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1.
J Reprod Immunol ; 164: 104273, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38852489

RESUMEN

Preeclampsia (PE) significantly contributes to obstetric complications and maternal mortality, yet its pathogenesis and mechanisms are not well understood. Sulfiredoxin-1 (SRXN1) is known for its antioxidant activity and its role in defending against oxidative stress; it is also linked to various cancers. However, the role of SRXN1 in PE remains unclear. Our study found a significant decrease in SRXN1 levels in the serum and placental tissues of patients with early-onset preeclampsia (EOPE). Similarly, a PE-like mouse model showed reduced SRXN1 expression. Our in vitro experiments showed that reducing SRXN1 impaired trophoblast viability, decreased invasion and migration, and led to cell death, primarily through ferroptosis. These results are consistent with analyses of placental tissues from EOPE patients. In summary, lower SRXN1 levels during pregnancy contribute to trophoblast ferroptosis, potentially affecting the development and progression of EOPE.


Asunto(s)
Ferroptosis , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro , Preeclampsia , Trofoblastos , Preeclampsia/inmunología , Preeclampsia/patología , Preeclampsia/metabolismo , Ferroptosis/inmunología , Femenino , Embarazo , Trofoblastos/metabolismo , Trofoblastos/patología , Humanos , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/metabolismo , Animales , Ratones , Placenta/metabolismo , Placenta/patología , Placenta/inmunología , Adulto , Modelos Animales de Enfermedad
2.
ACS Synth Biol ; 13(3): 816-824, 2024 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-38365187

RESUMEN

Candida glycerinogenes is an industrial yeast with excellent multistress resistance. However, due to the diploid genome and the lack of meiosis and screening markers, its molecular genetic operation is limited. Here, a gene editing system using the toxin-antitoxin pair relBE from the type II toxin-antitoxin system in Escherichia coli as a screening marker was constructed. The RelBE complex can specifically and effectively regulate cell growth and arrest through a conditionally controlled toxin RelE switch, thereby achieving the selection of positive recombinants. The constructed editing system achieved precise gene deletion, replacement, insertion, and gene episomal expression in C. glycerinogenes. Compared with the traditional amino acid deficiency complementation editing system, this editing system produced higher biomass and the gene deletion efficiency was increased by 3.5 times. Using this system, the production of 2-phenylethanol by C. glycerinogenes was increased by 11.5-13.5% through metabolic engineering and tolerance engineering strategies. These results suggest that the stable gene editing system based on toxin-antitoxin pairs can be used for gene editing of C. glycerinogenes to modify metabolic pathways and promote industrial applications. Therefore, the constructed gene editing system is expected to provide a promising strategy for polyploid industrial microorganisms lacking gene manipulation methods.


Asunto(s)
Antitoxinas , Toxinas Bacterianas , Alcohol Feniletílico , Pichia , Edición Génica/métodos , Antitoxinas/genética , Toxinas Bacterianas/genética , Escherichia coli/genética , Escherichia coli/metabolismo
3.
Org Lett ; 23(21): 8183-8188, 2021 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-34664959

RESUMEN

A nickel-catalyzed reductive cross coupling with phosphonium salts and allylic C(sp3)-O bond electrophiles, which granted direct construction of the C(sp2)-C(sp3) bond, is successfully developed. The protocol features broad substrate scope, high-functional-group tolerance, and heterocycle compatibility. Notably, the much more challenging reductive cross coupling with heterocyclic thiazolylphosphonium salts has also been accomplished for the first time.

4.
Materials (Basel) ; 13(7)2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32244790

RESUMEN

Hindered amine light stabilizers (HALSs) and nano ZnO were used to stabilize polypropylene (PP) film-based formulations that were exposed to ultraviolet (UV) light for different lengths of time, simulating the harsh outdoor weather of Dallas, Texas, USA. UV doses applied in our laboratory are 121 times larger than the UV dose provided by the sunlight in Texas. 15 different compositions were studied. Tensile behavior, UV transmittance, thermal stability (by thermogravimetric analysis) and dynamic friction of the so exposed PP-based films were determined. Scanning electron micrographs of fracture surfaces were obtained. Nano-ZnO-containing stabilizers impart strong UV resistance to our films. The combination of HALSs and nano-ZnO stabilizers makes the PP films harder-which is important for some PP applications, such as toy manufacturing.

5.
Appl Microbiol Biotechnol ; 104(9): 4093-4107, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32162090

RESUMEN

2-Phenylethanol (2-PE) is an important flavor compound but also impairs cell growth severely, which in turn blocks its bioproduction. However, the molecular mechanism of 2-PE tolerance is unclear. In this study, a superb 2-PE stress-tolerant and producing yeast, Candida glycerinogenes, was selected to uncover the underlying mechanism of 2-PE tolerance. We discovered that Hap5 is an essential regulator to 2-PE resistance, and its induction by 2-PE stress occurs at the post-transcriptional level, rather than at the transcriptional level. Under 2-PE stress, Hap5 is activated and imported into the nucleus rapidly. Then, the nuclear Hap5 binds to the glutathione synthetase (gsh2) promoter via CCAAT box, to induce the expression of gsh2 gene. The increased gsh2 expression contributes to enhanced cellular glutathione content, and consequently alleviates ROS accumulation, lipid peroxidation, and cell membrane damage caused by 2-PE toxicity. Specifically, increasing the expression of gsh2 is effective in improving not just 2-PE tolerance (33.7% higher biomass under 29 mM 2-PE), but also 2-PE production (16.2% higher). This study extends our knowledge of 2-PE tolerance mechanism and also provides a promising strategy to improve 2-PE production.


Asunto(s)
Proteínas Fúngicas/genética , Glutatión Sintasa/genética , Alcohol Feniletílico/farmacología , Pichia/efectos de los fármacos , Factores de Transcripción/genética , Membrana Celular/efectos de los fármacos , Regulación Fúngica de la Expresión Génica , Glutatión/metabolismo , Peroxidación de Lípido , Pichia/genética , Pichia/metabolismo , Regiones Promotoras Genéticas , Especies Reactivas de Oxígeno/metabolismo
6.
Biochem Biophys Res Commun ; 445(1): 175-9, 2014 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-24495805

RESUMEN

Gastric cancer (GC) is the second common cause of cancer-related death worldwide. microRNAs (miRNAs) play important roles in the carcinogenesis of GC. Here, we found that miR-22 was significantly decreased in GC tissue samples and cell lines. Ectopic overexpression of miR-22 remarkably suppressed cell proliferation and colony formation of GC cells. Moreover, overexpression of miR-22 significantly suppressed migration and invasion of GC cells. CD151 was found to be a target of miR-22. Furthermore, overexpression of CD151 significantly attenuated the tumor suppressive effect of miR-22. Taken together, miR-22 might suppress GC cells growth and motility partially by inhibiting CD151.


Asunto(s)
Movimiento Celular/genética , Proliferación Celular , MicroARNs/genética , Neoplasias Gástricas/genética , Tetraspanina 24/genética , Regiones no Traducidas 3'/genética , Secuencia de Bases , Western Blotting , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/genética , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , MicroARNs/metabolismo , Mutación , Invasividad Neoplásica , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Ácido Nucleico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Tetraspanina 24/metabolismo , Transfección
7.
Appl Microbiol Biotechnol ; 97(21): 9419-27, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23494619

RESUMEN

Self-assembling amphipathic peptides (SAPs) are a category of peptides that have unique sequences with alternating hydrophobic and hydrophilic residues that can spontaneously assemble into ordered nanostructures. In this study, we investigated the potential of fusion technique with SAPs to improve the thermal stability of lipoxygenase (LOX) from Pseudomonas aeruginosa. Six SAPs were individually fused to the N terminus of the LOX that resulted to the SAP-LOX fusions with approximately 2.3- to 4.5-fold enhanced thermal stability at 50 °C. The specific activities of the SAP-LOX fusions were also increased by 1.0- to 2.8-fold as compared with the wild-type LOX. This is the first report on the improvement of the thermal stability and specific activity of an enzyme by the fused SAPs, suggesting a simple technique to improve the catalytic properties of the recombinant enzymes by fusion expression.


Asunto(s)
Lipooxigenasa/química , Lipooxigenasa/metabolismo , Péptidos/metabolismo , Pseudomonas aeruginosa/enzimología , Estabilidad de Enzimas , Lipooxigenasa/genética , Péptidos/genética , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Temperatura
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