, attributed to its efficient ion regulation, stable water status, enhanced osmotic adjustment, and strong antioxidant response. These findings provide valuable insights for breeding and developing salinity-tolerant maize varieties.


Asunto(s)
Antioxidantes , Genotipo , Tolerancia a la Sal , Zea mays , Zea mays/genética , Zea mays/fisiología , Zea mays/crecimiento & desarrollo , Zea mays/metabolismo , Antioxidantes/metabolismo , Tolerancia a la Sal/genética , Sodio/metabolismo , Estrés Oxidativo , Hojas de la Planta/fisiología , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Potasio/metabolismo
4.
BMC Plant Biol ; 23(1): 388, 2023 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-37563704

RESUMEN

BACKGROUND: Stripe rust is considered one of the most devastating diseases of wheat all over the world, resulting in a high loss in its production. In this study, time-course changes in expression of the polyphenol biosynthesis pathways genes in wheat against stripe rust were investigated. The defense mechanisms triggered by mycorrhizal colonization and/or spraying with Streptomyces viridosporus HH1 against this disease were also investigated. RESULTS: Results obtained revealed that C3H, which is considered the key gene in lignin biosynthesis, was the most expressed gene. Furthermore, most of the chlorogenic acid and flavonoid biosynthesis genes were also overexpressed. Volcano plots of the studied genes reveal that the dual treatment led to a high significant overexpression of 10 out of the 13 studied genes. Heatmap of these genes showed that the most frequent expressed gene in response to all applied treatments along the study period was DFR, the key gene in the biosynthesis of anthocyanidins. Gene co-expression network of the studied genes showed that HQT was the most central gene with respect to the other genes, followed by AN2 and DFR, respectively. Accumulation of different flavonoids and phenolic acids were detected in response to the dual treatment, in particular, cinnamic acid, coumarin, and esculetin, which recorded the highest elevation level recording 1000, 488.23, and 329.5% respectively. Furthermore, results from the greenhouse experiment showed that application of the dual treatment led to an 82.8% reduction in the disease severity, compared with the control treatment. CONCLUSIONS: We can conclude that the biosynthesis of lignin, chlorogenic acid, and flavonoids contributed to the synergistic triggering effect of the dual treatment on wheat resistance to stripe rust.


Asunto(s)
Basidiomycota , Micorrizas , Triticum/genética , Polifenoles , Ácido Clorogénico , Lignina , Basidiomycota/fisiología , Flavonoides , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética
5.
Artículo en Inglés | MEDLINE | ID: mdl-30617094

RESUMEN

We analyzed the impact of vancomycin (VAN) combined with adjuvant ß-lactam therapy (Combo) on persistent (≥5 days) methicillin-resistant Staphylococcus aureus bacteremia versus VAN alone by using pooled data from two previously published observational studies (n = 156). Combo was inversely associated with persistent bacteremia (adjusted odds ratio, 0.460; 95% confidence interval, 0.229 to 0.923). Acute kidney injury was more common with Combo than with VAN (18.9% and 7.6%, respectively; P = 0.062).


Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infecciones Estafilocócicas/tratamiento farmacológico , Vancomicina/uso terapéutico , beta-Lactamas/uso terapéutico , Lesión Renal Aguda/inducido químicamente , Antibacterianos/efectos adversos , Bacteriemia/microbiología , Quimioterapia Combinada , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Observacionales como Asunto , Estudios Retrospectivos , Resultado del Tratamiento , Vancomicina/efectos adversos , beta-Lactamas/efectos adversos
6.
Cells ; 13(8)2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38667314

RESUMEN

The clinical management of bladder cancer continues to present significant challenges. Bacillus Calmette-Guérin (BCG) immunotherapy remains the gold standard of treatment for non-muscle invasive bladder cancer (NMIBC), but many patients develop recurrence and progression to muscle-invasive disease (MIBC), which is resistant to BCG. This review focuses on the immune mechanisms mobilized by BCG in bladder cancer tumor microenvironments (TME), mechanisms of BCG resistance, the dual role of the BCG-triggered NFkB/TNFα/PGE2 axis in the regulation of anti-tumor and tumor-promoting aspects of inflammation, and emerging strategies to modulate their balance. A better understanding of BCG resistance will help develop new treatments and predictive biomarkers, paving the way for improved clinical outcomes in bladder cancer patients.


Asunto(s)
Vacuna BCG , Inmunoterapia , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/terapia , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Humanos , Microambiente Tumoral/inmunología , Vacuna BCG/uso terapéutico , Vacuna BCG/inmunología , Inmunoterapia/métodos , Animales
7.
Plants (Basel) ; 13(11)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38891271

RESUMEN

Wheat is one of the most important cereal crops in Egypt and all over the world. Its productivity is adversely affected by drought due to deficient irrigation to provide nutrients required for plant growth. In a field experiment, silicon foliar applications at concentrations of 0, 200, and 400 mg L-1 were performed at different irrigation rates ranging from 1000 to 4000 m3 ha-1 to assess water irrigation productivity and wheat crop yield in a calcareous soil under arid climate conditions. Increased irrigation rates led to a significant increase in soil nutrient dynamics, as well as in the number and weight of grains per spike, leaf area index, grain yield, straw yield, and biological yield, with the exception of the weight of 1000 grains. Spraying with sodium silicate had a significant impact on grain yield and harvest index but did not significantly impact the other traits. Furthermore, the interaction between irrigation and silicate application rates showed significance only for grain yield, the number of spikes/m2, and the harvest index. Applying three times irrigation could produce the highest nutrient retention, wheat yield, and water irrigation productivity. No significance was observed between 3000 m3 ha-1 and 4000 m3 ha-1 irrigation, indicating a saving of 25% of applied irrigation water. It can be concluded that applying irrigation at 3000 m3 ha-1 could be a supplemental irrigation strategy. High wheat grain yield can be achieved under deficit irrigation (3000 m3 ha-1) on the northwestern coast of Egypt with an arid climate by spraying crops with sodium silicate at a rate of 400 mg L-1.

8.
ACS Omega ; 9(11): 13086-13099, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38524478

RESUMEN

Addressing industrial wastewater treatment challenges and removing hazardous organic pollutants, such as carcinogenic methyl orange (MO) and azo dyes, is a pressing concern. This study explores the use of the Zea mays envelope, an agricultural waste product, to produce Z. mays activated carbon (ZMAC) through the chemical activation of maize envelopes with phosphoric acid. Various analytical techniques, including FTIR, XRD, TGA, DSC, and SEM, characterize ZMAC. Results show that ZMAC exhibits an impressive monolayer adsorption capacity of 66.2 mg/g for MO. The Langmuir isotherm model fits the experimental data well, indicating monolayer coverage of the MO on the ZMAC surface. The pH-sensitive adsorption process demonstrates an optimal removal efficiency at pH 4. ZMAC follows the pseudo-second-order kinetic model, and diffusion rate constant analysis identifies three consecutive stages in the adsorption process. Moreover, the uptake of MO ions by ZMAC is identified as an exothermic and spontaneous process. Reusability tests demonstrate efficient regeneration of ZMAC up to five times with 1 mL of 2 M HNO3 in each cycle, without sorbent mass loss. Thermodynamic analysis shows an increase in the uptake capacity from 66.2 to 73.2 mg/g with temperature elevation. This study offers practical solutions for industrial wastewater treatment challenges, providing an environmentally sustainable and effective approach to mitigate the risks associated with hazardous organic pollutants.

9.
Int J Biol Macromol ; 270(Pt 2): 132252, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38729503

RESUMEN

In this study, we developed a novel nanocomposite by synthesizing zinc (ZnNPs), copper (CuNPs), and silver (AgNPs) nanoparticles using olive leaf extract and incorporating them into a chitosan polymer. This approach combines the biocompatibility of chitosan with the antimicrobial and anticancer properties of metal nanoparticles, enhanced by the phytochemical richness of olive leaf extract. The significance of our research lies in its potential to offer a biodegradable and stable alternative to conventional antibiotics and cancer treatments, particularly in combating multidrug-resistant bacteria and various cancer types. Comprehensive characterization through Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray (EDX), and Transmission Electron Microscopy (TEM) confirmed the successful synthesis of the nanocomposites, with an average size of ~22.6 nm. Phytochemical analysis highlighted the antioxidant-rich composition of both the olive leaf extract and the nanoparticles themselves. Functionally, the synthesized nanoparticles exhibited potent antimicrobial activity against multidrug-resistant bacterial strains, outperforming traditional antibiotics by inhibiting key resistance genes (ermC, tetX3-q, blaZ, and Ery-msrA). In anticancer assessments, the nanoparticles showed selective cytotoxicity towards cancer cells in a concentration-dependent manner, with CuNPs and AgNPs showing particularly strong anticancer effects, while demonstrating minimal toxicity towards normal cells. ZnNPs were noted for their low cytotoxicity, highlighting the safety profile of these nanoparticles. Further, the nanoparticles induced apoptosis in cancer cells, as evidenced by the modulation of oncogenes (P21, P53, and BCL2), suggesting their therapeutic potential. The findings of our study underscore the versatile applications of these biogenic nanoparticles in developing safer and more effective antimicrobial and anticancer therapies.


Asunto(s)
Antineoplásicos , Quitosano , Tecnología Química Verde , Nanopartículas del Metal , Nanocompuestos , Olea , Extractos Vegetales , Hojas de la Planta , Quitosano/química , Quitosano/farmacología , Nanocompuestos/química , Olea/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Humanos , Hojas de la Planta/química , Nanopartículas del Metal/química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antiinfecciosos/síntesis química , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Plata/química , Plata/farmacología , Línea Celular Tumoral
10.
Plant Physiol Biochem ; 207: 108421, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38335887

RESUMEN

Plant fungal diseases impose a formidable challenge for global agricultural productivity, a meticulous examination of host-pathogen interactions. In this intricate study, an exhaustive investigation was conducted on infected tomatoes obtained from Egyptian fields, leading to the precise molecular identification of the fungal isolate as Alternaria alternata (OP881811), and the isolate showed high identity with Chinese isolates (ON973896 and ON790502). Subsequently, fourteen diverse tomato cultivars; Cv Ferment, Cv 103, Cv Damber, Cv 186, Cv 4094, Cv Angham, Cv N 17, Cv Gesma, Cv 010, Cv branch, cv 2020, Cv 023, Cv Gana and Cv 380 were meticulously assessed to discern their susceptibility levels upon inoculation with Alternaria alternata. Thorough scrutiny of disease symptom manifestation and the extent of tomato leaf damage ensued, enabling a comprehensive evaluation of cultivar responses. Results unveiled a spectrum of plant susceptibility, with three cultivars exhibiting heightened vulnerability (Cv Ferment, Cv 103 and Cv Damber), five cultivars displaying moderate susceptibility (Cv 186, Cv 4094, Cv Angham, Cv N 17 and Cv Gesma), and six cultivars demonstrating remarkable resilience to the pathogen (Cv 010, Cv branch, cv, 2020; Cv 023, Cv Gana and Cv 380). In order to gain a thorough understanding of the underlying physiological patterns indicative of plant resistance against A. alternata, an in-depth exploration of polyphenols, flavonoids, and antioxidant enzymes ensued. These key indicators were closely examined, offering valuable insights into the interplay between plant physiology and pathogen response. Robust correlations emerged, with higher contents of these compounds correlating with heightened susceptibility, while lower levels were indicative of enhanced plant tolerance. In tandem with the physiological assessment, a thorough investigation of four pivotal defensive genes (PR5, PPO, PR3, and POX) was undertaken, employing cutting-edge Real-Time PCR technology. Gene expression profiles displayed intriguing variations across the evaluated tomato cultivars, ultimately facilitating the classification of cultivars into distinct groups based on their levels of resistance, moderate susceptibility, or heightened sensitivity. By unravelling the intricate dynamics of plant susceptibility, physiological responses, and patterns of gene expression, this comprehensive study paves the way for targeted strategies to combat plant fungal diseases. The findings contribute valuable insights into host-pathogen interactions and empower agricultural stakeholders with the knowledge required to fortify crop resilience and safeguard global food security.


Asunto(s)
Micosis , Solanum lycopersicum , Solanum lycopersicum/genética , Estrés Fisiológico , Alternaria
11.
Front Plant Sci ; 14: 1108977, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37063192

RESUMEN

Water scarcity is a crucial environmental stress that constrains rice growth and production. Thus, breeding for developing high-yielding and drought-tolerant rice genotypes is decisive in sustaining rice production and ensuring global food security, particularly under stress conditions. To this end, this study was conducted to evaluate the effects of water deficit on 31 genotypes of rice (seven lines, viz., Puebla, Hispagran, IET1444, WAB1573, Giza177, Sakha101, and Sakha105, and three testers, viz., Sakha106, Sakha107, and Sakha108) and their 21 crosses produced by line × tester mating design under normal and water deficit conditions; this was to estimate the combining ability, heterosis, and gene action for some traits of physiological, biochemical, and yield components. This study was performed during the summer seasons of 2017 and 2018. The results showed that water deficit significantly decreased relative water content, total chlorophyll content, grain yield, and several yield attributes. However, osmolyte (proline) content and antioxidant enzyme activities (CAT and APX) were significantly increased compared with the control condition. Significant mean squares were recorded for the genotypes and their partitions under control and stress conditions, except for total chlorophyll under normal irrigation. Significant differences were also detected among the lines, testers, and line × tester for all the studied traits under both irrigation conditions. The value of the σ²GCA variance was less than the value of the σ²SCA variance for all the studied traits. In addition, the dominance genetic variance (σ2D) was greater than the additive genetic variance (σ2A) in controlling the inheritance of all the studied traits under both irrigation conditions; this reveals that the non-additive gene effects played a significant role in the genetic expression of the studied traits. The two parental genotypes (Puebla and Hispagran) were identified as good combiners for most physiological and biochemical traits, earliness, shortness, grain yield, and 1,000-grains weight traits. Additionally, the cross combinations Puebla × Sakha107, Hispagran × Sakha108, and Giza177 × Sakha107 were the most promising. These results demonstrated the substantial and desirable specific combining ability effects on all the studied traits, which suggested that it could be considered for use in rice hybrid breeding programs.

12.
PeerJ ; 11: e16256, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38152345

RESUMEN

Salinity stress poses a major challenge to agricultural productivity worldwide, and understanding their responses at the early growth stage is vital for devising strategies to cope with this stress. Therefore, to improve triticale productivity, this study investigated the salinity stress tolerance of different salt-tolerant triticale genotypes aiming to cultivate them on saline soils. To this end, salinity stress impacts on nine triticale genotypes, i.e., Zhongsi 1084, Gannong No. 2, Gannong No. 4, Shida No. 1, C6, C16, C23, C25 and C36 at germination and early seedling stages was evaluated. Each genotype was subjected to six treatments inducing control, 40, 80, 120, 160, and 200 mM NaCl treatments to study their effect on seedling and termination traits of the nine genotypes. Compared to the overall mean seedling vigor index, the seedling vigor index was higher in the genotypes Zhongsi 1084 and C6 (39% and 18.1%, respectively) and lower in Gannong No.2 (41%). Increasing NaCl concentrations negatively affected germination and seedling traits. Compared to other genotypes, Zhongsi 1084 had the highest mean germination rate, germination vigor index, germination percentage, mean daily germination and germination energy. It also showed the lowest relative salt injury. The relative salt injury was higher in the genotype Shida No. 1 than those in Gannong No. 2, Gannong No. 4, Shida No. 1, C16, and C36 genotypes. All genotypes exhibited desirable mean germination time except for line C6. High significant positive correlations were observed among germination rate, germination vigor index, germination percentage, mean daily germination, seedling vigor index, and root length. Principal component analysis (PCA) grouped the most desirable genotypes into two clusters. Our study determined salt stress tolerance of nine triticale genotypes at germination and early seedling stages. to select salt-tolerant genotypes that can be cultivated on saline soil or after salt irrigation.


Asunto(s)
Plantones , Triticale , Plantones/genética , Germinación/genética , Cloruro de Sodio/farmacología , Suelo , Genotipo
13.
Cancer Res ; 83(8): 1214-1233, 2023 04 14.
Artículo en Inglés | MEDLINE | ID: mdl-36779841

RESUMEN

Multiple myeloma (MM) is a highly refractory hematologic cancer. Targeted immunotherapy has shown promise in MM but remains hindered by the challenge of identifying specific yet broadly representative tumor markers. We analyzed 53 bone marrow (BM) aspirates from 41 MM patients using an unbiased, high-throughput pipeline for therapeutic target discovery via single-cell transcriptomic profiling, yielding 38 MM marker genes encoding cell-surface proteins and 15 encoding intracellular proteins. Of these, 20 candidate genes were highlighted that are not yet under clinical study, 11 of which were previously uncharacterized as therapeutic targets. The findings were cross-validated using bulk RNA sequencing, flow cytometry, and proteomic mass spectrometry of MM cell lines and patient BM, demonstrating high overall concordance across data types. Independent discovery using bulk RNA sequencing reiterated top candidates, further affirming the ability of single-cell transcriptomics to accurately capture marker expression despite limitations in sample size or sequencing depth. Target dynamics and heterogeneity were further examined using both transcriptomic and immuno-imaging methods. In summary, this study presents a robust and broadly applicable strategy for identifying tumor markers to better inform the development of targeted cancer therapy. SIGNIFICANCE: Single-cell transcriptomic profiling and multiomic cross-validation to uncover therapeutic targets identifies 38 myeloma marker genes, including 11 transcribing surface proteins with previously uncharacterized potential for targeted antitumor therapy.


Asunto(s)
Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Multiómica , Proteómica , Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica/métodos
14.
Int J Biol Macromol ; 205: 385-395, 2022 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-35183600

RESUMEN

The current study explores the effect of the extracted novel Mushroom polysaccharides and its formulation onto Alginate (Alg.)/kappa carrageenan microcapsules to exert immunotherapeutic effect upon activating gut resident natural killer cells (NK) against colon cancer. The extracted polysaccharides of Agaricus bisporus MH751906 was microcapsulated in Alg/κ-carrageenan microcapsules as an oral delivery system for colon cancer. The microcapsule is characterized by SEM, FTIR, Raman and TGA; and showed a superior acidic stability, controlled release, and thermal stability at high temperature with higher hydrogel swelling rate in colon-mimicking pH. Upon activation of human NK cells with microcapsules (ANK cells), a significant increase in CD16+CD56+ NK cell populations were recorded. These activated NK cells showed 74.09% cytotoxic effects against human colon cancer Caco-2 cells where majority of cancer cell populations arrested at G0/G1 phase leading to apoptosis. The apoptotic molecular mechanism induced by ANK cells on Caco-2 treated cells is through down regulations of both BCL2 and TGF surviving genes and up regulation in IkappaB-α gene expression. Therefore, this novel polysaccharides-alginate/κ-carrageenan microcapsules can be used as an oral targeted delivery system for colon cancer immunotherapy.


Asunto(s)
Agaricus , Neoplasias del Colon , Agaricus/química , Alginatos/química , Células CACO-2 , Cápsulas , Carragenina/química , Neoplasias del Colon/tratamiento farmacológico , Humanos , Inmunoterapia , Células Asesinas Naturales , Polisacáridos/química
15.
ACS Appl Bio Mater ; 2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-36040424

RESUMEN

We synthesized a stable, eco-friendly, and low-cost polyaniline@ß-cyclodextrin (PANI@ß-CD) nanocomposite via oxidative polymerization for phenol adsorption from water waste since phenol pollution is a global danger to human and animal health and the environment. The production of the composite and synergistic alteration of PANI with ß-CD resulted in 66% reduction in particle size from 59 nm (PANI) to 20 nm (PANI@ß-CD) as well as better phenol adsorption. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscope (SEM), and thermogravimetric analysis (TGA) were used to analyze the produced PANI@ß-CD nanocomposite. Our results show the optimum conditions for phenol adsorption: time (50 min), pH (8.0), nanosorbent dose (0.5 g), and the sorption isotherm fitted with Langmuir model; the monolayer adsorption capacity of the prepared PANI@ß-CD for phenol was determined to be 8.56 mg g-1. The average pore size, total pore volume, and surface area of PANI/ßCD nanocomposite are 15.62 nm, 0.1586 cm3/g, and 90.901 m2/g, respectively, for the pseudo second order model. Finally, modifying PANI nanoparticles with ßCD allowed reusability up to four cycles with superior adsorption performance of ∼95% using (0.01 N) HNO3.

16.
ACS Omega ; 7(31): 27239-27248, 2022 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-35967052

RESUMEN

Water polluted by phenolic compounds is a global threat to health and the environment; accordingly, we prepared a green novel sorbent biological system from a chitosan (CS), gelatin (GT), and Chlorella vulgaris freshwater microalgae (m-Alg) composite impregnated with zinc oxide nanoparticles (ZnO-NPs) for the remediation of bisphenol-A (BPA) from water. C. vulgaris was selected to be one of the constituents of the prepared composite because of its high capability in phytoremediation. The morphology and the structure of CS/GT*m-Alg/ZnO beads were characterized by SEM, FTIR, XRD, and TGA. Different monitoring experimental conditions, such as contact time, pH, BPA concentration, and sorbent dosage, were optimized. The optimum conditions for the adsorption process showed outstanding removal efficiency toward BPA at pH 4.0, contact time 40.0 min, and 40.0 mg L-1 BPA initial concentration. Langmuir, Freundlich, and Temkin isotherm models have been studied for adsorption equilibrium, and the best fit is described by the Langmuir adsorption isotherm. The adsorption kinetics has been studied using pseudo-first-order (PFO), pseudo-second-order (PSO), Elovich, and intraparticle diffusion (IPD) models. The pseudo-second-order kinetic model shows the optimum experimental fit. The monolayer adsorption capacity of the prepared CS/GT*m-Alg/ZnO for BPA was determined to be 38.24 mg g-1. The prepared CS/GT*m-Alg/ZnO beads show advantageous properties, such as their high surface area, high adsorption capacity, reusability, and cost-effectiveness.

17.
Front Plant Sci ; 13: 997475, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36325574

RESUMEN

Soil pollution with cadmium (Cd) is a serious threat to plant growth and development. On the other hand, silicon (Si) can support plants to cope with Cd stress. However, the Cd stress mitigating impact of Si reduction in pea (Pisum sativum L.) is not known. The objective of this study is to see if and how Si can reduce Cd toxicity. To the end, a greenhouse pot experiment was performed twice during the 2018/2019 and 2019/2020 seasons to investigate the effect of Si on the growth, anatomy, and biochemistry of Cd stressed peas plants. Cd exposure increased the contents of Cd ions in the root and shoot of pea plants. Consequentially, Cd accumulation in pea tissue significantly reduced plant growth i.e., plant height, leaf area, and shoot and root dry weights. The effect of Cd was concentration-dependent, where at low concentration (50 mg/kg soil), the plant height was 94.33 and 97.33cm and at high concentration (100 mg/kg soil), it was 89.0 and 91.0 cm in the two seasons, respectively. This growth reduction can be explained by the decrease in plants' photosynthesis, whereas plants exposed to Cd toxicity had lower chlorophyll levels. At the anatomy level, high Cd concentrations resulted in anatomical abnormalities such as an unusual vascular system, abnormal lignification in the pith parenchyma, and enlarged cortical cells. Moreover, all Cd concentrations resulted in a highly significant decrease in stomatal area and stomatal density (the number of stomata per mm2). In addition to growth inhibition, Cd-induced oxidative damage to pea plants as indicated by increased hydrogen peroxide (H2O2) and Malondialdehyde (MDA) levels. To reduce stress toxicity, plants treated with Cd at 50 and 100 (mg/kg) showed a significant increase in antioxidant capacity. Peroxidase (POD) enzyme activity was significantly increased by 41.26%, 28.64%, 77.05%, and 60.77% in both seasons, respectively. Si at 300 ppm under Cd (100 mg/kg) stress conductions considerably reduced (MDA) contents by 29.02% and 29.12%, in the two seasons, respectively. The findings pointed out that Si's ability to protect pea against the oxidative stress caused by Cd toxicity.

18.
Front Plant Sci ; 13: 923872, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36061769

RESUMEN

Salinity is an abiotic stress that reduces the seed germination and productivity of wheat. The objective of this study was to assess the impact of irrigation with magnetically treated seawater on the germination, growth, certain physiological and anatomical parameters, and production attributes of wheat (Triticum aestivum L.) cv. Sakha 93 plants. Experiments were conducted in the Experimental Farm of the Faculty of Agriculture, Menoufia University, Egypt, during two consecutive winter seasons. Pot experiments involved ten treatments with non-magnetized and magnetized water with various degrees of salinity. Plant samples were taken 95 days after sowing. Irrigation with magnetically treated seawater was found to have beneficial effects on plant growth, water relations, biochemical characteristics, and yield components compared with untreated plants. The germination of wheat seeds increased 13% when treated with magnetic seawater. On the yield scale, the spike length was increased by 40% in season one, and 82% in season two when compared to the control, while the weight of 100 grains increased by 148% and 171%, in each season, respectively, when treated with magnetic water. The anatomical leaf and stem parameters of the plants were markedly improved by watering with magnetically treated seawater at 10 dS m-1 compared to the control. However, the leaf water deficit, transpiration rate, and abscisic acid content in the plant shoots decreased significantly (p < 0.05). The use of magnetically treated seawater of up to 7.5 dS m-1, instead of tap water, is recommended due to benefits to germination and seedling parameters, growth, yield, and physiological, chemical, and anatomical characteristics. In conclusion, magnetic treatment of seawater improved germination performance, growth, and yield of wheat under saline conditions.

19.
Sci Rep ; 12(1): 15227, 2022 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-36075945

RESUMEN

This work was carried out to select cotton genotypes adapted to semi-arid climate conditions cultivated under irrigation for high yields and the standards of the fiber quality properties required by the textile industry. Also to determine the predicted and realized gains from different selection indices to improve some economic characters under water stress conditions. Except for lint percentage and Pressley index, F4 generation reduced PCV and GCV values for all studied characters due to reduction in genetic variability and heterozygosity due to different selection procedures that exhausted a significant part of variability. Except for fiber length and micronaire reading, mean performance in the F4 generation was revealed to be higher than those in the F3 generation for all studied characters. However, micronaire reading was lower (desirable) in F4 than F3 generation. Generally, genotypic correlations were higher than phenotypic correlations. Direct selection for lint index (Ped.3) was the most efficient in improving lint cotton yield/plant and bolls/plant. However, the multiplicative index involving all studied characters (I.5) exhibited the highest values for boll weight. Also, the Ped.2 index (direct selection for lint percentage) proved to be the most efficient in improving seed and lint indexes. Direct selection for lint cotton yield/plant (Ped.1) could produce the highest desirable values for lint percentage and seed per boll with a relatively reasonable yield. A selection index involving yield and its components (I.3) is recommended in improving uniformity index, fiber strength, and micronaire reading. The superior five families released from these indices in F4 generation exceeded the better parent for lint cotton yield/plant, bolls/plant, boll weight, seeds/boll, lint index, and reasonable fiber traits. These families could be continued to further generations as breeding material for developing water deficit tolerant genotypes.


Asunto(s)
Deshidratación , Fitomejoramiento , Fibra de Algodón , Egipto , Genotipo , Gossypium/genética , Humanos , Fenotipo
20.
Front Plant Sci ; 13: 866742, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35873955

RESUMEN

Drought is considered a major threat to rice production. This study aimed to determine the effects of drought stress on the estimates of heterosis and the combining ability of rice genotypes for the number of days to 50% heading, plant height, number of panicles per plant, panicle length, number of filled grains per panicle, and grain yield per plant. Field experiments were conducted at the Rice Research and Training Center, Kafr El Sheikh, Egypt, during the rice-growing season in 2018 and 2019. Eight rice genotypes (Giza178, Giza179, Sakha106, Sakha107, Sakha108, WAB1573, NERICA4, and IET1444) were crossed in a half-diallel cross in the rice-growing season in 2018, which yielded a wide range of variability in numerous agronomic traits and drought tolerance measurements. In 2019, these parents and their 28 F1 crosses were produced by employing a three-replication randomized complete block design under normal and water stress conditions. The results showed remarkable differences across the studied genotypes under normal and water stress conditions. Under both conditions, Sakha107 was the best general combiner for earliness and short stature. Giza179 and Sakha108 were the best general combiners for grain yield per plant and one or more of its characteristics. Furthermore, in both normal and water stress conditions, Giza179 exhibited the highest general combining ability effects for all attributes that were evaluated. Under normal and water stress conditions, the Giza179 × Sakha107 cross demonstrated substantial and desirable specific combining ability effects on all the examined traits, which suggested that it could be considered for use in rice hybrid breeding programs. Therefore, we recommend that these vital indirect selection criteria to be considered for improving rice grain yield under drought conditions.

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