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1.
Chem Biol Interact ; 367: 110171, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36108716

RESUMO

Selenium is a trace element that has been shown to inhibit the growth of various cancer cell types. However, its role in cervical cancer and its underlying mechanisms remains largely unknown. Herein, we explored the anti-cervical cancer effect of selenium and its potential mechanisms through xenograft and in vitro experiments. HeLa cell xenografts in female nude mice showed tumor growth retardation, with no obvious liver and kidney toxicity, after being intraperitoneally injected with 3 mg/kg sodium selenite (SS) for 14 days. Compared to the control group, selenium levels in the tumor tissue increased significantly after SS treatment. In vitro experiments, SS inhibited the viability of HeLa and SiHa cells, blocked the cell cycle at the S phase, and enhanced apoptosis. RNA-sequencing, Kyoto encyclopedia of genes and genomes pathway analysis showed that forkhead box protein O (FOXO) was a key regulatory signaling pathway for SS to exhibit anticancer effects. Gene Ontology analysis filtered multiple terms associated with apoptosis, anti-proliferation, and cell cycle arrest. Further research revealed that SS increased intracellular reactive oxygen species (ROS) and impaired mitochondrial function, which activated adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) via phosphorylation at Thr172, resulting in activation of FOXO3a and its downstream growth arrest and DNA damage-inducible alpha (GADD45a). In summary, SS exhibited anti-cervical cancer effects, and their mechanisms may be that SS is involved in inducing cell cycle arrest and potentiating cell apoptosis caused by ROS-dependent activation of the AMPK/FOXO3a/GADD45a axis.


Assuntos
Selênio , Oligoelementos , Neoplasias do Colo do Útero , Proteínas Quinases Ativadas por AMP/metabolismo , Adenosina/farmacologia , Monofosfato de Adenosina/farmacologia , Animais , Apoptose , Proteínas de Ciclo Celular , Feminino , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Células HeLa , Humanos , Camundongos , Camundongos Nus , RNA , Espécies Reativas de Oxigênio/metabolismo , Selênio/farmacologia , Selenito de Sódio/farmacologia , Neoplasias do Colo do Útero/patologia
2.
J Trace Elem Med Biol ; 73: 127041, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35905604

RESUMO

BACKGROUND: The effect of selenoprotein P (SELENOP) levels on the sensitivity of cervical cancer patients to concurrent chemoradiotherapy (CCRT) has not been reported. In this study, the effects of the variations in plasma SELENOP levels on the sensitivity of cervical cancer patients to CCRT were investigated using metabonomics. METHODS: Two patient groups were evaluated, i.e., the case group: 11 patients with intermediate to advanced primary squamous cervical cancer, who developed resistance against CCRT, and the sensitivity group: 11 patients who did not develop resistance were matched in a 1:1 ratio (controls). Blood samples were collected before and after CCRT, and the plasma SELENOP levels were measured by ELISA. The different metabolites present in the plasma were analyzed by UPLC-MS-MS. RESULTS: SELENOP levels exhibited a significant reduction in both the resistant and sensitive groups after CCRT (F = 50.705, P < 0.001), and interaction effects between sensitivity and pre-and post-treatment on SELENOP levels were observed (F = 7.414, P = 0.013). Further, a more significant reduction in the SELENOP levels was observed in the CCRT-resistant group (mean reduction, 0.028 µg/mL; P < 0.001) than in the sensitive group (mean reduction, 0.013 µg/mL; P = 0.006). Four metabolic biomarkers, i.e., C18, C19, C20 sphingomyelin, and phosphatidylcholine 20:2/22:6, were shown to be differentially expressed between the resistant and sensitive groups pre-and post-treatment. C20 sphingomyelin levels exhibited a significant correlation with SELENOP levels (r = -0.326, P = 0.031). CONCLUSION: The levels of plasma SELENOP in the CCRT-resistant group decreased significantly, suggesting that SELENOP might affect the sensitivity by modulating lipid synthesis and metabolism.


Assuntos
Neoplasias do Colo do Útero , Quimiorradioterapia , Cromatografia Líquida , Feminino , Humanos , Estudos Retrospectivos , Selenoproteína P , Esfingomielinas , Espectrometria de Massas em Tandem , Neoplasias do Colo do Útero/tratamento farmacológico
3.
J Am Chem Soc ; 144(21): 9413-9420, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35587132

RESUMO

We describe the development of a general palladium-catalyzed carbonylative method to synthesize acyl fluorides from aryl, heteroaryl, alkyl, and functionalized organic halides. Mechanistic analysis suggests that the reaction proceeds via the synergistic combination of visible light photoexcitation of Pd(0) to induce oxidative addition with a ligand-favored reductive elimination. These together create a unidirectional catalytic cycle that is uninhibited by the classical effect of carbon monoxide coordination. Coupling the catalytic formation of acyl fluorides with their subsequent nucleophilic reactions has opened a method to perform carbonylation reactions with unprecedented breadth, including the assembly of highly functionalized carbonyl-containing products.


Assuntos
Fluoretos , Paládio , Catálise , Ligantes , Luz
4.
Gene ; 673: 225-238, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-29933020

RESUMO

The complete mitochondrial genome is greatly important for studies on genetic structure and phylogenetic relationship at various taxonomic levels. To obtain information about the evolutionary trends of mtDNA in the Ulvophyceae and also to gain insights into the phylogenetic relationships between ulvophytes and other chlorophytes, we determined the mtDNA sequence of Caulerpa lentillifera (sea grape) using de novo mitochondrial genome sequencing. The complete genomic DNA of C. lentillifera was circular and 209,034 bp in length, and it was the largest green-algal mitochondrial genome sequenced to date, with a low gene density of 65.2%, which is reminiscent of the "expanded" pattern of evolution exhibited by embryophyte mtDNAs. The C. lentillifera mtDNA consisted of a typical set of 17 protein-coding genes (PCGs), 20 transfer RNA (tRNA) genes, three ribosomal RNA (rRNA) genes, 42 putative open reading frames (ORFs) and 29 introns, which had homologs in green-algal mtDNAs displaying an "ancestral" or a "reduced-derived" pattern of evolution. The overall base composition of its mitochondrial genome was 24.19% for A, 24.94% for T, 25.80% for G, 25.07% for C and 50.87% for GC. The mitochondrial genome of C. lentillifera was characterized by numerous small intergenic regions and introns, which was clearly different from other green algae. With the exception of the NADH dehydrogenase subunit 6 (ND6), ND1, ATP and three tRNA genes (tRNA-His, tRNA-Thr and tRNA-Ala), all other mitochondrial genes were encoded on the heavy strand. All of the PCGs had ATG as their start codon and employed TAA, TGA or TAG as their termination codon. To gain insights into the evolutionary trends of mtDNA in the Ulvophyceae, we inferred the complete mtDNA sequence of C. lentillifera, an ulvophyte belonging to a distinct, early-diverging lineage. Taken together, our data offered useful information for the studies on phylogenetic hypotheses and phylogenetic relationships of C. lentillifera within the Chlorophyta.


Assuntos
Caulerpa/genética , DNA Mitocondrial/genética , Genoma Mitocondrial , DNA de Algas/genética , Evolução Molecular , Biblioteca Gênica , Genoma , Íntrons , Conformação de Ácido Nucleico , Fases de Leitura Aberta , Filogenia , RNA Ribossômico/genética , RNA de Transferência/genética
5.
J Vasc Interv Neurol ; 9(1): 60-5, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27403226

RESUMO

BACKGROUND AND PURPOSE: Data from electroencephalography (EEG) in preterm infants and neonates suggest that electroencephalographic abnormalities are likely present during antepartum period or fetal stage. We describe our initial effort to record fetal EEG with emphasis on technical aspects since such technique has not been developed as a viable and reproducible method. METHODS: The fetal heads were located in two pregnant volunteers (29 years old and 26 years old) with 28 weeks of gestation by ultrasound imaging. Four surface electrodes were placed on maternal abdominal surface approximately 5 cm anterior to the lateral aspect of fetal head as confirmed by acoustic shadowing of the electrodes on ultrasound. A second set of recordings were performed in first volunteer with four electrodes placed on the maternal abdominal surface in front of the uterus distant to fetal head. RESULTS: The analysis in the first volunteer demonstrated that the activity consisted of mixture of theta (4-7 Hz) and delta (1-4 Hz) waves which formed approximately 70% and 30% of the background rhythm. The analysis in the second volunteer demonstrated that the activity consisted of mixture of theta and delta, which formed approximately 30% and 70% of the background rhythm. There was superimposed beta (13-30 Hz) and infrequently gamma (30-100 Hz) activity. Maternal electrocardiographic QRS complex and respiratory artifacts were seen in some leads. During second recording, the electrodes distant to fetal head recorded predominantly delta with lesser proportion of theta waves. CONCLUSIONS: We report our initial experience in acquisition of fetal EEG. The findings reported here will help to guide further research into developing methodologies for the performance of fetal EEG.

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