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1.
J Org Chem ; 89(9): 6169-6179, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38654590

RESUMEN

An efficient 2,2,6,6-tetramethylpiperidinooxy (TEMPO)-mediated hydroxyfluoroalkylation of arylamines with polyfluorinated alcohols via a radical-triggered C(sp2)-H/C(sp3)-H dehydrogenative cross-coupling process was developed. This transformation features simple operation, high atom economy, broad substrate compatibility, and excellent regioselectivity, leading to a series of hydroxyfluoroalkylated arylamine derivatives. Importantly, these synthetic products were further used to evaluate the antitumor activity in cancer cell lines by Cell Counting Kit-8 assay and the outcomes indicated that some compounds show a potent antiproliferative effect.

2.
J Med Genet ; 60(10): 933-938, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37012053

RESUMEN

BACKGROUND: Low-pass genome sequencing (LP GS) is an alternative to chromosomal microarray analysis (CMA). However, validations of LP GS as a prenatal diagnostic test for amniotic fluid are rare. Moreover, sequencing depth of LP GS in prenatal diagnosis has not been evaluated. OBJECTIVE: The diagnostic performance of LP GS was compared with CMA using 375 amniotic fluid samples. Then, sequencing depth was evaluated by downsampling. RESULTS: CMA and LP GS had the same diagnostic yield (8.3%, 31/375). LP GS showed all copy number variations (CNVs) detected by CMA and six additional variant of uncertain significance CNVs (>100 kb) in samples with negative CMA results; CNV size influenced LP GS detection sensitivity. CNV detection was greatly influenced by sequencing depth when the CNV size was small or the CNV was located in the azoospermia factor c (AZFc) region of the Y chromosome. Large CNVs were less affected by sequencing depth and more stably detected. There were 155 CNVs detected by LP GS with at least a 50% reciprocal overlap with CNVs detected by CMA. With 25 M uniquely aligned high-quality reads (UAHRs), the detection sensitivity for the 155 CNVs was 99.14%. LP GS using samples with 25 M UAHRs showed the same performance as LP GS using total UAHRs. Considering the detection sensitivity, cost and interpretation workload, 25 M UAHRs are optimal for detecting most aneuploidies and microdeletions/microduplications. CONCLUSION: LP GS is a promising, robust alternative to CMA in clinical settings. A total of 25 M UAHRs are sufficient for detecting aneuploidies and most microdeletions/microduplications.


Asunto(s)
Líquido Amniótico , Variaciones en el Número de Copia de ADN , Embarazo , Femenino , Humanos , Variaciones en el Número de Copia de ADN/genética , Diagnóstico Prenatal/métodos , Aneuploidia , Análisis por Micromatrices
3.
Lab Invest ; 103(4): 100043, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36870287

RESUMEN

Amplification biases caused by next-generation sequencing (NGS) for noninvasive prenatal screening (NIPS) may be reduced using single-molecule sequencing (SMS), during which PCR is omitted. Therefore, the performance of SMS-based NIPS was evaluated. We used SMS-based NIPS to screen for common fetal aneuploidies in 477 pregnant women. The sensitivity, specificity, positive predictive value, and negative predictive value were estimated. The GC-induced bias was compared between the SMS- and NGS-based NIPS methods. Notably, a sensitivity of 100% was achieved for fetal trisomy 13 (T13), trisomy 18 (T18), and trisomy 21 (T21). The positive predictive value was 46.15% for T13, 96.77% for T18, and 99.07% for T21. The overall specificity was 100% (334/334). Compared with NGS, SMS (without PCR) had less GC bias, a better distinction between T21 or T18 and euploidies, and better diagnostic performance. Overall, our results suggest that SMS improves the performance of NIPS for common fetal aneuploidies by reducing the GC bias introduced during library preparation and sequencing.


Asunto(s)
Síndrome de Down , Pruebas Prenatales no Invasivas , Embarazo , Femenino , Humanos , Aneuploidia , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Valor Predictivo de las Pruebas , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(12): 1484-1488, 2023 Dec 10.
Artículo en Zh | MEDLINE | ID: mdl-37994128

RESUMEN

OBJECTIVE: To explore the genetic basis for three fetuses with duodenal atresia or stenosis detected by ultrasonography. METHODS: Clinical data of three fetuses identified at the Women's Hospital Affiliated to Zhejiang University School of Medicine between January 2021 and August 2022 were collected. Umbilical cord blood and amniotic fluid samples of the fetuses and peripheral blood samples of their parents were collected and subjected to G-banded chromosomal karyotyping and single nucleotide polymorphism array (SNP array) analysis. RESULTS: Prenatal ultrasound of the three fetuses revealed duodenal atresia or stenosis. No karyotypic abnormality was detected, whilst SNP array has identified 1.4 ~ 1.9 Mb duplications at 17q12 in all of them, which were all predicted to be pathogenic copy number variations (CNVs). CONCLUSION: The 17q12 duplications probably underlay the duodenal atresia and stenosis in these fetuses, and chromosomal CNVs should be considered in duodenal atresia and stenosis.


Asunto(s)
Variaciones en el Número de Copia de ADN , Diagnóstico Prenatal , Embarazo , Humanos , Femenino , Constricción Patológica , Feto/diagnóstico por imagen , Aberraciones Cromosómicas
5.
BMC Genomics ; 23(Suppl 1): 559, 2022 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-35931959

RESUMEN

BACKGROUND: Plants synthesize metabolites to adapt to a continuously changing environment. Metabolite biosynthesis often occurs in response to the tissue-specific combinatorial developmental cues that are transcriptionally regulated. Polyphyllins are the major bioactive components in Paris species that demonstrate hemostatic, anti-inflammatory and antitumor effects and have considerable market demands. However, the mechanisms underlying polyphyllin biosynthesis and regulation during plant development have not been fully elucidated. RESULTS: Tissue samples of P. polyphylla var. yunnanensis during the four dominant developmental stages were collected and investigated using high-performance liquid chromatography and RNA sequencing. Polyphyllin concentrations in the different tissues were found to be highly dynamic across developmental stages. Specifically, decreasing trends in polyphyllin concentration were observed in the aerial vegetative tissues, whereas an increasing trend was observed in the rhizomes. Consistent with the aforementioned polyphyllin concentration trends, different patterns of spatiotemporal gene expression in the vegetative tissues were found to be closely related with polyphyllin biosynthesis. Additionally, molecular dissection of the pathway components revealed 137 candidate genes involved in the upstream pathway of polyphyllin backbone biosynthesis. Furthermore, gene co-expression network analysis revealed 74 transcription factor genes and one transporter gene associated with polyphyllin biosynthesis and allocation. CONCLUSIONS: Our findings outline the framework for understanding the biosynthesis and accumulation of polyphyllins during plant development and contribute to future research in elucidating the molecular mechanism underlying polyphyllin regulation and accumulation in P. polyphylla.


Asunto(s)
Liliaceae , Saponinas , Cromatografía Líquida de Alta Presión , Liliaceae/genética , RNA-Seq , Rizoma , Saponinas/química
6.
Zhongguo Zhong Yao Za Zhi ; 47(13): 3609-3618, 2022 Jul.
Artículo en Zh | MEDLINE | ID: mdl-35850815

RESUMEN

This study aims to systematically elucidate the pharmacodynamics and network pharmacological mechanism of Mongolian medicinal plants Scabiosa comosa, explore their key targets and related pathways, and further clarify the mechanism of the plants in treating liver fibrosis. Wistar rats were assigned into the blank group, carbon tetrachloride-induced liver fibrosis model group, and low-, medium-, and high-dose S. comosa groups. HE staining and Masson staining were performed for the observation of liver tissue under a microscope. Further, Wistar rats were assigned into a control group and a S. comosa group for administration. Seven days later, blood was collected from the abdominal aorta, and different doses of drug-containing serum samples were used to treat hepatic stellate cell-T6(HSC-T6). Flow cytometry was adopted to detect the apoptosis of HSC-T6 cells. Ultra-high performance liquid chromatography-time of flight-mass spectrometry(UHPLC-TOF-MS) was employed to determine the components in Scabiosa comosa. The target of S. comosa and liver fibrosis were obtained from SwissTargetPrediction and GeneCards, respectively, and the common targets were selected as the anti-liver fibrosis targets. Protein-protein interaction was analyzed via STRING. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were carried out via Metascape. Phosphatidylinosital 3-kinase(PI3 K), protein kinase B(AKT), p-AKT, p38, and p-p38 targets which are involved in the top-ranked PI3 K/AKT and mitogen activated kinase-like protein(MAPK) signaling pathways were selected for validation via Western blot. The HE and Masson staining results showed that Scabiosa alleviated the hyperplasia of connective tissue and the fibrosis. The serum containing Scabiosa significantly promoted the apoptosis of HSC-T6 in a concentration-dependent manner. A total of 76 chemical components were identified by UHPLC-TOF-MS, among which flavonoids, alkaloids, terpenoids, phenols, and fatty acids were the main components. According to the prediction, there were 63 anti-liver fibrosis targets in Scabiosa comosa, the annotated GO terms of which involved biological processes, cell components, and molecular functions. The KEGG pathway enrichment showed that the targets were mainly involved in PI3 K/AKT, epidermal growth factor receptor(EGFR), RAS-associated protein 1(Rap1), hypoxia-inducible factor 1(HIF-1), resistance to audiogenic seizures(Ras), and MAPK signaling pathways. Western blot results showed that compared with the model group, S. comosa down-regulated the protein levels of α-smooth muscle actin(α-SMA), collagen Ⅰ, PI3 K, AKT, p-AKT, p38, and p-p38 in liver tissue. Compared with the control group, the low-, medium-, and high-dose S. comosa significantly down-regulated the protein levels of α-SMA, collagen Ⅰ, PI3 K, AKT, p-AKT, p38, and p-p38 in HSC-T6. The evidence of pharmacodynamics, network pharmacology, and molecular biology indicated that the plants of S. comosa had significant activity against liver fibrosis, the mechanism of which may involve the regulation of the key targets PI3 K, AKT, and MAPK14 p38 in the PI3 K/AKT and MAPK signaling pathways.


Asunto(s)
Dipsacaceae , Medicamentos Herbarios Chinos , Animales , Colágeno Tipo I/metabolismo , Medicamentos Herbarios Chinos/farmacología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Farmacología en Red , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Wistar
7.
Analyst ; 146(8): 2632-2637, 2021 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-33660731

RESUMEN

This study reports the development of a new, pH-sensitive, mitochondria-targeting two-photon ratiometric probe (Mito-BNO) for real-time tracking of mitophagy, a process that can be accelerated in brain tissue during stroke. Mito-BNO shows excellent capability for mitochondrial localisation (Pearson's correlation coefficient, r = 0.91), and can also effectively distinguish mitochondria from other subcellular organelles such as lysosomes and the endoplasmic reticulum (r = 0.40 and r = 0.33, respectively). Meanwhile, a rewarding pKa value (5.23 ± 0.03) and the pH reversibility suggest that Mito-BNO can track mitophagy in real time via confocal imaging. Most importantly, the relationship between mitophagy and neuroinflammation during stroke has been successfully demonstrated by evaluating the fluorescence of PC12 cells stained with Mito-BNO during an oxygen-glucose deprivation/reperfusion (OGD/R) process with and without anti-inflammatory treatment. The results indicate that the occurrence of mitophagy during stroke is caused by oxidative stress induced by neuroinflammation. This study will help further understanding stroke pathogenesis, can provide potential new targets for early diagnosis and treatment, and can also help to develop therapeutic drugs for stroke.


Asunto(s)
Mitocondrias , Mitofagia , Accidente Cerebrovascular , Animales , Inflamación/metabolismo , Lisosomas/metabolismo , Ratas
8.
BMC Genomics ; 20(Suppl 9): 912, 2019 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-31874634

RESUMEN

BACKGROUND: Euphorbiaceae is one of the largest families of flowering plants. Due to its exceptional growth form diversity and near-cosmopolitan distribution, it has attracted much interest since ancient times. SBP-box (SBP) genes encode plant-specific transcription factors that play critical roles in numerous biological processes, especially flower development. We performed genome-wide identification and characterization of SBP genes from four economically important Euphorbiaceae species. RESULTS: In total, 77 SBP genes were identified in four Euphorbiaceae genomes. The SBP proteins were divided into three length ranges and 10 groups. Group-6 was absent in Arabidopsis thaliana but conserved in Euphorbiaceae. Segmental duplication played the most important role in the expansion processes of Euphorbiaceae SBP genes, and all the duplicated genes were subjected to purify selection. In addition, about two-thirds of the Euphorbiaceae SBP genes are potential targets of miR156, and some miR-regulated SBP genes exhibited high intensity expression and differential expression in different tissues. The expression profiles related to different stress treatments demonstrated broad involvement of Euphorbiaceae SBP genes in response to various abiotic factors and hormonal treatments. CONCLUSIONS: In this study, 77 SBP genes were identified in four Euphorbiaceae species, and their phylogenetic relationships, protein physicochemical characteristics, duplication, tissue and stress response expression, and potential roles in Euphorbiaceae development were studied. This study lays a foundation for further studies of Euphorbiaceae SBP genes, providing valuable information for future functional exploration of Euphorbiaceae SBP genes.


Asunto(s)
Euphorbiaceae/genética , Familia de Multigenes , Proteínas de Plantas/genética , Factores de Transcripción/genética , Mapeo Cromosómico , Euphorbiaceae/clasificación , Euphorbiaceae/metabolismo , Duplicación de Gen , Genes de Plantas , Genoma de Planta , MicroARNs/metabolismo , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Dominios Proteicos , ARN Mensajero/metabolismo , Sintenía , Factores de Transcripción/química , Factores de Transcripción/metabolismo
9.
BMC Genomics ; 19(Suppl 10): 878, 2018 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-30598104

RESUMEN

BACKGROUND: Species of Paris Sect. Marmorata are valuable medicinal plants to synthesize steroidal saponins with effective pharmacological therapy. However, the wild resources of the species are threatened by plundering exploitation before the molecular genetics studies uncover the genomes and evolutionary significance. Thus, the availability of complete chloroplast genome sequences of Sect. Marmorata is necessary and crucial to the understanding the plastome evolution of this section and facilitating future population genetics studies. Here, we determined chloroplast genomes of Sect. Marmorata, and conducted the whole chloroplast genome comparison. RESULTS: This study presented detailed sequences and structural variations of chloroplast genomes of Sect. Marmorata. Over 40 large repeats and approximately 130 simple sequence repeats as well as a group of genomic hotspots were detected. Inverted repeat contraction of this section was inferred via comparing the chloroplast genomes with the one of P. verticillata. Additionally, almost all the plastid protein coding genes were found to prefer ending with A/U. Mutation bias and selection pressure predominately shaped the codon bias of most genes. And most of the genes underwent purifying selection, whereas photosynthetic genes experienced a relatively relaxed purifying selection. CONCLUSIONS: Repeat sequences and hotspot regions can be scanned to detect the intraspecific and interspecific variability, and selected to infer the phylogenetic relationships of Sect. Marmorata and other species in subgenus Daiswa. Mutation and natural selection were the main forces to drive the codon bias pattern of most plastid protein coding genes. Therefore, this study enhances the understanding about evolution of Sect. Marmorata from the chloroplast genome, and provide genomic insights into genetic analyses of Sect. Marmorata.


Asunto(s)
Evolución Molecular , Genoma del Cloroplasto/genética , Liliaceae/genética , Secuencias Repetitivas de Ácidos Nucleicos/genética , Codón/genética , Genes del Cloroplasto/genética , Genómica , Filogenia
10.
BMC Med Genet ; 19(1): 111, 2018 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-29976160

RESUMEN

BACKGROUND: Ankylosing spondylitis (AS) is a debilitating autoimmune disease affecting tens of millions of people in the world. The genetics of AS is unclear. Analysis of rare AS pedigrees might facilitate our understanding of AS pathogenesis. METHODS: We used genome-wide linkage analysis and whole-exome sequencing in combination with variant co-segregation verification and haplotype analysis to study an AS pedigree and a sporadic AS patient. RESULTS: We identified a missense variant in the ankyrin repeat and death domain containing 1B gene ANKDD1B from a Han Chinese pedigree with dominantly inherited AS. This variant (p.L87V) co-segregates with all male patients of the pedigree. In females, the penetrance of the symptoms is incomplete with one identified patient out of 5 carriers, consistent with the reduced frequency of AS in females of the general population. We further identified a distinct missense variant affecting a conserved amino acid (p.R102L) of ANKDD1B in a male from 30 sporadic early onset AS patients. Both variants are absent in 500 normal controls. We determined the haplotypes of four major known AS risk loci, including HLA-B*27, 2p15, ERAP1 and IL23R, and found that only HLA-B*27 is strongly associated with patients in our cohort. CONCLUSIONS: Together these results suggest that ANKDD1B variants might be associated with AS and genetic analyses of more AS patients are warranted to verify this association.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Mutación Missense/genética , Espondilitis Anquilosante/genética , Adolescente , Adulto , Aminoácidos/genética , Aminopeptidasas/genética , Pueblo Asiatico/genética , Estudios de Casos y Controles , Preescolar , Estudios de Cohortes , Femenino , Ligamiento Genético/genética , Haplotipos/genética , Humanos , Masculino , Antígenos de Histocompatibilidad Menor/genética , Linaje , Receptores de Interleucina/genética , Adulto Joven
11.
RNA Biol ; 15(10): 1295-1308, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30295127

RESUMEN

A key step in pre-mRNA splicing is the recognition of 3' splicing sites by the U2AF large and small subunits, a process regulated by numerous trans-acting splicing factors. How these trans-acting factors interact with U2AF in vivo is unclear. From a screen for suppressors of the temperature-sensitive (ts) lethality of the C. elegans U2AF large subunit gene uaf-1(n4588) mutants, we identified mutations in the RNA binding motif gene rbm-5, a homolog of the tumor suppressor gene RBM5. rbm-5 mutations can suppress uaf-1(n4588) ts-lethality by loss of function and neuronal expression of rbm-5 was sufficient to rescue the suppression. Transcriptome analyses indicate that uaf-1(n4588) affected the expression of numerous genes and rbm-5 mutations can partially reverse the abnormal gene expression to levels similar to that of wild type. Though rbm-5 mutations did not obviously affect alternative splicing per se, they can suppress or enhance, in a gene-specific manner, the altered splicing of genes in uaf-1(n4588) mutants. Specifically, the recognition of a weak 3' splice site was more susceptible to the effect of rbm-5. Our findings provide novel in vivo evidence that RBM-5 can modulate UAF-1-dependent RNA splicing and suggest that RBM5 might interact with U2AF large subunit to affect tumor formation.


Asunto(s)
Empalme Alternativo/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Ciclo Celular/genética , Proteínas de Unión al ADN/genética , Neoplasias/genética , Proteínas de Unión al ARN/genética , Ribonucleoproteínas/genética , Proteínas Supresoras de Tumor/genética , Animales , Animales Modificados Genéticamente/genética , Caenorhabditis elegans/genética , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica , Humanos , Mutación , Neoplasias/patología , Neuronas/metabolismo , Sitios de Empalme de ARN/genética , Empalme del ARN/genética , Factor de Empalme U2AF/genética , Temperatura
12.
Int J Mol Sci ; 19(6)2018 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-29844264

RESUMEN

Physic nut (Jatropha curcas L.) is a species of flowering plant with great potential for biofuel production and as an emerging model organism for functional genomic analysis, particularly in the Euphorbiaceae family. DNA binding with one finger (Dof) transcription factors play critical roles in numerous biological processes in plants. Nevertheless, the knowledge about members, and the evolutionary and functional characteristics of the Dof gene family in physic nut is insufficient. Therefore, we performed a genome-wide screening and characterization of the Dof gene family within the physic nut draft genome. In total, 24 JcDof genes (encoding 33 JcDof proteins) were identified. All the JcDof genes were divided into three major groups based on phylogenetic inference, which was further validated by the subsequent gene structure and motif analysis. Genome comparison revealed that segmental duplication may have played crucial roles in the expansion of the JcDof gene family, and gene expansion was mainly subjected to positive selection. The expression profile demonstrated the broad involvement of JcDof genes in response to various abiotic stresses, hormonal treatments and functional divergence. This study provides valuable information for better understanding the evolution of JcDof genes, and lays a foundation for future functional exploration of JcDof genes.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Estudio de Asociación del Genoma Completo , Jatropha , Familia de Multigenes , Proteínas de Plantas , Factores de Transcripción , Jatropha/genética , Jatropha/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
13.
Mol Ecol ; 26(12): 3276-3294, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28281334

RESUMEN

Clarifying the relationship between distribution patterns of organisms and geological events is critical to understanding the impact of environmental changes on organismal evolution. Quercus sect. Heterobalanus is now distributed across the Himalaya-Hengduan Mountains (HHM) and warm lowland in East China, yet how the distribution patterns of this group changed in response to the HHM uplift remains largely unknown. This study examines the effect of tectonic events in the HHM region on the oaks, providing a biological perspective on the geological history of this region. Fifty-six populations of Quercus sect. Heterobalanus were genotyped using four chloroplast DNA regions and nine nuclear simple sequence repeat loci to assess population structure and diversity, supplemented by molecular dating and ancestral area reconstructions. The underlying demographic dynamics were compared using ecological niche models of the species distributions during the last glacial maximum and the present. These analyses illustrate that Quercus sect. Heterobalanus diversified as the HHM uplifted and climatic cooling during the mid-Miocene, colonizing the cold habitats from warm broadleaf mixed forests. Lineages in cold highlands and warm lowlands have diverged as a consequence of local adaptation to diverging climates since the late Miocene. Our results suggest that continuous uplift of the HHM in the late Miocene to early Pliocene accompanied by simultaneous cooling triggered the differentiation of oaks. The biogeography of Quercus sect. Heterobalanus illuminates the geological events responsible for the modern-day HHM.


Asunto(s)
Ecosistema , Dispersión de las Plantas , Quercus/genética , China , ADN de Cloroplastos/genética , Fenómenos Geológicos , Repeticiones de Microsatélite , Filogenia , Filogeografía
14.
PLoS Genet ; 8(7): e1002827, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22829783

RESUMEN

RNA splicing is a major regulatory mechanism for controlling eukaryotic gene expression. By generating various splice isoforms from a single pre-mRNA, alternative splicing plays a key role in promoting the evolving complexity of metazoans. Numerous splicing factors have been identified. However, the in vivo functions of many splicing factors remain to be understood. In vivo studies are essential for understanding the molecular mechanisms of RNA splicing and the biology of numerous RNA splicing-related diseases. We previously isolated a Caenorhabditis elegans mutant defective in an essential gene from a genetic screen for suppressors of the rubberband Unc phenotype of unc-93(e1500) animals. This mutant contains missense mutations in two adjacent codons of the C. elegans microfibrillar-associated protein 1 gene mfap-1. mfap-1(n4564 n5214) suppresses the Unc phenotypes of different rubberband Unc mutants in a pattern similar to that of mutations in the splicing factor genes uaf-1 (the C. elegans U2AF large subunit gene) and sfa-1 (the C. elegans SF1/BBP gene). We used the endogenous gene tos-1 as a reporter for splicing and detected increased intron 1 retention and exon 3 skipping of tos-1 transcripts in mfap-1(n4564 n5214) animals. Using a yeast two-hybrid screen, we isolated splicing factors as potential MFAP-1 interactors. Our studies indicate that C. elegans mfap-1 encodes a splicing factor that can affect alternative splicing.


Asunto(s)
Empalme Alternativo/genética , Caenorhabditis elegans/genética , Proteínas Contráctiles/genética , Proteínas de la Matriz Extracelular/genética , Precursores del ARN/genética , Sitios de Empalme de ARN/genética , Secuencia de Aminoácidos , Animales , Animales Modificados Genéticamente , Proteínas de Caenorhabditis elegans/genética , Exones/genética , Expresión Génica , Intrones/genética , Proteínas de la Membrana/genética , Datos de Secuencia Molecular , Mutación Missense/genética , Proteínas Nucleares/genética , Fenotipo , Isoformas de Proteínas , Factores de Empalme de ARN , Ribonucleoproteínas/genética , Homología de Secuencia de Aminoácido
15.
RNA Biol ; 11(9): 1148-60, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25483032

RESUMEN

Spinal muscular atrophy (SMA), the most frequent human congenital motor neuron degenerative disease, is caused by loss-of-function mutations in the highly conserved survival motor neuron gene SMN1. Mutations in SMN could affect several molecular processes, among which aberrant pre-mRNA splicing caused by defective snRNP biogenesis is hypothesized as a major cause of SMA. To date little is known about the interactions of SMN with other splicing factor genes and how SMN affects splicing in vivo. The nematode Caenorhabditis elegans carries a single ortholog of SMN, smn-1, and has been used as a model for studying the molecular functions of SMN. We analyzed RNA splicing of reporter genes in an smn-1 deletion mutant and found that smn-1 is required for efficient splicing at weak 3' splice sites. Genetic studies indicate that the defective lifespan and motor functions of the smn-1 deletion mutants could be significantly improved by mutations of the splicing factor U2AF large subunit gene uaf-1. In smn-1 mutants we detected a reduced expression of U1 and U5 snRNAs and an increased expression of U2, U4 and U6 snRNAs. Our study verifies an essential role of smn-1 for RNA splicing in vivo, identifies the uaf-1 gene as a potential genetic modifier of smn-1 mutants, and suggests that SMN-1 has multifaceted effects on the expression of spliceosomal snRNAs.


Asunto(s)
Envejecimiento/genética , Animales Modificados Genéticamente/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Neuronas Motoras/fisiología , Proteínas Nucleares/metabolismo , Ribonucleoproteínas/metabolismo , Proteína 1 para la Supervivencia de la Neurona Motora/metabolismo , Animales , Animales Modificados Genéticamente/genética , Animales Modificados Genéticamente/crecimiento & desarrollo , Conducta Animal , Caenorhabditis elegans/genética , Caenorhabditis elegans/crecimiento & desarrollo , Proteínas de Caenorhabditis elegans/genética , Humanos , Mutación/genética , Proteínas Nucleares/genética , Precursores del ARN/genética , Precursores del ARN/metabolismo , Empalme del ARN , Ribonucleoproteínas/genética , Ribonucleoproteínas Nucleares Pequeñas/genética , Ribonucleoproteínas Nucleares Pequeñas/metabolismo , Factor de Empalme U2AF , Proteína 1 para la Supervivencia de la Neurona Motora/genética
16.
Artículo en Inglés | MEDLINE | ID: mdl-39024013

RESUMEN

Targeting liver cancer stem cells (LCSCs) is a promising strategy for hepatocellular carcinoma (HCC) therapy. Target selection and corresponding inhibitor screening are of vital importance for eliminating the stemness of LCSCs. Peptide-based agents are hopeful but have long been hindered for in vivo application. Herein, we selected a clinically significant target MUC13 and screened out a suitable peptide for preparation of an albumin-based MUC13 peptide nanomedicine, P3@HSA, which suppressed liver cancer stem cells via JNK-ERK signaling pathway-mediated autophagy inhibition. The selected target MUC13 was highly expressed in LCSCs and associated with the prognosis of liver cancer patients. Encouraged by this observation, we screened the corresponding peptide-based inhibitor P3 for further evaluation. P3 could interact with albumin through the intrinsic hydrophobic force and formed the nanomedicine P3@HSA. The prepared nanomedicine could inhibit LCSCs through JNK-ERK signaling pathway-mediated autophagy inhibition and exert potent antitumor effect both in vitro and in vivo. Together, this study provides a promising peptide-based nanomedicine for high-performance HCC treatment.

17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(1): 151-4, 2013 Jan.
Artículo en Zh | MEDLINE | ID: mdl-23586245

RESUMEN

The Er3+ and Yb3+ doped Y2O3 Nano powder was prepared by sol-gel method. Based on 2H11/2 --> 4I15/2 and 4S3/2 --> 4I15/2 green conversion luminescence intensity rate of Er3+, the sample surface temperature changes caused by the increase in 980 nm diode laser pump power were studied. The results show that with pump power increasing, the sample surface temperature substantially rises. And the surface temperature reached to 820 K when the pump power was 1 000 mW. The phenomenon plays an important role in the analysis of upconversion process, especially with saturation power. And this feature has a potential application prospect in the biomedicine, soft tissue hole burning as well as the field of temperature sensing materials.


Asunto(s)
Tecnología Biomédica , Erbio/química , Nanoestructuras/química , Iterbio/química , Calor , Rayos Láser
18.
Exp Ther Med ; 25(3): 129, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36845961

RESUMEN

Endoscopic submucosal dissection (ESD) has been widely used in the treatment of gastrointestinal tract lesions, and hemorrhage is one of the most common complications. The aim of the present study was to investigate the clinical characteristics of hemorrhage after ESD in patients with acquired hemophilia A (AHA). Firstly, a case of AHA with multiple bleeding events after ESD is reported. Colonoscopy was used to perform ESD treatment of the submucosal tumor, and immunohistochemical analysis was used to analyze the tumor properties. Secondly, literature relevant to postoperative hemorrhage caused by AHA was researched and analyzed, with the changes in activated partial thromboplastin time (APTT) before and after operation, coagulation factor VIII (FVIII) activity, FVIII inhibitor value and treatment plan noted. The majority of patients with AHA had no history of coagulation disorder or genetic disease and showed a normal APTT. However, it was found that the APTT value gradually increased after bleeding. In addition, the APTT correction test did not correct for prolonged APTT and FVIII antibody positivity in AHA. There was no bleeding or bleeding tendency prior to surgery in patients with AHA. The study concludes that when repeated bleeding and a poor hemostatic effect occurs, it is necessary to be alerted to the possibility of AHA, as an early diagnosis is essential for effective hemostasis.

19.
Int Immunopharmacol ; 115: 109650, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36649673

RESUMEN

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first appeared in Wuhan, China, in December 2019. The 2019 coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2, has spread to almost all corners of the world at an alarming rate. Vaccination is important for the prevention and control of the COVID-19 pandemic. Efforts are underway worldwide to develop an effective vaccine against COVID-19 using both traditional and innovative vaccine strategies. Compared to other vaccine platforms, SARS-CoV-2 virus-like particles (VLPs )vaccines, as a new vaccine platform, have unique advantages: they have artificial nanostructures similar to natural SARS-CoV-2, which can stimulate good cellular and humoral immune responses in the organism; they have no viral nucleic acids, have good safety and thermal stability, and can be mass-produced and stored; their surfaces can be processed and modified, such as the adjuvant addition, etc.; they can be considered as an ideal platform for COVID-19 vaccine development. This review aims to shed light on the current knowledge and progress of VLPs vaccines against COVID-19, especially those undergoing clinical trials.


Asunto(s)
COVID-19 , Vacunas Virales , Humanos , Vacunas contra la COVID-19 , SARS-CoV-2 , COVID-19/prevención & control , Pandemias/prevención & control
20.
Opt Express ; 20(16): 18127-37, 2012 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-23038360

RESUMEN

Ho(3+)/Yb(3+) codoped glass ceramic was prepared by melt-quenching and subsequent thermal treatment. Under a 980 nm diode laser excitation, upconversion emissions from Ho(3+) ions centered at 540, 650, and 750 nm were greatly enhanced compared with those in the precursor glass. Especially, the short-wavelength upconversion emissions centered at 360, 385, 418, 445, and 485 nm were successfully obtained in the glass ceramic. An explanation for this phenomenon is given based on the fluorescence decay curve measurements. In addition, an optical temperature sensor based on the blue upconversion emissions from (5)F(2,3)/(3)K(8)→(5)I(8) and (5)F(1)/(5)G(6)→(5)I(8) transitions in Ho(3+)/Yb(3+) codoped glass ceramic has been developed. It was found that by using fluorescence intensity ratio technique, appreciable sensitivity for temperature measurement can be achieved by using the Ho(3+)/Yb(3+) codoped glass ceramic. This result makes the Ho(3+)/Yb(3+) codoped glass ceramic be a promising candidate for sensitive optical temperature sensor with high resolution and good accuracy.

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