RESUMEN
Blastoid or pleomorphic mantle cell lymphoma (B/P-MCL) is characterized by high invasiveness and unfavorable outcomes, which is still a challenge for treating MCL. This retrospective study was performed to comprehensively analyze the clinical, genomic characteristics and treatment options of patients with B/PMCL from multicenter in China. Data were obtained from 693 patients with B/PMCL from three centers in China between April 1999 and December 2019. Seventy-four patients with BMCL (n = 43) or PMCL (n = 31) were included in the analysis. The median age of the cohort was 60.0 years with a male-to-female ratio of 2.89:1. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 44.1% and 46.0%, respectively. Mutations of TP53, ATM, NOTCH1, NOTCH2, NSD2, SMARCA4, CREBBP, KMT2D, FAT1, and TRAF2 genes were the most common genetic changes in B/P-MCL. Progression of disease within 12 months (POD12) could independently predict the poor prognosis of patients with blastoid and pleomorphic variants. Patients with POD12 carried a distinct mutation profile (TP53, SMARCA4, NSD2, NOTCH2, KMT2D, PTPRD, CREBBP, and CDKN2A mutations) compared to patients with non-POD12. First-line high-dose cytosine arabinoside exposure obtained survival benefits in these populations, and BTKi combination therapy as the front-line treatment had somewhat improvement in survival with no significant difference in the statistic. In conclusion, B/P-MCL had inferior outcomes and a distinct genomic profile. Patients with POD12 displayed a distinct mutation profile and a poor prognosis. New therapeutic drugs and clinical trials for B/P-MCL need to be further explored.
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Linfoma de Células del Manto , Mutación , Humanos , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/mortalidad , Linfoma de Células del Manto/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Estudios Retrospectivos , Anciano , Adulto , Pronóstico , Tasa de Supervivencia , Anciano de 80 o más AñosRESUMEN
During the freeze-thaw process, human spermatozoa are susceptible to oxidative stress, which may cause cryodamage and reduce sperm quality. As a novel mitochondria-targeted antioxidant, Mito-tempo has been used for sperm cryopreservation. However, it is currently unknown what role it will play in the process of sperm ultra-rapid freezing. The purpose of this study was to investigate whether Mito-tempo can improve sperm quality during ultra-rapid freezing. In this study, samples with the addition of Mito-tempo (0, 5, 10, 20, and 40 µM) to sperm freezing medium were selected to evaluate the changes in sperm quality, antioxidant capacity and ultrastructure after ultra-rapid freezing. After ultra-rapid freezing, the quality and antioxidant function of the spermatozoa were significantly reduced and the spermatozoa ultrastructure was destroyed. The addition of 10 µM Mito-tempo significantly increased post thaw sperm motility, viability, plasma membrane integrity and mitochondrial membrane potential (P < 0.05). Moreover, the DNA fragmentation index (DFI), ROS levels and MDA content were reduced, and the antioxidant enzyme (CAT and SOD) activities were enhanced in the 10 µM Mito-tempo group (P < 0.05). Moreover, Mito-tempo protected sperm ultrastructure from damage. In conclusion, Mito-tempo improved the quality and antioxidant function of sperm after ultra-rapid freezing while reducing freezing-induced ultrastructural damage.
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Antioxidantes , Preservación de Semen , Masculino , Humanos , Antioxidantes/farmacología , Congelación , Criopreservación/métodos , Motilidad Espermática , Crioprotectores/farmacología , Semen , Espermatozoides , MitocondriasRESUMEN
RESEARCH QUESTION: Non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) avoids the possible detrimental impact of invasive PGT-A on embryo development and clinical outcomes. Does cell-free DNA (cfDNA) from spent blastocyst culture medium (BCM) reflect embryonic chromosome status better than trophectoderm (TE) biopsy? DESIGN: In this study, 35 donated embryos were used for research and the BCM, TE biopsy, inner cell mass (ICM) and residual blastocyst (RB) were individually picked up from these embryos. Whole genome amplification (WGA) was performed and amplified DNA was subject to next-generation sequencing. Chromosome status concordance was compared among the groups of samples. RESULTS: The WGA success rates were 97.0% (TE biopsy), 100% (ICM), 97.0% (RB) and 88.6% (BCM). Using ICM as the gold standard, the chromosomal ploidy concordance rates for BCM, TE biopsy and RB were 58.33% (14/24), 68.75% (22/32) and 78.57% (22/28); the diagnostic concordance rates were 83.33% (20/24), 87.50% (28/32) and 92.86% (26/28); and the sex concordance rates were 92.31% (24/26), 100% (32/32) and 100% (28/28), respectively. Considering RB the gold standard, the chromosome ploidy concordance rates for BCM and TE biopsy were 61.90% (13/21) and 81.48% (22/27); the diagnostic concordance rates were 71.43% (15/21) and 88.89% (24/27); and the sex concordance rates were 91.30% (21/23) and 100% (27/27), respectively. CONCLUSIONS: The results of niPGT-A of cfDNA of spent BCM are comparable to those of invasive PGT-A of TE biopsies. Modifications of embryo culture conditions and testing methods will help reduce maternal DNA contamination and improve the reliability of niPGT-A.
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Ácidos Nucleicos Libres de Células , Diagnóstico Preimplantación , Embarazo , Femenino , Humanos , Diagnóstico Preimplantación/métodos , Reproducibilidad de los Resultados , Blastocisto/patología , Aneuploidia , Pruebas Genéticas/métodos , BiopsiaRESUMEN
The endophytic fungus Nigrospora sphaerica S5 derived from the semi-mangrove plant Myoporum bontioides was fermented. Its metabolites were purified by column chromatography. Nine compounds were obtained and identified as terezine P(1), 3-(1-hydroxyethyl)-4-methyl dihydrofuran-2(3H)-one(2), methylhydroheptelidate(3), hydroheptelidic acid(4), 5, 7-dimethoxy-4, 6-dimethylphthalide(5),(3R,4S)-(-)-4-hydroxymellein(6), pestalopyrone(7), indole-3-formaldehyde(8) and p-hydroxybenzaldehyde(9) by spectroscopic techniques. Terezine P(1) was a new alkaloid belonging to the terezine class with a pyrazine ring. Compounds 2-7 were lactones, of which 3 and 4 belonged to sesquiterpenes. Compounds 8 and 9 were indole alkaloids and phenols, respectively. Compounds 3-6 were purified from Nigrospora sp. for the first time. These compounds showed different degrees of antibacterial activity against Staphylococcus aureus, Escherichia coli of O6 serotype and E. coli of O78 serotype.
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Alcaloides , Ascomicetos , Myoporum , Sesquiterpenos , Antibacterianos/farmacología , Ascomicetos/química , Escherichia coli , Formaldehído , Indoles/farmacología , Lactonas , Estructura Molecular , Myoporum/química , Myoporum/microbiología , Fenoles , PirazinasRESUMEN
Unlike other members of the polycomb group protein family, EZH1 has been shown to positively associate with active transcription on a genome-wide scale. However, the underlying mechanism for this behavior still remains elusive. Here, we report that EZH1 physically interacts with UXT, a small chaperon-like transcription co-activator. UXT specifically interacts with EZH1 and SUZ12, but not EED. Similar to upon knockdown of UXT, knockdown of EZH1 or SUZ12 through RNA interference in the cell impairs the transcriptional activation of nuclear factor (NF)-κB target genes induced by TNFα. EZH1 deficiency also increases TNFα-induced cell death. Interestingly, chromatin immunoprecipitation and the following next-generation sequencing analysis show that H3K27 mono-, di- and tri-methylation on NF-κB target genes are not affected in EZH1- or UXT-deficient cells. EZH1 also does not affect the translocation of the p65 subunit of NF-κB (also known as RELA) from the cytosol to the nucleus. Instead, EZH1 and SUZ12 regulate the recruitment of p65 and RNA Pol II to target genes. Taken together, our study shows that EZH1 and SUZ12 act as positive regulators for NF-κB signaling and demonstrates that EZH1, SUZ12 and UXT work synergistically to regulate pathway activation in the nucleus.
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Regulación de la Expresión Génica , FN-kappa B/metabolismo , Proteínas de Neoplasias/metabolismo , Complejo Represivo Polycomb 2/metabolismo , Transcripción Genética , Apoptosis/efectos de los fármacos , Proteínas de Ciclo Celular , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Células HCT116 , Histonas/metabolismo , Humanos , Lisina/metabolismo , Metilación/efectos de los fármacos , Chaperonas Moleculares , Unión Proteica/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , ARN Polimerasa II/metabolismo , Factor de Transcripción ReIA/metabolismo , Factores de Transcripción , Transcripción Genética/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
In this study, we used a systems biology approach to investigate changes in the proteome and metabolome of shrimp hemocytes infected by the invertebrate virus WSSV (white spot syndrome virus) at the viral genome replication stage (12 hpi) and the late stage (24 hpi). At 12 hpi, but not at 24 hpi, there was significant up-regulation of the markers of several metabolic pathways associated with the vertebrate Warburg effect (or aerobic glycolysis), including glycolysis, the pentose phosphate pathway, nucleotide biosynthesis, glutaminolysis and amino acid biosynthesis. We show that the PI3K-Akt-mTOR pathway was of central importance in triggering this WSSV-induced Warburg effect. Although dsRNA silencing of the mTORC1 activator Rheb had only a relatively minor impact on WSSV replication, in vivo chemical inhibition of Akt, mTORC1 and mTORC2 suppressed the WSSV-induced Warburg effect and reduced both WSSV gene expression and viral genome replication. When the Warburg effect was suppressed by pretreatment with the mTOR inhibitor Torin 1, even the subsequent up-regulation of the TCA cycle was insufficient to satisfy the virus's requirements for energy and macromolecular precursors. The WSSV-induced Warburg effect therefore appears to be essential for successful viral replication.
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Penaeidae/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Virus del Síndrome de la Mancha Blanca 1/genética , Aminoácidos/biosíntesis , Aminoácidos/metabolismo , Animales , Ciclo del Ácido Cítrico/genética , Metabolismo Energético/genética , Glucólisis/genética , Diana Mecanicista del Complejo 1 de la Rapamicina , Diana Mecanicista del Complejo 2 de la Rapamicina , Metaboloma/genética , Proteínas de Unión al GTP Monoméricas/genética , Complejos Multiproteicos/antagonistas & inhibidores , Complejos Multiproteicos/genética , Naftiridinas/farmacología , Penaeidae/virología , Vía de Pentosa Fosfato/genética , Proteoma/genética , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/genética , Replicación Viral/genética , Virus del Síndrome de la Mancha Blanca 1/metabolismoRESUMEN
To elucidate the intervention effects of Jiaotai pills(JTP) on p-chlorophenylalanine (PCPA)-induced insomnia in rats and its underlying mechanism, the insomnia model was established by single intraperitoneal injection with PCPA in rats. The locomotor activity of rats was observed, and the levels of nerve growth factor(NGF) in hypothalamus, hippocampus, prefrontal cortex and serum of rats were determined by using ELISA. Moreover, a proton nuclear magnetic resonance(¹H-NMR)-based metabonomic approach was developed to profile insomnia-related metabolites in rat serum and hippocampus and analyze the intervention effects of JTP on changes in underlying biomarkers related to locomotor activity, NGF and insomnia. According to the results, JTP could significantly suppress the locomotor activity of insomnia rats, and increase the NGF levels in hypothalamus, hippocampus, prefrontal cortex and serum of rats with insomnia. The disturbed metabolic state associated with PCPA-induced insomnia in rat serum and hippocampus could be intervened by JTP. Meanwhile, six and five potential biomarkers related to insomnia in rat serum and hippocampus were reversed by administration of JTP. In conclusion, the current study demonstrated that JTP had protective effects against PCPA-induced insomnia in rats, which was probably correlated with regulation of NGF level and metabolism of amino acids, lipids and choline.
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Medicamentos Herbarios Chinos/farmacología , Hipocampo/efectos de los fármacos , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Animales , Factor de Crecimiento Nervioso/metabolismo , Ratas , Trastornos del Inicio y del Mantenimiento del Sueño/inducido químicamenteRESUMEN
A new di-O-prenylated flavone, named 7,3'-di-(γ,γ-dimethylallyloxy)-5-hydroxy-4'-methoxyflavone (1), was isolated from the culture broth of the endophytic actinomycete Streptomyces sp. MA-12 isolated from the root of the semi-mangrove plant Myoporum bontioides A. Gray. The structure of 1 was determined by comprehensive spectroscopic methods, including 1D and 2D NMR experiments (COSY, HMQC, and HMBC). Primary bioassays showed that 1 at concentration of 0.25 mM had moderate inhibitory activity against three plant pathogenic fungi including Colletotrichum musae, Gibberella zeae (Schweinitz) Petch, and Penicillium citrinum Thom.
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Antifúngicos/aislamiento & purificación , Flavonas/aislamiento & purificación , Myoporum/microbiología , Streptomyces/química , Antifúngicos/química , Antifúngicos/farmacología , Flavonas/química , Flavonas/farmacología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Raíces de Plantas/microbiologíaRESUMEN
In addition to the Warburg effect, which increases the availability of energy and biosynthetic building blocks in WSSV-infected shrimp, WSSV also induces both lipolysis at the viral genome replication stage (12 hpi) to provide material and energy for the virus replication, and lipogenesis at the viral late stage (24 hpi) to complete virus morphogenesis by supplying particular species of long-chain fatty acids (LCFAs). Here, we further show that WSSV causes a reduction in lipid droplets (LDs) in hemocytes at the viral genome replication stage, and an increase in LDs in the nuclei of WSSV-infected hemocytes at the viral late stage. In the hepatopancreas, lipolysis is triggered by WSSV infection, and this leads to fatty acids being released into the hemolymph. ß-oxidation inhibition experiment reveals that the fatty acids generated by WSSV-induced lipolysis can be diverted into ß-oxidation for energy production. At the viral late stage, WSSV infection leads to lipogenesis in both the stomach and hepatopancreas, suggesting that fatty acids are in high demand at this stage for virion morphogenesis. Our results demonstrate that WSSV modulates lipid metabolism specifically at different stages to facilitate its replication.
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Penaeidae , Virus del Síndrome de la Mancha Blanca 1 , Animales , Metabolismo de los Lípidos , Virus del Síndrome de la Mancha Blanca 1/fisiología , Oxidación-Reducción , Ácidos Grasos/metabolismoRESUMEN
Melatonin is a key neuroendocrine hormone that promotes spermatogenesis and sperm motility, but the underlying mechanisms remains poorly understood. In this study, we aimed to investigate the possible roles of m6A (N6--methyl-adenosine) in mediating melatonin-regulated spermatogonia activity alterations. In this study, mouse-derived GC-1 spermatogonia (spg) cell line was used as the in vitro cellular model. The viability, proliferation rates and apoptosis of spermatogonia were detected via CCK-8, Edu staining and flow cytometry respectively. Total m6A level was quantitated by dot blot, while mRNA and proteins contents in spermatogonia were measured by qRT-PCR and western blot respectively. Differentially expressed mRNAs were characterized by deep RNA sequencing method. Results showed that melatonin significantly promoted viability and proliferation rate while inhibited apoptosis in the GC-1 spg cells. The total m6A levels in GC-1 spg cells were also greatly increased by melatonin treatment, accompanied by remarkable expressional elevation of the m6A writer KIAA1429. Moreover, the regulation of GC-1 spg cell viability, proliferation and apoptosis by melatonin were greatly abrogated by KIAA1429 silencing but effectively strengthened by KIAA1429 overexpression. In addition, KIAA1429 overexpression regulates multiple biological process and signaling pathways in spermatogonia such as the PI3K/AKT signaling. The PI3K inhibitor LY294002 effectively mitigated the regulation of spermatogonia activity by KIAA1429 overexpression under melatonin treatment. Taken together, melatonin promotes spermatogonia activity via enhancing KIAA1429 expression and m6A RNA methylation to activate the downstream PI3K/AKT signaling pathway.
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Adenosina , Melatonina , Proteínas de Unión al ARN , Espermatogonias , Animales , Masculino , Ratones , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Melatonina/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/metabolismo , Transducción de Señal , Motilidad Espermática , Espermatogonias/metabolismo , Proteínas de Unión al ARN/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismoRESUMEN
Four new diphenyl ethers, named epicoccethers K-N (1-4), were purified from the fermentation medium of a fungus Epicoccum sorghinum derived from Myoporum bontioides, and identified through HR-ESI-MS and NMR spectral analysis. Except that compound 1 showed moderate antifungal activity against Penicillium italicum and Fusarium graminearum, the other three compounds showed stronger activity against them than triadimefon. All of them showed moderate or weak antibacterial activity towards Staphylococcus aureus and Escherichia coli with O6 and O78 serotypes except that 3 was inactive to E. coli O6.
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Ascomicetos , Escherichia coli , Antibacterianos/farmacología , Antifúngicos/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Éteres Fenílicos/químicaRESUMEN
PURPOSE: In most cases, the carcinogenesis of colorectal cancer (CRC) follows the normal-adenoma-carcinoma (N-A-C) sequence. In this study, we aimed to identify the key proteins in the N-A-C sequence. METHODS: Differentially expressed proteins (DEPs) in normal, adenoma, and carcinoma tissues were identified using the Tandem Mass Tag- (TMT-) based quantitative proteomics approach. The landscape of proteomic variation in the N-A-C sequence was explored using gene set enrichment analysis (GSEA) and Proteomaps. Key proteins in the N-A-C sequence were identified, verified, and validated based on our proteomic data, external proteomic data, and external transcriptomic data in the ProteomeXchange, CPTAC, GEO, and TCGA databases. The prognostic value of the key proteins in our database was evaluated by univariate and multivariate Cox regression analysis. The effects of the key proteins on adenoma organoids and colorectal cancer cells were explored in functional studies. RESULTS: Based on our proteomic profiles, we identified 1,294 DEPs between the carcinoma (CG) and normal (NG) groups, 919 DEPs between the adenoma group (AG) and NG, and 1,030 DEPs between the CG and AG. Ribosome- and spliceosome-related pathways were mainly enriched in the N-A process. Extracellular matrix- and epithelial-mesenchymal transition- (EMT-) related pathways were mainly enriched in the A-C process. RRP12 and SERPINH1 were identified, verified, and validated as candidate key proteins in the N-A and A-C processes, respectively. Furthermore, RRP12 and SERPINH1 knockdown impeded the viability and proliferation of adenoma organoids. SERPINH1 was validated as a risk factor for disease-free survival (DFS) based on the TCGA and our database, whereas RRP12 did not show prognostic value. SERPINH1 knockdown was accompanied by EMT-related protein variation, increased apoptosis, and reduced proliferation, invasion, and migration of CRC cells in vitro. CONCLUSIONS: RRP12 and SERPINH1 may play an important role in the N-A and A-C processes, respectively. Furthermore, SERPINH1 showed favorable prognostic value for DFS in CRC patients. We speculate that SERPINH1 might promote not only the A-C process but also the development of CRC.
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This present study aimed to explore the typical protein features of tubulovillous adenoma (TVA) using proteomic and bioinformatic analyses. Tandem mass tag (TMT)-based quantitative proteomic analyses were conducted on normal mucosa, tubular adenoma, TVA and adenocarcinoma tissues. We identified 5,665 proteins categorized into seven clusters based on Pearson's correlation analysis. The bioinfomatic analysis showed mitochondrial and metabolism-related events were typical characteristics of TVA and mitochondrial-, ribosome- and matrisome-related biological processes may contribute to carcinogenesis. PLOD3 was identified as a key protein associated with the malignant potential of TVA and promoted the viability of adenoma organoids. The Cancer Genome Atlas (TCGA) analysis revealed PLOD3 as a risk factor for disease-free and overall survival. Furthermore, the PLOD3 expression correlated negatively with the abundance of B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages and myeloid dendritic cells. In conclusion, enhanced metabolic and mitochondrial reprogramming are typical features of TVA, and PLOD3 might be related to the "immune desert" phenotype and contribute to TVA tumorigenesis and colorectal cancer development.
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Adenoma , Neoplasias Colorrectales , Proteoma , Adenoma/genética , Adenoma/metabolismo , Adenoma/mortalidad , Adenoma/patología , Animales , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Humanos , Linfocitos/metabolismo , Masculino , Ratones , Procolágeno-Lisina 2-Oxoglutarato 5-Dioxigenasa , Proteoma/análisis , Proteoma/genética , Proteoma/metabolismo , Proteómica , Células Tumorales CultivadasRESUMEN
PURPOSE: In this study, we aimed to provide a comprehensive description of typical features and identify key proteins associated with the high-grade intraepithelial neoplasia- (HIN-) adenocarcinoma (AC) sequence. METHODS: We conducted tandem mass tag-based quantitative proteomic profiling of normal mucosa, HIN, and AC tissues. Protein clusters representative of the HIN-AC sequence were identified using heatmaps based on Pearson's correlation analysis. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, ClueGO plugin in Cytoscape, and the Metascape database. The prognostic value of the key proteins and their effects on the tumor microenvironment and consensus molecular subtype were explored based on The Cancer Genome Atlas. RESULTS: We identified 536 proteins categorized into three clusters. Among the biological processes and pathways of the highly expressed proteins in the HIN-AC sequence, proteins were predominantly enriched in response to gut microbiota, cell proliferation, leukocyte migration, and extracellular matrix (ECM) organization events. SERPINH1 and P3H1 were identified as the key proteins that promote the HIN-AC sequence. In the correlation analysis of infiltrating immune cells, both SERPINH1 and P3H1 expression correlated negatively with tumor purity, while correlating positively with abundance of CD8+ T cells, B cells, macrophage/monocytes, dendritic cells, cancer-associated fibroblasts, endothelial cells, neutrophils, and natural killer cells. Furthermore, both SERPINH1 and P3H1 expression positively correlated with common immune checkpoints and mesenchymal molecular subtype. High P3H1 expression was associated with poor disease-free survival and overall survival. CONCLUSIONS: ECM-related biological processes and pathways are typical features of the HIN-AC sequence. SERPINH1 and P3H1 might be the key proteins in this sequence and be related to ECM remodeling and immune suppression status in CRC.
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A new diimide derivative, named (-)-byssochlamic acid bisdiimide (1), was isolated from the mixed broth of two mangrove fungi (strain no. K38 and E33) from the South China sea coast. The structure of 1 was determined by comprehensive spectroscopic methods, including 1D and 2D NMR (COSY, HMQC, and HMBC) and semi-synthesis. Primary bioassays showed that 1 had weak cytotoxic activity against Hep-2 and HepG2 cells.
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Antineoplásicos/aislamiento & purificación , Hongos/química , Compuestos Heterocíclicos con 3 Anillos/aislamiento & purificación , Imidas/aislamiento & purificación , Antineoplásicos/química , Antineoplásicos/farmacología , China , Ensayos de Selección de Medicamentos Antitumorales , Furanos/química , Furanos/aislamiento & purificación , Células Hep G2 , Compuestos Heterocíclicos con 3 Anillos/química , Compuestos Heterocíclicos con 3 Anillos/farmacología , Humanos , Imidas/química , Imidas/farmacología , Resonancia Magnética Nuclear Biomolecular , EstereoisomerismoRESUMEN
A simple and efficient method for regioselective acylation of mangiferin catalyzed by lipase under ultrasound irradiation is reported. Compared with the conventional methods, its main advantages are shorter reaction time and higher yields. The optimum conditions were screened out. Under the optimal conditions (lipase: PCL, acyl donor: vinyl acetate; reaction solvent: DMSO, reaction temperature: 45 degrees C, ultrasonic power: 200 W; substrate ratio: acyl donor/mangiferin 6/1, enzyme loading: 6 mg/ml), the regioselective acylation yield was up to 84%.
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Lipasa/metabolismo , Lipasa/efectos de la radiación , Xantonas/química , Acilación , Catálisis , Solventes , Estereoisomerismo , Compuestos de Vinilo/química , AguaRESUMEN
Coal and rock burst are one of the main dynamic disasters that affect coal mine production. In this paper, the burst structural model of the rock-coal-bolt (RCB) system and the burst tendency criterion are established on the background of deep thin coal seam mining. Uniaxial and triaxial mechanical tests under different stress states are carried out on RCB specimens with different angles. Combined with thermal imaging, the mechanical behavior of the inclined RCB specimen under uniaxial loading is discussed. The results show that the burst tendency of the RCB specimen increases with the angle. The stress-strain curves of some uniaxial and triaxial test specimens show two or more peaks, and the thermal imaging evolutionary process shows that the cracks of the coal and rock develop from shear to tension shear cracks. There is a further development of fracture and energy accumulation between the first and second peaks in the stress-strain curve of the specimen. Therefore, the failure degree of the second peak of the specimen may be stronger than that of the first peak. Additionally, the established stiffness coefficient and burst energy index can better describe the burst tendency of the RCB specimen under different stress states. The results show that the burst tendency of the RCB specimen under the triaxial test is much higher than that of the uniaxial test. In other words, it also explains that the essence of the burst failure of the surrounding rock in the roadway is the initial instability induced by the inside surrounding rock in the roadway. Moreover, the burst tendency is the largest when the rock and coal combination angle is 15°, and the burst damage range may also be increased by the failure of internal coal and rock mass.
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The title compound, C(10)H(8)O(4), was isolated from the fermentation culture of the endophytic fungus Cephalo-sporium sp. In the crystal structure, mol-ecules are connected into a one-dimensional chain along [101] by inter-molecular O-Hâ¯O hydrogen bonds involving the hydroxyl and carbonyl functionalities. The chains are linked by non-classical C-Hâ¯O inter-actions, forming extended two-dimensional layers approximately parallel to (11).
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White spot syndrome virus (WSSV) is the causative agent of a shrimp disease that has caused huge global economic losses. Although its pathogenesis remains poorly understood, it has been reported that in the shrimp immune cells (hemocytes) targeted by WSSV, the virus triggers both the Warburg effect and glutamine metabolism at the WSSV genome replication stage (12 h post infection). Glutamine metabolism follows two pathways: an oxidative pathway mediated by α-KGDH (α-ketoglutarate dehydrogenase) and an alternative reductive pathway mediated by IDH1 and IDH2 (isocitrate dehydrogenase 1 and 2). Here we used isotopically labeled glutamine ([U-13C]glutamine and [1-13C]glutamine) as metabolic tracers to show that, at the replication stage, both the oxidative and reductive glutamine metabolic pathways were activated. We further show that the mRNA expression levels of α-KGDH and IDH1 were increased in WSSV-infected shrimps and that silencing of α-KGDH, IDH1, and IDH2 with their respective dsRNAs led to a decrease in WSSV gene expression and WSSV replication. Taken together, our findings provide new evidence for WSSV-induced metabolic reprogramming in hemocytes and demonstrate its importance in virus replication.
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Infecciones por Virus ADN/metabolismo , Glutamina/metabolismo , Hemocitos/metabolismo , Replicación Viral , Virus del Síndrome de la Mancha Blanca 1/fisiología , Animales , Infecciones por Virus ADN/genética , Infecciones por Virus ADN/veterinaria , Infecciones por Virus ADN/virología , Genoma Viral , Glutaminasa/genética , Hemocitos/virología , Isocitrato Deshidrogenasa/genética , Complejo Cetoglutarato Deshidrogenasa/genética , Oxidación-Reducción , Penaeidae/metabolismo , Penaeidae/virología , Replicación Viral/genética , Virus del Síndrome de la Mancha Blanca 1/genéticaRESUMEN
BACKGROUND: Protein arginine methylation is a prevalent post-translational modification. The protein arginine methyltransferase family (PRMT) is involved in many cellular processes in eukaryotes, including transcriptional regulation, epigenetic regulation, RNA metabolism, and DNA damage repair. Toxoplasma gondii, an opportunistic protozoan parasite, encodes five conserved PRMTs. PRMT5 is thought to be responsible for substantial PRMT activity in T. gondii; however, it has not yet been characterized. METHODS: We tagged the 3' end of the endogenous TgPRMT5 genomic locus with sequence encoding a 3X hemagglutinin (HA) epitope. IFA and WB were performed to check the expression and subcellular localization of TgPRMT5 in tachyzoites and bradyzoites. In vitro methylation assays were performed to determine whether endogenous TgPRMT5 has arginine methyltransferase activity. RESULTS: IFA and WB results showed that T. gondii PRMT5 (TgPRMT5) was localized in the cytoplasm in the tachyzoite stage; however, it shifts largely to the nuclear compartment in the bradyzoite stage. The in vitro methylation showed that TgPRMT5 has authentic type II PRMT activity and forms monomethylarginines and symmetric dimethylarginines. CONCLUSIONS: We determined the expression and cellular localization of TgPRMT5 in tachyzoites and bradyzoites and confirmed its type II PRMT activity. We demonstrated the major changes in expression and cellular localization of TgPRMT5 during the tachyzoite and bradyzoite stages in T. gondii. Our findings suggest that TgPRMT5 protein may be involved in tachyzoite-bradyzoite transformation.