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1.
Mol Ther ; 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38879755

RESUMEN

The extensive degeneration of functional somatic cells and the depletion of endogenous stem/progenitor populations present significant challenges to tissue regeneration in degenerative diseases. Currently, a cellular reprogramming approach enabling directly generating corresponding progenitor populations from degenerative somatic cells remains elusive. The present study focused on intervertebral disc degeneration (IVDD) and identified a three-factor combination (OCT4, FOXA2, TBXT [OFT]) that could induce the dedifferentiation-like reprogramming of degenerative nucleus pulposus cells (dNPCs) toward induced notochordal-like cells (iNCs). Single-cell transcriptomics dissected the transitions of cell identity during reprogramming. Further, OCT4 was found to directly interact with bromodomain PHD-finger transcription factor to remodel the chromatin during the early phases, which was crucial for initiating this dedifferentiation-like reprogramming. In rat models, intradiscal injection of adeno-associated virus carrying OFT generated iNCs from in situ dNPCs and reversed IVDD. These results collectively present a proof-of-concept for dedifferentiation-like reprogramming of degenerated somatic cells into corresponding progenitors through the development of a factor-based strategy, providing a promising approach for regeneration in degenerative disc diseases.

2.
Plant J ; 115(4): 937-951, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37154288

RESUMEN

Plant height (PH) is an important agronomic trait affecting crop architecture, biomass, resistance to lodging and mechanical harvesting. Elucidating the genetic governance of plant height is crucial because of the global demand for high crop yields. However, during the rapid growth period of plants the PH changes a lot on a daily basis, which makes it difficult to accurately phenotype the trait by hand on a large scale. In this study, an unmanned aerial vehicle (UAV)-based remote-sensing phenotyping platform was applied to obtain time-series PHs of 320 upland cotton accessions in three different field trials. The results showed that the PHs obtained from UAV images were significantly correlated with ground-based manual measurements, for three trials (R2 = 0.96, 0.95 and 0.96). Two genetic loci on chromosomes A01 and A11 associated with PH were identified by genome-wide association studies (GWAS). GhUBP15 and GhCUL1 were identified to influence PH in further analysis. We obtained a time series of PH values for three field conditions based on remote sensing with UAV. The key genes identified in this study are of great value for the breeding of ideal plant architecture in cotton.


Asunto(s)
Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Mapeo Cromosómico , Sitios de Carácter Cuantitativo/genética , Dispositivos Aéreos No Tripulados , Factores de Tiempo , Fitomejoramiento
3.
BMC Biol ; 21(1): 106, 2023 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-37173786

RESUMEN

BACKGROUND: Anthocyanins, a class of specialized metabolites that are ubiquitous among plant species, have attracted a great deal of attention from plant biologists due to their chemical diversity. They confer purple, pink, and blue colors that attract pollinators, protect plants from ultraviolet (UV) radiation, and scavenge reactive oxygen species (ROS) to facilitate plant survival during abiotic stress. In a previous study, we identified Beauty Mark (BM) in Gossypium barbadense as an activator of the anthocyanin biosynthesis pathway; this gene also directly led to the formation of a pollinator-attracting purple spot. RESULTS: Here, we found that a single nucleotide polymorphism (SNP) (C/T) within the BM coding sequence was responsible for variations in this trait. Transient expression assays of BM from G. barbadense and G. hirsutum in Nicotiana benthamiana using luciferase reporter gene also suggested that SNPs in the coding sequence could be responsible for the absent beauty mark phenotype observed in G. hirsutum. We next demonstrated that the beauty mark and UV floral patterns are associated phenotypes and that UV exposure resulted in increased ROS generation in floral tissues; BM thus contributed to ROS scavenging in G. barbadense and wild cotton plants with flowers containing the beauty mark. Furthermore, a nucleotide diversity analysis and Tajima's D Test suggested that there have been strong selective sweeps in the GhBM locus during G. hirsutum domestication. CONCLUSIONS: Taken together, these results suggest that cotton species differ in their approaches to absorbing or reflecting UV light and thus exhibit variations in floral anthocyanin biosynthesis to scavenge reactive ROS; furthermore, these traits are related to the geographic distribution of cotton species.


Asunto(s)
Antocianinas , Gossypium , Gossypium/genética , Antocianinas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Adaptación Fisiológica , Fenotipo
4.
Planta ; 257(3): 49, 2023 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-36752875

RESUMEN

MAIN CONCLUSION: Patatin-related phospholipase A genes were involved in the response of Gossypium hirsutum to drought and salt tolerance. pPLA (patatin-related phospholipase A) is a key enzyme that catalyzes the initial step of lipid hydrolysis, which is involved in biological processes, such as drought, salt stress, and freezing injury. However, a comprehensive analysis of the pPLA gene family in cotton, especially the role of pPLA in the response to drought and salt tolerance, has not been reported so far. A total of 33 pPLA genes were identified in this study using a genome-wide search approach, and phylogenetic analysis classified these genes into three groups. These genes are unevenly distributed on the 26 chromosomes of cotton, and most of them contain a few introns. The results of the collinear analysis showed that G. hirsutum contained 1-5 copies of each pPLA gene found in G. arboreum and G. raimondii. The subcellular localization analysis of Gh_D08G061200 showed that the protein was localized in the nucleus. In addition, analysis of published upland cotton transcriptome data revealed that six GhPLA genes were expressed in various tissues and organs. Two genes (Gh_A04G142100.1 and Gh_D04G181000.1) were highly expressed in all tissues under normal conditions, showing the expression characteristics of housekeeping genes. Under different drought and salt tolerance stresses, we detected four genes with different expression levels. This study helps to clarify the role of pPLA in the response to drought and salt tolerance.


Asunto(s)
Gossypium , Transcriptoma , Gossypium/metabolismo , Mapeo Cromosómico , Filogenia , Fosfolipasas/genética , Fosfolipasas/metabolismo , Regulación de la Expresión Génica de las Plantas , Estrés Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
5.
Plant Biotechnol J ; 20(7): 1274-1284, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35266277

RESUMEN

Hybrid crop varieties have been repeatedly demonstrated to produce significantly higher yields than their parental lines; however, the low efficiency and high cost of hybrid seed production has limited the broad exploitation of heterosis for cotton production. One option for increasing the yield of hybrid seed is to improve pollination efficiency by insect pollinators. Here, we report the molecular cloning and characterization of a semidominant gene, Beauty Mark (BM), which controls purple spot formation at the base of flower petals in the cultivated tetraploid cotton species Gossypium barbadense. BM encodes an R2R3 MYB113 transcription factor, and we demonstrate that GbBM directly targets the promoter of four flavonoid biosynthesis genes to positively regulate petal spot development. Introgression of a GbBM allele into G. hirsutum by marker-assisted selection restored petal spot formation, which significantly increased the frequency of honeybee visits in G. hirsutum. Moreover, field tests confirmed that cotton seed yield was significantly improved in a three-line hybrid production system that incorporated the GbBM allele. Our study thus provides a basis for the potentially broad application of this gene in improving the long-standing problem of low seed production in elite cotton hybrid lines.


Asunto(s)
Gossypium , Vigor Híbrido , Animales , Cruzamientos Genéticos , Gossypium/genética , Semillas/genética , Tetraploidía
6.
Physiol Plant ; 174(6): e13787, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36169590

RESUMEN

Plant adaptation to challenging environmental conditions around the world has made root growth and development an important research area for plant breeders and scientists. Targeted manipulation of root system architecture (RSA) to increase water and nutrient use efficiency can minimize the adverse effects of climate change on crop production. However, phenotyping of RSA is a major bottleneck since the roots are hidden in the soil. Recently the development of 2- and 3D root imaging techniques combined with the genome-wide association studies (GWASs) have opened up new research tools to identify the genetic basis of RSA. These approaches provide a comprehensive understanding of the RSA, by accelerating the identification and characterization of genes involved in root growth and development. This review summarizes the latest developments in phenotyping techniques and GWAS for RSA, which are used to map important genes regulating various aspects of RSA under varying environmental conditions. Furthermore, we discussed about the state-of-the-art image analysis tools integrated with various phenotyping platforms for investigating and quantifying root traits with the highest phenotypic plasticity in both artificial and natural environments which were used for large scale association mapping studies, leading to the identification of RSA phenotypes and their underlying genetics with the greatest potential for RSA improvement. In addition, challenges in root phenotyping and GWAS are also highlighted, along with future research directions employing machine learning and pan-genomics approaches.


Asunto(s)
Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Raíces de Plantas/genética , Fenotipo , Plantas/genética
7.
Eur Spine J ; 31(2): 442-447, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34677679

RESUMEN

PURPOSE: Metagenomic next-generation sequencing (mNGS) is a new approach to identify the infecting organism in infectious diseases. Our aim was to evaluate the accuracy of mNGS in determining the etiology of spinal infection. METHODS: In this retrospective study, patients who had a suspected spinal infection and underwent mNGS for diagnosis in our hospital were eligible for inclusion. Samples for mNGS, culture, and histopathological tests were collected surgically or with a CT-guided needle biopsy. Sensitivity and specificity were calculated for mNGS and culture test, using histopathological results as reference. RESULTS: A total of 31 mNGS tests in 30 cases were included. Twenty-six cases were classified as infected, and four cases were considered aseptic. mNGS achieved a specificity of 75.0% [95% confidence interval (CI), 21.9% to 98.7%], sensitivity was 70.3% (95% CI, 49.7% to 85.5%). mNGS was more sensitive than culture at 14.8% (95% CI, 4.9% to 34.6%, P < 0.0001). However, the specificities of mNGS and culture were statistically similar. CONCLUSION: We described here the power of mNGS in the etiological diagnosing of spinal infection. Our study opens the possibility for more extensive use of mNGS techniques in the identification of pathogens in patients with suspected spinal infection.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Biometría , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Metagenómica/métodos , Estudios Retrospectivos , Sensibilidad y Especificidad
8.
Int J Mol Sci ; 23(15)2022 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-35955501

RESUMEN

Protoplasts, which lack cell walls, are ideal research materials for genetic engineering. They are commonly employed in fusion (they can be used for more distant somatic cell fusion to obtain somatic hybrids), genetic transformation, plant regeneration, and other applications. Cotton is grown throughout the world and is the most economically important crop globally. It is therefore critical to study successful extraction and transformation efficiency of cotton protoplasts. In the present study, a cotton callus protoplast extraction method was tested to optimize the ratio of enzymes (cellulase, pectinase, macerozyme R-10, and hemicellulase) used in the procedure. The optimized ratio significantly increased the quantity and activity of protoplasts extracted. We showed that when enzyme concentrations of 1.5% cellulase and 1.5% pectinase, and either 1.5% or 0.5% macerozyme and 0.5% hemicellulase were used, one can obtain increasingly stable protoplasts. We successfully obtained fluorescent protoplasts by transiently expressing fluorescent proteins in the isolated protoplasts. The protoplasts were determined to be suitable for use in further experimental studies. We also studied the influence of plasmid concentration and transformation time on protoplast transformation efficiency. When the plasmid concentration reaches 16 µg and the transformation time is controlled within 12-16 h, the best transformation efficiency can be obtained. In summary, this study presents efficient extraction and transformation techniques for cotton protoplasts.


Asunto(s)
Celulasa , Protoplastos , Fusión Celular , Pared Celular , Celulasa/genética , Poligalacturonasa
9.
Planta ; 254(2): 42, 2021 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-34331139

RESUMEN

MAIN CONCLUSION: The elevation of transcript levels of GhDREB1B causes the accumulation of osmoregulants and mitigation of reactive oxygen species, which contributes to the enhanced resistance to chilling stress in AiSheng98 cotton. Low temperature is one of the key environmental stresses that impairs cotton growth and restricts fiber productivity. Dehydration responsive element binding (DREB) transcription factors play an important role in cold response in plants by modulating the transcription level of cold-responsive genes to protect the plants from low-temperature stress. Here, we showed that GhDREB1B, a copy number variant in the AiSheng98 (AS98) cotton mutant, significantly improved chilling tolerance in cotton seedlings, while silencing of GhDREB1B made transgenic cotton sensitive to chilling stress in AS98 cotton compared with control plants. Elevated GhDREB1B transcript level activated the expression of major cold-responsive genes. Genome-wide expression profiling by RNA sequencing revealed the upregulation of genes related to fatty acids, lipid proteins, osmoprotection, and anti-oxidative enzymes in AiSheng98. Excessive accumulation of malondialdehyde (MDA) and higher ion leakage rates occurred in wild-type LFH10 plants when compared to those of Aisheng98 during chilling stress, signifying lower chilling tolerance in the wild-type than in Aisheng98. Furthermore, the Aisheng98 mutant under chilling stress accumulated higher levels of free proline and soluble sugar than LFH10 accumulated. These results suggest that GhDREB1B is a positive regulator and its variant can alter the expression patterns of major low-temperature stress-related genes and enhance chilling tolerance in cotton.


Asunto(s)
Variaciones en el Número de Copia de ADN , Regulación de la Expresión Génica de las Plantas , Frío , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Estrés Fisiológico/genética , Factores de Transcripción/genética
10.
New Phytol ; 229(4): 2091-2103, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33129229

RESUMEN

Improving yield is a primary mission for cotton (Gossypium hirsutum) breeders; development of cultivars with suitable architecture for high planting density (HPDA) can increase yield per unit area. We characterized a natural cotton mutant, AiSheng98 (AS98), which exhibits shorter height, shorter branch length, and more acute branch angle than wild-type. A copy number variant at the HPDA locus on Chromosome D12 (HPDA-D12), encoding a dehydration-responsive element-binding (DREB) transcription factor, GhDREB1B, strongly affects plant architecture in the AS98 mutant. We found an association between a tandem duplication of a c. 13.5 kb segment in HPDA-D12 and elevated GhDREB1B expression resulting in the AS98 mutant phenotype. GhDREB1B overexpression confers a significant decrease in plant height and branch length, and reduced branch angle. Our results suggest that fine-tuning GhDREB1B expression may be a viable engineering strategy for modification of plant architecture favorable to high planting density in cotton.


Asunto(s)
Variaciones en el Número de Copia de ADN , Gossypium , Fibra de Algodón , Regulación de la Expresión Génica de las Plantas , Gossypium/genética , Fenotipo , Factores de Transcripción/genética
11.
Small ; 16(8): e1906415, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32003924

RESUMEN

Spinal cord injury (SCI) is a devastating disorder, leading to permanent motor and sensory deficit. Despite recent advances in neurosciences, the treatment efficacy on SCI patients remains unsatisfactory, mainly due to the poor accumulation, short retention, and lack of controlled release of therapeutics in lesion tissue. Herein, an injured spinal cord targeting prodrug polymer micelle is built. An esterase-responsive bond is used to link apocynin (APO) monomer, because of the enhanced esterase activity found in microglia cells after activation, which ensures a controlled degradation of APO prodrug (Allyloxypolyethyleneglycol-b-poly [2-(((4-acetyl-2-methoxyphenoxy)carbonyl)oxy)ethyl methacrylate], APEG-PAPO or PAPO) by activated microglia cells. A scar tissue-homing peptide (cysteine-alanine-glutamine-lysine, CAQK) is introduced to the PAPO to endow the polymer micelle the lesion tissue-targeting ability. As a result, this CAQK-modified prodrug micelle (cPAM) exhibits an improved accumulation and prolonged retention in lesion tissue compared to the control micelle. The cPAM also leads to superior tissue protection and sustained motor function recovery than the control groups in a mouse model of SCI. In conclusion, the cPAM induces an effective treatment of SCI by the lesion tissue specific delivery of the prodrug polymer via its robust scar binding effect, making the scar tissue a drug releasing platform for sustained treatment of SCI.


Asunto(s)
Cicatriz , Micelas , Polímeros , Traumatismos de la Médula Espinal , Animales , Ratones , Microglía/metabolismo , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/química , Polímeros/química , Traumatismos de la Médula Espinal/tratamiento farmacológico
12.
Cytotherapy ; 22(4): 193-203, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32173261

RESUMEN

Spinal cord injury (SCI) is a common disease and a major cause of paralysis, carrying much burden around the world. Despite the progress made with growth factors therapy, the response rate of acute SCI treatment still remains unsatisfactory, due largely to complex and severe inflammatory reactions. Herein, we prepare a MFG-E8-loaded copolymer system-based anti-inflammation therapy for SCI treatment. It is shown that the MFG-E8-loaded copolymer system can decrease pro-inflammatory cytokine expression and neuron death. In a rat model of crush-caused SCI, the copolymer system shows significant therapeutic efficacy by ameliorating inflammation, decreasing fibrotic scar, promoting myelin regeneration and suppressing overall SCI severity.


Asunto(s)
Antígenos de Superficie/administración & dosificación , Muerte Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Proteínas de la Leche/administración & dosificación , Vaina de Mielina/metabolismo , FN-kappa B/metabolismo , Polietilenglicoles/administración & dosificación , Poliglactina 910/administración & dosificación , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Hidrogeles/administración & dosificación , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inyecciones , Regeneración Nerviosa/efectos de los fármacos , Células PC12 , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Resultado del Tratamiento
13.
Int J Mol Sci ; 21(18)2020 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-32899571

RESUMEN

Allotetraploid cotton (Gossypium hirsutum and Gossypium barbadense) are cultivated worldwide for its white fiber. For centuries, conventional breeding approaches increase cotton yield at the cost of extensive erosion of natural genetic variability. Sea Island cotton (G. barbadense) is known for its superior fiber quality, but show poor adaptability as compared to Upland cotton. Here, in this study, we use ethylmethanesulfonate (EMS) as a mutagenic agent to induce genome-wide point mutations to improve the current germplasm resources of Sea Island cotton and develop diverse breeding lines with improved adaptability and excellent economic traits. We determined the optimal EMS experimental procedure suitable for construction of cotton mutant library. At M6 generation, mutant library comprised of lines with distinguished phenotypes of the plant architecture, leaf, flower, boll, and fiber. Genome-wide analysis of SNP distribution and density in yellow leaf mutant reflected the better quality of mutant library. Reduced photosynthetic efficiency and transmission electron microscopy of yellow leaf mutants revealed the effect of induced mutations at physiological and cellular level. Our mutant collection will serve as the valuable resource for basic research on cotton functional genomics, as well as cotton breeding.


Asunto(s)
Biblioteca de Genes , Gossypium/genética , Semillas/genética , Mapeo Cromosómico/métodos , Cromosomas de las Plantas/genética , Metanosulfonato de Etilo/efectos adversos , Variación Genética/genética , Genoma de Planta/genética , Fenotipo , Fitomejoramiento/métodos , Sitios de Carácter Cuantitativo/genética
14.
Cancer Cell Int ; 19: 195, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31372095

RESUMEN

BACKGROUND: AZD7762 is a checkpoint kinase 1 (Chk 1) inhibitor, which has been reported to sensitize many tumor cells to DNA damage. However, whether AZD7762 could sensitize osteosarcoma cells to chemotherapy cisplatin has not been defined. METHODS: We used a variety of methods such as cell viability assays, flow cytometry, western blotting, and immunohistochemistry analysis to determine AZD7762 enhancing cisplatin-induced apoptosis on osteosarcoma cell lines in vitro and in vivo. RESULTS: In the present study, we demonstrated that AZD7762 could enhance cisplatin-mediated apoptosis and mitotic catastrophe of osteosarcoma cells in vitro, and promote the inhibition of xenograft growth induced by cisplatin in vivo. The mechanistic study indicated that AZD7762 enhance the effect of cisplatin through abrogating cisplatin-mediated G2/M arrest and inhibiting the cisplatin damage repair as demonstrated by increasing cisplatin-induced γH2AX expression. CONCLUSION: These results suggest that AZD7762 could effectively promote cisplatin-induced apoptosis and mitotic catastrophe in osteosarcoma cells. The clinical application of AZD7762 as an adjuvant in the chemotherapy of osteosarcoma should be further explored.

15.
FASEB J ; : fj201800373R, 2018 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-29890089

RESUMEN

Adipose tissue-derived stem cell (ADSC)-based therapy is promising for the treatment of intervertebral disc (IVD) degeneration, but the difficulty in inducing nucleus pulposus (NP)-like differentiation limits its clinical applications. Forkhead box (Fox)-A2 is an essential transcription factor for the formation of a normal NP. We demonstrated that type II collagen stimulates NP-like differentiation of ADSCs, partly by increasing the expression of FoxA2. We constructed FoxA2-overexpressing and -knockdown ADSCs by using lentiviral vectors. FoxA2 overexpression significantly enhanced NP-specific gene expression and the synthesis of glycosaminoglycan and collagen, whereas FoxA2 knockdown decreased NP-like differentiation and the expression of aggrecan and collagen II. The enhanced NP-like differentiation related to FoxA2 overexpression was partially rescued by an Shh signaling pathway inhibitor. In addition, FoxA2 inhibited the expression of Itg-α2 and further promoted NP-like differentiation induced by type II collagen. Furthermore, FoxA2-overexpressing ADSCs combined with type II collagen hydrogels promoted regeneration of degenerated NP in vivo. Our findings suggest that FoxA2 plays an essential role in the NP-like differentiation of ADSCs by activating the Shh signaling pathway.-Zhou, X., Ma, C., Hu, B., Tao, Y., Wang, J., Huang, X., Zhao, T., Han, B., Li, H., Liang, C., Chen, Q., Li, F. FoxA2 regulates the type II collagen-induced nucleus pulposus-like differentiation of adipose-derived stem cells by activation of the Shh signaling pathway.

16.
Med Sci Monit ; 24: 6742-6749, 2018 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-30248086

RESUMEN

BACKGROUND Cantharidin (CTD) is one of the major active ingredients of blister beetles and has significant antitumor activity in many cancer cell lines. The aim of our study was to evaluate the effect of CTD on the apoptosis of human osteosarcoma cells MG-63 and MNNG/HOS, and to explore the possible molecular mechanism. MATERIAL AND METHODS Osteosarcoma cells MG-63 and MNNG/HOS were treated with varying concentrations of CTD. The proliferation inhibition of cells was detected by MTS. Flow cytometry and Hoechst 33258 staining were used to determine cell cycle arrest and apoptosis, and apoptosis-related protein levels were analyzed by Western blotting. RESULTS Our current findings suggest that CTD could inhibit the proliferation of these 2 osteosarcoma cells. The cells treated with CTD showed an obvious apoptotic morphology, and CTD promoted cells apoptosis in a dose-dependent manner. In addition, cantharidin-induced apoptosis was accompanied by increased expression of Bax and PARP and decreased expression of Bcl-2, p-Akt, and p-Cdc2. CONCLUSIONS CTD accelerates the apoptosis of MG-63 and MNNG/HOS cells in a concentration-dependent manner through the mitochondria-dependent pathway, suggesting that use of CTD is a novel approach for the treatment of osteosarcoma.


Asunto(s)
Cantaridina/farmacología , Mitocondrias/efectos de los fármacos , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Osteosarcoma/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-bcl-2/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
17.
Nanomedicine ; 14(4): 1099-1110, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29462663

RESUMEN

Zinc phthalocyanine (ZnPc) is a highly potent second-generation photosensitizer for cancer photodynamic therapy (PDT) with attractive photo-physical and photo-chemical properties. However, poor solubility and strong trend of crystallization prevent it from loading in most of drug delivery systems and hamper its further application. Herein, to overcome this problem, an amphiphilic block copolymer poly(ethylene glycol)-poly[2-(methylacryloyl)ethylnicotinate] (PEG-PMAN) with aromatic nicotinate is used to load ZnPc for their π-π interactions. The formed PEG-PMAN/ZnPc nanoparticle (PPZ) dramatically increases reactive oxygen species production in osteosarcoma cells after light irradiation, causes mitochondrial injury and promotes cell cycle arrest at G2/M, leading to a 100-fold cytotoxicity improvement comparing with free ZnPc. The excellent therapeutic effectiveness and safety of PPZ are also proved by in vivo experiments operating on osteosarcoma model. The finding above indicates that PPZ has promising clinical applications as a next-generation photosensitizer in PDT of osteosarcoma.


Asunto(s)
Indoles/química , Compuestos Organometálicos/química , Osteosarcoma/terapia , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/química , Polímeros/química , Animales , Línea Celular Tumoral , Humanos , Isoindoles , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Micelas , Nanopartículas/química , Compuestos de Zinc
18.
Proc Natl Acad Sci U S A ; 112(35): 11102-7, 2015 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-26283354

RESUMEN

Grain size is one of the key factors determining grain yield. However, it remains largely unknown how grain size is regulated by developmental signals. Here, we report the identification and characterization of a dominant mutant big grain1 (Bg1-D) that shows an extra-large grain phenotype from our rice T-DNA insertion population. Overexpression of BG1 leads to significantly increased grain size, and the severe lines exhibit obviously perturbed gravitropism. In addition, the mutant has increased sensitivities to both auxin and N-1-naphthylphthalamic acid, an auxin transport inhibitor, whereas knockdown of BG1 results in decreased sensitivities and smaller grains. Moreover, BG1 is specifically induced by auxin treatment, preferentially expresses in the vascular tissue of culms and young panicles, and encodes a novel membrane-localized protein, strongly suggesting its role in regulating auxin transport. Consistent with this finding, the mutant has increased auxin basipetal transport and altered auxin distribution, whereas the knockdown plants have decreased auxin transport. Manipulation of BG1 in both rice and Arabidopsis can enhance plant biomass, seed weight, and yield. Taking these data together, we identify a novel positive regulator of auxin response and transport in a crop plant and demonstrate its role in regulating grain size, thus illuminating a new strategy to improve plant productivity.


Asunto(s)
Ácidos Indolacéticos/metabolismo , Oryza/metabolismo , Proteínas de Plantas/genética , Transporte Biológico , Biomasa , Oryza/genética
19.
BMC Bioinformatics ; 18(1): 482, 2017 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-29137598

RESUMEN

BACKGROUND: The traditional method of visualizing gene annotation data in JBrowse is converting GFF3 files to JSON format, which is time-consuming. The latest version of JBrowse supports rendering sorted GFF3 files indexed by tabix, a novel strategy that is more convenient than the original conversion process. However, current tools available for GFF3 file sorting have some limitations and their sorting results would lead to erroneous rendering in JBrowse. RESULTS: We developed GFF3sort, a script to sort GFF3 files for tabix indexing. Specifically designed for JBrowse rendering, GFF3sort can properly deal with the order of features that have the same chromosome and start position, either by remembering their original orders or by conducting parent-child topology sorting. Based on our test datasets from seven species, GFF3sort produced accurate sorting results with acceptable efficiency compared with currently available tools. CONCLUSIONS: GFF3sort is a novel tool to sort GFF3 files for tabix indexing. We anticipate that GFF3sort will be useful to help with genome annotation data processing and visualization.


Asunto(s)
Anotación de Secuencia Molecular/métodos , Programas Informáticos , Animales , Genómica/métodos , Humanos
20.
BMC Plant Biol ; 17(1): 101, 2017 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-28595571

RESUMEN

BACKGROUND: Cotton (Gossypium spp.) is the most important fiber and oil crop in the world. With the emergence of huge -omics data sets, it is essential to have an integrated functional genomics database that allows worldwide users to quickly and easily fetch and visualize genomic information. Currently available cotton-related databases have some weakness in integrating multiple kinds of -omics data from multiple Gossypium species. Therefore, it is necessary to establish an integrated functional genomics database for cotton. DESCRIPTION: We developed CottonFGD (Cotton Functional Genomic Database, https://cottonfgd.org ), an integrated database that includes genomic sequences, gene structural and functional annotations, genetic marker data, transcriptome data, and population genome resequencing data for all four of the sequenced Gossypium species. It consists of three interconnected modules: search, profile, and analysis. These modules make CottonFGD enable both single gene review and batch analysis with multiple kinds of -omics data and multiple species. CottonFGD also includes additional pages for data statistics, bulk data download, and a detailed user manual. CONCLUSION: Equipped with specialized functional modules and modernized visualization tools, and populated with multiple kinds of -omics data, CottonFGD provides a quick and easy-to-use data analysis platform for cotton researchers worldwide.


Asunto(s)
Bases de Datos Genéticas , Gossypium/genética , Predicción , Marcadores Genéticos , Variación Genética , Genoma de Planta , Almacenamiento y Recuperación de la Información , Internet , Anotación de Secuencia Molecular
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