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1.
J Agric Food Chem ; 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32227945

RESUMO

PEP 1b is a novel immunoregulatory protein isolated from Pleurotus eryngii, a popular edible mushroom. In this study, isobaric tags for relative and absolute quantitation (iTRAQ) approach and bioinformatics analysis were used to characterize the PEP-1b-induced proteome alterations in Raw 264.7 macrophage cells, to comprehensively excavate the molecular mechanisms involved in the immunoregulatory effects of PEP 1b. In comparison to the control group, PEP 1b treatment significantly changed the expression of 292 proteins, including 191 upregulated and 101 downregulated proteins. Bioinformatics analysis showed that PEP-1b-regulated proteins were involved in 437 biological process domains, 131 cellular component domains, and 90 molecular function domains. Moreover, PEP 1b played the role of immunomodulator by mainly modulating the Rap1 signaling pathway, Wnt signaling pathway, Ras signaling pathway, and PI3K-Akt signaling pathway. Interestingly, PEP 1b regulated the proteins involved in the immune system, signal transduction, and transport processes, which were related to the immunoregulatory effects of PEP 1b. The western blotting analysis confirmed that the immune-boosting activities of PEP 1b were associated with modulating the expression of Sqstm1, Cox2, Rap1b, and Pyk2. The current research provided a comprehensive understanding of the immunoregulatory effects and molecular mechanisms involved in the PEP 1b supplementation.

2.
Chem Biol Drug Des ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32167676

RESUMO

Epothilone is a macrolide secondary metabolite which has the same anticancer effect as paclitaxel. Based on a series of single-factor experiments, four factors, temperature, initial pH, rotation speed, and inoculum quantity, which have the greatest influence on yield, were determined. Four factors were designed and orthogonal experiments were carried out to optimize the fermentation conditions. Finally, the best experimental conditions were obtained as follows: 250 ml flapper triangular flask was used. The yield of epothilone B was 39.76 mg/L at 30℃, initial pH = 7.4, rotating speed 200 r/min, inoculation amount 10%, liquid loading amount 50 ml/250 ml, fermentation time 6 days and seed age 60 hr.

3.
Chem Biol Drug Des ; 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32220102

RESUMO

Epothilone is a kind of macrolide compound, which has anticancer activity and strong inhibitory effect on breast cancer and rectal cancer cells. Herein, the chemical and biological synthesis of epothilones and how to improve fermentation yield and separation methods were summarized and discussed.

4.
Proc Natl Acad Sci U S A ; 117(10): 5394-5401, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32094176

RESUMO

As a prototype of genomics-guided precision medicine, individualized thiopurine dosing based on pharmacogenetics is a highly effective way to mitigate hematopoietic toxicity of this class of drugs. Recently, NUDT15 deficiency was identified as a genetic cause of thiopurine toxicity, and NUDT15-informed preemptive dose reduction was quickly adopted in clinical settings. To exhaustively identify pharmacogenetic variants in this gene, we developed massively parallel NUDT15 function assays to determine the variants' effect on protein abundance and thiopurine cytotoxicity. Of the 3,097 possible missense variants, we characterized the abundance of 2,922 variants and found 54 hotspot residues at which variants resulted in complete loss of protein stability. Analyzing 2,935 variants in the thiopurine cytotoxicity-based assay, we identified 17 additional residues where variants altered NUDT15 activity without affecting protein stability. We identified structural elements key to NUDT15 stability and/or catalytical activity with single amino acid resolution. Functional effects for NUDT15 variants accurately predicted toxicity risk alleles in patients treated with thiopurines with far superior sensitivity and specificity compared to bioinformatic prediction algorithms. In conclusion, our massively parallel variant function assays identified 1,152 deleterious NUDT15 variants, providing a comprehensive reference of variant function and vastly improving the ability to implement pharmacogenetics-guided thiopurine treatment individualization.

5.
J Agric Food Chem ; 68(11): 3585-3593, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32096634

RESUMO

Glutenin macropolymer (GMP) plays a pivotal role in improving dough quality. In this study, a novel Lactobacillus plantarum LB-1 (LB-1) on the fermentation characteristics of dough were investigated from the perspective of GMP. The results showed that the ordered secondary structure (α-helices and ß-sheets) content of GMP in dough synergistically fermented by yeast and LB-1 (DYLB-1) was 20.5% more than that in dough fermented by yeast (DY), and the average particle size was 2.46 µm smaller. Moreover, the higher level of total free amino acids and lower free sulfhydryl group (SHf) content in the DYLB-1 indicated that the network structure strength was enhanced. Furthermore, the protein and starch in the DYLB-1 were uniformly and closely connected, which endows the DYLB-1 with excellent rheological and gas production properties. Therefore, the method used to produce the DYLB-1 was recommended as a new strategy for producing high-quality dough.

6.
J Sci Food Agric ; 100(7): 3136-3146, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32096232

RESUMO

BACKGROUND: Fungal contamination in food products leads to mustiness, biochemical changes, and undesirable odors, which result in lower food quality and lower market value. To develop a rapid method for detecting fungi, hyperspectral imaging (HSI) was applied to identify five fungi inoculated on plates (Aspergillus niger, Aspergillus flavus, Penicillium chrysogenum, Aspergillus fumigatus, and Aspergillus ochraceus). Near-infrared (NIR) spectroscopy, mid-infrared (MIR) spectroscopy, and an electronic nose (E-nose) were applied to detect and identify freeze-dried Agaricus bisporus infected with the five fungi. RESULTS: Partial least squares regression (PLSR) models were used to distinguish the HSI spectra of the five fungi on the plates. The A. ochraceus group had the highest calibration performance: coefficient of calibration (Rc 2 ) = 0.786, root mean-square error of calibration (RMSEC) = 0.125 log CFU g-1 . The A. flavus group had the highest prediction performance: coefficient of prediction (Rp 2 ) = 0.821, root mean-square error of prediction (RMSEP) = 0.083 log CFU g-1 . The ratio of performance deviation (RPD) values of all of the models was higher than 2.0 for the NIR, MIR, and E-nose results for freeze-dried A. bisporus infected with different fungi. The fungal species and degree of infection can be distinguished by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) using NIR, MIR, and E-nose, as the discrimination accuracy was more than 90%. The NIR methods had a higher recognition rate than the MIR and E-nose methods. CONCLUSION: Principal component analysis (PCA) and PLSR models based on full spectra of HSI can achieve good discrimination results for these five fungi on plates. Moreover, NIR, MIR, and the E-nose were proven to be effective in monitoring fungal contamination on freeze-dried A. bisporus. However, NIR could be a more accurate method. © 2020 Society of Chemical Industry.

7.
J Food Sci ; 85(2): 493-499, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31985835

RESUMO

The concentrations of heavy metals, such as chromium (Cr), arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb), in different muscles and edible offal of consumed pork from the city of Nanjing and related health risks were evaluated. The results showed that the detected Hg concentrations from 6 of 80 samples exceeded the maximum allowable concentration (GB 2762-2017). Moreover, most of the edible offal, especially the kidneys, contained more heavy metals than the other parts, although the concentrations among the samples were significantly different (P < 0.05). In addition, the health risk evaluation revealed that the estimated daily intake of all the samples was far below the recommended limit, and all the target hazard quotients and total target hazard quotients were less than 1, which is considered safe for human health. Nevertheless, the Hg concentrations over the acceptable limit should receive sufficient attention, considering the long-term consumption of pork. PRACTICAL APPLICATION: Currently, no reports have been available on the heavy metal assessment of pork, though pork is widely consumed in many non-Muslim communities. In this study, the concentrations of heavy metals in different muscles and edible offal of consumed pork were determined and their related health risks were evaluated. This study will provide a significant reference to understand the quality and safety of pork in China or other similar developing countries.

9.
Int J Biol Macromol ; 142: 232-236, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669276

RESUMO

The antioxidant activities of polysaccharide from balsam pear were studied. It was determined by gel permeation chromatography that the molecular weight distribution of purified polysaccharide was concentrated near 33582 Da. It indicated that the monosaccharide components were rhamnose, galacturonic acid, galactose, xylose and arabinose. Fourier transform infrared spectroscopy, nuclear magnetic resonance and Congo red experiments showed that there are C1, C2, C3, C5 links, and stable ß-triple helix conformation in aqueous solution. It was found that polysaccharide had good scavenging effect on free radicals. So, balsam pear polysaccharide should be a potential antioxidant.

10.
J Sci Food Agric ; 100(5): 1971-1979, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31846079

RESUMO

BACKGROUND: Water absorption is the dominant factor affecting the quality deterioration of dried Lentinus edodes. We therefore analyzed the effect of moisture content and dynamic water status on physical properties of the mushroom stored at water activity (aw ), 0.33, 0.43, 0.67, 0.76, and 0.84 for 50 days. Moisture mobility and water status were analyzed using low-field nuclear magnetic resonance, while hardness and microstructure were determined as texture characteristics. Meanwhile, an electronic nose and headspace solid-phase micro-extraction combined with gas chromatography-mass spectrometry (HS-SPME-GC-MS) were used to analyze the flavor properties of dried L. edodes. RESULTS: The results showed that bound water was the dominant water status in dried L. edodes. The content and molecular mobility of bound water increased at aw = 0.67, 0.76, and 0.84. This contributed to discoloration, hardness loss, and microstructure sparsity of dried L. edodes. The increasing content and molecular mobility of bound water aggravated the deterioration of characteristic flavor by reducing acid, aldehyde, and ketone content. CONCLUSION: Unlike immobilized or free water, bound water had a critical influence on the quality deterioration of dried L. edodes during storage. © 2019 Society of Chemical Industry.


Assuntos
Cogumelos Shiitake/química , Água/química , Aldeídos/química , Aldeídos/isolamento & purificação , Nariz Eletrônico , Aromatizantes/química , Aromatizantes/isolamento & purificação , Armazenamento de Alimentos , Cromatografia Gasosa-Espectrometria de Massas , Cetonas/química , Cetonas/isolamento & purificação , Microextração em Fase Sólida
11.
Pediatr Blood Cancer ; 67(1): e28040, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31612640

RESUMO

BACKGROUND: Glucocorticoids and asparaginase, used to treat acute lymphoblastic leukemia (ALL), can cause hypertriglyceridemia. We compared triglyceride levels, risk factors, and associated toxicities in two ALL trials at St. Jude Children's Research Hospital with identical glucocorticoid regimens, but different asparaginase formulations. In Total XV (TXV), native Escherichia coli l-asparaginase was front-line therapy versus the pegylated formulation (PEG-asparaginase) in Total XVI (TXVI). PROCEDURE: Patients enrolled on TXV (n = 498) and TXVI (n = 598) were assigned to low-risk (LR) or standard/high-risk (SHR) treatment arms (ClinicalTrials.gov identifiers: NCT00137111 and NCT00549848). Triglycerides were measured four times and were evaluable in 925 patients (TXV: n = 362; TXVI: n = 563). The genetic contribution was assessed using a triglyceride polygenic risk score (triglyceride-PRS). Osteonecrosis, thrombosis, and pancreatitis were prospectively graded. RESULTS: The largest increase in triglycerides occurred in TXVI SHR patients treated with dexamethasone and PEG-asparaginase (4.5-fold increase; P <1 × 10-15 ). SHR patients treated with PEG-asparaginase (TXVI) had more severe hypertriglyceridemia (>1000 mg/dL) compared to native l-asparaginase (TXV): 10.5% versus 5.5%, respectively (P = .007). At week 7, triglycerides did not increase with dexamethasone treatment alone (LR patients) but did increase with dexamethasone plus asparaginase (SHR patients). The variability in triglycerides explained by the triglyceride-PRS was highest at baseline and declined with therapy. Hypertriglyceridemia was associated with osteonecrosis (P = .0006) and thrombosis (P = .005), but not pancreatitis (P = .4). CONCLUSION: Triglycerides were affected more by PEG-asparaginase than native l-asparaginase, by asparaginase more than dexamethasone, and by drug effects more than genetics. It is not clear whether triglycerides contribute to thrombosis and osteonecrosis or are biomarkers of the toxicities.


Assuntos
Asparaginase/efeitos adversos , Asparaginase/química , Composição de Medicamentos , Hipertrigliceridemia/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Hipertrigliceridemia/induzido quimicamente , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico
12.
Food Chem ; 309: 125702, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31685370

RESUMO

Our previous study indicated that nanocomposite packaging material (Nano-PM) containing nano-Ag, nano-TiO2, nano-SiO2 and nanoattapulgite alleviated postharvest senescence of Flammulina velutipes by regulating respiration and energy metabolism. In this study, extracellular ATP (eATP) and programmed cell death (PCD) were employed as critical factors to further investigate the senescence mechanism of postharvest F. velutipes. Results demonstrated that Nano-PM delayed apyrase activity decrease and stimulated critical oxidative phosphorylation-related gene expression to inhibit eATP content increase, which is a crucial signaling molecule related to delaying senescence. The regulation of eATP resulted in alleviating PCD including chromosomal concentration, DNA fragmentation, Ca2+ influx, high caspase-1 activity and cytochrome c content and leading to high cell viability. Overall, Nano-PM alleviated PCD and postharvest senescence of F. velutipes by regulating extracellular ATP.


Assuntos
Trifosfato de Adenosina/metabolismo , Apoptose , Flammulina/metabolismo , Embalagem de Alimentos/métodos , Nanocompostos/química , Apoptose/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Flammulina/efeitos dos fármacos , Nanocompostos/toxicidade , Óxido Nítrico/análise , Dióxido de Silício/química , Prata/química , Titânio/química
13.
Nat Commun ; 10(1): 5348, 2019 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767839

RESUMO

There is increasing evidence for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children. To identify new risk variants for B-cell ALL (B-ALL) we conducted a meta-analysis with four GWAS (genome-wide association studies), totalling 5321 cases and 16,666 controls of European descent. We herein describe novel risk loci for B-ALL at 9q21.31 (rs76925697, P = 2.11 × 10-8), for high-hyperdiploid ALL at 5q31.1 (rs886285, P = 1.56 × 10-8) and 6p21.31 (rs210143 in BAK1, P = 2.21 × 10-8), and ETV6-RUNX1 ALL at 17q21.32 (rs10853104 in IGF2BP1, P = 1.82 × 10-8). Particularly notable are the pleiotropic effects of the BAK1 variant on multiple haematological malignancies and specific effects of IGF2BP1 on ETV6-RUNX1 ALL evidenced by both germline and somatic genomic analyses. Integration of GWAS signals with transcriptomic/epigenomic profiling and 3D chromatin interaction data for these leukaemia risk loci suggests deregulation of B-cell development and the cell cycle as central mechanisms governing genetic susceptibility to ALL.

14.
Food Sci Nutr ; 7(9): 3006-3016, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31572594

RESUMO

A number of 17 sulfonamides (SNs) determination in porcine tissues using two new materials including Enhanced Matrix Removal for Lipid (EMR-L) and Oasis PRiME hydrophilic-lipophilic balance (HLB), and the conventional liquid-liquid extraction with n-hexane (LLE) sample preparation methods were evaluated and compared. Samples were extracted uniformly with acidified acetonitrile and cleaned up by the three sample preparation methods, and then, analytes were further separated by ultrahigh-performance liquid chromatography (UHPLC) and detected by a triple quadrupole mass spectrometry (MS/MS) or a quadrupole-time-of-flight tandem mass spectrometry (Q-TOF/MS). The results showed that the matrix effects from the EMR-L and HLB were significantly lower than that from LLE, suggesting that these two new materials are superior to n-hexane in the precipitation of proteins and the adsorption of lipids. Moreover, the recoveries of 17 SNs were quantified by the matrix-matched calibration curve at spiked level of 5, 10, and 20 µg/kg, and 97.0% of the results satisfied method validation requirements. The samples cleaned up by EMR-L and HLB achieved the highest average recovery in liver and kidney with high moisture content, and muscle which is high in fat, respectively. In addition, Q-TOF/MS could play a good role in aided verification based on the result of repeated validation test. In summary, either combination of approaches could be used to achieve monitoring purposes; it is still worthwhile to adopt a specific sample preparation method and MS detector for the quantification in a specific matrix.

15.
Food Chem Toxicol ; 134: 110833, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31574266

RESUMO

Flavor deterioration is a serious problem in dried carrots during storage and is frequently accompanied by water absorption and bacterial growth. To explore the underlying mechanism of flavor deterioration, relationship among water status, exogenous bacterial composition and flavor changes in dried carrots were analyzed at different water activities (aw, 0.43, 0.67, 0.76 and 0.84). Results suggested that the water molecules mobility significantly increased in the dried carrots at higher aw levels (0.67, 0.76 and 0.84), this was attributed to the raised content of bound water, rather than immobilized or free water. Consequently, this accelerated microbial growth and flavor deterioration. At aw = 0.84, the characteristic flavor compounds including 2,3-butanediol, pentanoic acid, hexanoic acid, heptanoic acid and nonanoic acid were lost. The disagreeable flavor compounds including terpenes were produced during the storage period. These were the main contributors of flavor deterioration in the dried carrots. Lactic acid bacteria, as the dominant bacteria in dried carrots during storage, were proved to be closely related to the production of o-cymene, ß-pinene and ß-myrcene. Moreover, the emergence of Pediococcus spp. was the major factor leading to the increase of γ-terpinene in dried carrots.


Assuntos
Daucus carota/microbiologia , Conservação de Alimentos , Paladar , /metabolismo , Alcenos/metabolismo , /metabolismo , Lactobacillales/metabolismo , Água/química
16.
Inflammation ; 42(6): 2170-2180, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31494795

RESUMO

Sepsis-induced myocardial dysfunction (SIMD), lack of effective treatment, accounts for high mortality of sepsis. Mitochondrion-targeted antioxidant peptide SS31 has been revealed to be responsible for certain cardiovascular disease by ameliorating oxidative stress injury. But whether it protects a septic heart remains little known. This study sought to prove that SS31 was capable of improving sepsis-induced myocardial dysfunction dramatically. C57BL/6 mice were intraperitoneally administered lipopolysaccharide (LPS), exposed to systemic inflammation. Thirty-five C57BL/6 mice were randomly divided into four groups: sham group, LPS group (5 mg/kg), SS31 group (5 mg/kg), and SS31 + LPS group (treatment group). Heart tissues were harvested for pathological examination at the indicated time points. H9C2 cell were treated with LPS with or without the presence of SS31 (10 µM) at 37 °C to assess the effect on cardiomyocytes at the indicated time points. SS31 restored myocardial morphological damage and suppressed inflammatory response as evidenced by significantly decreasing the mRNA levels of IL-6, IL-1ß, and TNF-α in vitro and in vivo. In addition, myocardial energy deficiency secondary to sepsis was remarkedly ameliorated by SS31. Furthermore, we found that SS-31 normalized the activity of malondialdehyde, glutathione peroxidase, and superoxide dismutase in vitro and in vivo, and maintained mitochondrial membrane potential (MMP) as well. And western blot was applied to measure the expressions of p-p38MAPK, p-JNK1/2, p-ERK, p62, and NF-κB p65; the results illuminated that the cardioprotective effect of SS31 was partly linked to NF-κB. In conclusion, SS31 therapy effectively protected the heart against LPS-induced cardiac damage.

17.
Carbohydr Polym ; 225: 115238, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521271

RESUMO

Four phenolic acid-grafted-chitosan conjugates were prepared with different phenolic acids including gallic acid (GLA), caffeic acid (CA), gentisate acid (GTA) and sinapic acid (SA), and their characteristics were analyzed. Furthermore, the antioxidant and antimicrobial activities of conjugates were compared to screen out the optimal conjugates. The characterization analysis showed that the UV absorption peaks of CA-g-CS were stronger than that of GLA-g-CS, indicating a higher substitution degree. In addition, the substitution degree and antioxidant activity of caffeic acid-grafted-chitosan (CA-g-CS) and gallic acid-grafted-chitosan (GLA-g-CS) had significantly (p < 0.05) higher than CS and other two conjugates. However, CA-g-CS demonstrated stronger bacteriostatic ability, of which the minimum inhibitory concentrations (MICs) against Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis and Staphylococcus aureus were lower, and the inhibitory zones were larger than GLA-g-CS. In summary, the present findings will provide a theoretical basis for the expanding of CS application in food processing and preservation.


Assuntos
Anti-Infecciosos/química , Antioxidantes/química , Quitosana/química , Hidroxibenzoatos/química , Anti-Infecciosos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Manipulação de Alimentos , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
18.
Blood ; 134(15): 1227-1237, 2019 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-31350265

RESUMO

Children with Down syndrome (DS) have a 20-fold increased risk of acute lymphoblastic leukemia (ALL) and distinct somatic features, including CRLF2 rearrangement in ∼50% of cases; however, the role of inherited genetic variation in DS-ALL susceptibility is unknown. We report the first genome-wide association study of DS-ALL, comprising a meta-analysis of 4 independent studies, with 542 DS-ALL cases and 1192 DS controls. We identified 4 susceptibility loci at genome-wide significance: rs58923657 near IKZF1 (odds ratio [OR], 2.02; Pmeta = 5.32 × 10-15), rs3731249 in CDKN2A (OR, 3.63; Pmeta = 3.91 × 10-10), rs7090445 in ARID5B (OR, 1.60; Pmeta = 8.44 × 10-9), and rs3781093 in GATA3 (OR, 1.73; Pmeta = 2.89 × 10-8). We performed DS-ALL vs non-DS ALL case-case analyses, comparing risk allele frequencies at these and other established susceptibility loci (BMI1, PIP4K2A, and CEBPE) and found significant association with DS status for CDKN2A (OR, 1.58; Pmeta = 4.1 × 10-4). This association was maintained in separate regression models, both adjusting for and stratifying on CRLF2 overexpression and other molecular subgroups, indicating an increased penetrance of CDKN2A risk alleles in children with DS. Finally, we investigated functional significance of the IKZF1 risk locus, and demonstrated mapping to a B-cell super-enhancer, and risk allele association with decreased enhancer activity and differential protein binding. IKZF1 knockdown resulted in significantly higher proliferation in DS than non-DS lymphoblastoid cell lines. Our findings demonstrate a higher penetrance of the CDKN2A risk locus in DS and serve as a basis for further biological insights into DS-ALL etiology.


Assuntos
Síndrome de Down/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Criança , Inibidor p16 de Quinase Dependente de Ciclina/genética , Proteínas de Ligação a DNA/genética , Síndrome de Down/complicações , Fator de Transcrição GATA3/genética , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Fator de Transcrição Ikaros/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Fatores de Transcrição/genética
19.
J Agric Food Chem ; 67(32): 8773-8782, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31283205

RESUMO

Conquering rapid postripeness and deterioration of Agaricus bisporus is quite challenging. We previously observed that methyl jasmonate (MeJA) pretreatment postponed the deterioration of A. bisporus, but the mechanism is unknown. Here, a nontargeted metabolomics analysis by ultrahigh-pressure liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) revealed that MeJA increased the synthesis of malate by inhibiting the decomposition of fumarate and cis-aconitate. MeJA maintained energy supply by enhancing ATP content and energy charge level and improving hexokinase and glucose-6-phosphate dehydrogenase activities as well. These results promoted ATP supply by maintaining glycolysis, the TCA cycle, and the pentose phosphate pathway. In addition, we revealed that the delayed deterioration was attributed to MeJA treatment which stimulated the energy status of A. bisporus by reducing the respiration rate and nutrient decomposition, thus maintaining energy production. Our results provide a new insight into the role of MeJA treatment in delaying deterioration of A. bisporus through ATP production and supply.


Assuntos
Acetatos/farmacologia , Agaricus/efeitos dos fármacos , Agaricus/metabolismo , Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Ácido Aconítico/metabolismo , Trifosfato de Adenosina/metabolismo , Agaricus/química , Agaricus/crescimento & desenvolvimento , Cromatografia Líquida de Alta Pressão/métodos , Metabolismo Energético/efeitos dos fármacos , Fumaratos/metabolismo , Malatos/metabolismo , Metabolômica , Espectrometria de Massas em Tandem/métodos
20.
J Clin Oncol ; 37(23): 2051-2061, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31188727

RESUMO

PURPOSE: Pegaspargase (PEG-ASP) has largely replaced native Escherichia coli asparaginase (L-ASP) in the treatment of acute lymphoblastic leukemia because of its longer half-life and lower immunogenicity. Risk factors for allergic reactions to PEG-ASP remain unclear. Here, we identify risk factors for reactions in a front-line acute lymphoblastic leukemia trial and assess the usefulness of serum antibodies for diagnosing allergy and predicting rechallenge outcome. PATIENTS AND METHODS: PEG-ASP was administered to 598 patients in St Jude's Total XVI study. Results were compared with Total XV study (ClinicalTrials.gov identifiers: NCT00549848 and NCT00137111), which used native L-ASP. Serum samples (n = 5,369) were analyzed for anti-PEG-ASP immunoglobulin G by enzyme-linked immunosorbent assay. Positive samples were tested for anti-polyethylene glycol (PEG) and anti-L-ASP. We analyzed potential risk factors for reactions and associations between antibodies and reactions, rechallenge outcomes, and PEG-ASP pharmacokinetics. RESULTS: Grade 2 to 4 reactions were less common in the Total XVI study with PEG-ASP (81 [13.5%] of 598) than in the Total XV study with L-ASP (169 [41.2%] of 410; P = 1.4 × 10-23). For Total XVI, anti-PEG, not anti-L-ASP, was the predominant component of anti-PEG-ASP antibodies (96%). In a multivariable analysis, more intrathecal therapy (IT) predicted fewer reactions (P = 2.4 × 10-5), which is consistent with an immunosuppressant contribution of IT. Anti-PEG-ASP was associated with accelerated drug clearance (P = 5.0 × 10-6). Failure of rechallenge after initial reactions was associated with anti-PEG-ASP (P = .0078) and was predicted by the occurrence of angioedema with first reaction (P = .01). CONCLUSION: Less IT therapy was the only independent clinical risk factor for reactions to PEG-ASP. PEG, and not L-ASP, is the major antigen that causes allergic reactions. Anti-PEG-ASP has utility in predicting and confirming clinical reactions to PEG-ASP as well as in identifying patients who are most likely to experience failure with rechallenge.

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