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1.
Food Funct ; 12(19): 9391-9404, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606557

RESUMO

Cisplatin is one of the most effective chemotherapeutic agents used for the treatment of a wide variety of cancers. However, cisplatin has been associated with nephrotoxicity, which limits its application in clinical treatment. Various studies have indicated the protective effect of phospholipids against acute kidney injury. However, no study has focused on the different effects of phospholipids with different fatty acids on cisplatin-induced nephrotoxicity and on the combined effects of phospholipids and cisplatin in tumour-bearing mice. In the present study, the potential renoprotective effects of phospholipids with different fatty acids against cisplatin-induced nephrotoxicity were investigated by determining the serum biochemical index, renal histopathological changes, protein expression level and oxidative stress. The results showed that docosahexaenoic acid-enriched phospholipids (DHA-PL) and eicosapentaenoic acid-enriched phospholipids (EPA-PL) could alleviate cisplatin-induced nephrotoxicity by regulating the caspase signaling pathway, the SIRT1/PGC1α pathway, and the MAPK (mitogen-activated protein kinase) signaling pathway and by inhibiting oxidative stress. In particular, DHA-PL exhibited a better inhibitory effect on oxidative stress and apoptosis compared to EPA-PL. Furthermore, DHA-PL exhibited an additional effect with cisplatin on the survival of ascitic tumor-bearing mice. These findings suggested that DHA-PL are one kind of promising supplement for the alleviation of cisplatin-induced nephrotoxicity without compromising its antitumor activity.

2.
Mar Drugs ; 19(9)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34564161

RESUMO

Prevention of acute kidney injury caused by drugs is still a clinical problem to be solved urgently. Astaxanthin (AST) and docosahexaenoic acid (DHA) are important marine-derived active ingredients, and they are reported to exhibit renal protective activity. It is noteworthy that the existing forms of AST in nature are mainly fatty acid-acylated AST monoesters and diesters, as well as unesterified AST, in which DHA is an esterified fatty acid. However, no reports focus on the different bioactivities of unesterified AST, monoesters and diesters, as well as the recombination of DHA and unesterified AST on nephrotoxicity. In the present study, vancomycin-treated mice were used to evaluate the effects of DHA-acylated AST monoesters, DHA-acylated AST diesters, unesterified AST, and the recombination of AST and DHA in alleviating nephrotoxicity by determining serum biochemical index, histopathological changes, and the enzyme activity related to oxidative stress. Results found that the intervention of DHA-acylated AST diesters significantly ameliorated kidney dysfunction by decreasing the levels of urea nitrogen and creatinine, alleviating pathological damage and oxidative stress compared to AST monoester, unesterified AST, and the recombination of AST and DHA. Further studies revealed that dietary DHA-acylated AST esters could inhibit the activation of the caspase cascade and MAPKs signaling pathway, and reduce the levels of pro-inflammatory cytokines. These findings indicated that the administration of DHA-acylated AST esters could alleviate vancomycin-induced nephrotoxicity, which represented a potentially novel candidate or therapeutic adjuvant for alleviating acute kidney injury.

3.
Front Oncol ; 11: 706935, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485141

RESUMO

Background: Approximately 30% of Chinese individuals with cytogenetically normal acute myeloid leukemia (CN-AML) have biallelic CEBPA (biCEBPA) mutations. The prognosis and optimal therapy for these patients are controversial in clinical practice. Methods: In this study, we performed targeted region sequencing of 236 genes in 158 individuals with this genotype and constructed a nomogram model based on leukemia-free survival (LFS). Patients were randomly assigned to a training cohort (N =111) and a validation cohort (N =47) at a ratio of 7:3. Risk stratification was performed by the prognostic factors to investigate the risk-adapted post-remission therapy by Kaplan-Meier method. Results: At least 1 mutated gene other than CEBPA was identified in patients and mutation number was associated with LFS (61.6% vs. 39.0%, P =0.033), survival (85.6% vs. 62.9%, P =0.030) and cumulative incidence of relapse (CIR) (38.4% vs. 59.5%, P =0.0496). White blood cell count, mutations in CFS3R, KMT2A and DNA methylation related genes were weighted to construct a nomogram model and differentiate two risk subgroups. Regarding LFS, low-risk patients were superior to the high-risk (89.3% vs. 33.8%, P <0.001 in training cohort; 87.5% vs. 18.2%, P =0.009 in validation cohort). Compared with chemotherapy, allogenic hematopoietic stem cell transplantation (allo-HSCT) improved 5-year LFS (89.6% vs. 32.6%, P <0.001), survival (96.9% vs. 63.6%, P =0.001) and CIR (7.2% vs. 65.8%, P <0.001) in high-risk patients but not low-risk patients (LFS, 77.4% vs. 88.9%, P =0.424; survival, 83.9% vs. 95.5%, P =0.173; CIR, 11.7% vs. 11.1%, P =0.901). Conclusions: Our study indicated that biCEBPA mutant-positive CN-AML patients could be further classified into two risk subgroups by four factors and allo-HSCT should be recommended for high-risk patients as post-remission therapy. These data will help physicians refine treatment decision-making in biCEBPA mutant-positive CN-AML patients.

4.
Mol Nutr Food Res ; 65(20): e2100339, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34378848

RESUMO

INTRODUCTION: Malnutrition in early life affects the growth and development of fetus and children, which has a long-term impact on adult health. Previous studies reveal a relationship between dietary omega-3 polyunsaturated fatty acid (n-3 PUFA) content, brain development, and the prevalence of neurodevelopmental disorders and inflammation. However, it is unclear about the effect of n-3 PUFA-deficiency in early life on the development of Parkinson's disease (PD) in old age, as well as the neuroprotective effect of DHA- and EPA-enriched phospholipids (DHA/EPA-PLs) supplemented in old age in long-term n-3 PUFA-deficient mice. METHODS AND RESULTS: The PD mice induced by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in n-3 PUFA-adequate (N) and -deficient (DEF) group are supplemented with a DHA/EPA-PLs diet for 2 weeks (N+DPL, DEF+DPL). DHA/EPA-PLs supplementation significantly protects against MPTP-induced impairments. The DEF+DPL group shows poorer motor performance, the loss of dopaminergic neurons, mitochondrial dysfunction, and neurodevelopment delay than the N+DPL group, and still did not recover to the Control level. CONCLUSIONS: Dietary n-3 PUFA-deficiency in early life exhibits more aggravated MPTP-induced neurotoxicity in old age, than DHA/EPA-PLs supplementation recovers brain DHA levels and exerts neuroprotective effects in old age in long-term n-3 PUFA-deficient mice, which might provide a potential dietary guidance.

5.
Biosci Biotechnol Biochem ; 85(8): 1873-1884, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34196365

RESUMO

Phospholipids reportedly alleviate drug-induced acute kidney injury. However, no study has compared the effect of phospholipids with different fatty acids and polar heads on drug-induced nephrotoxicity. In the present study, we aimed to compare the possible nephroprotection afforded by phosphatidylcholine and phosphatidylserine with different fatty acids in a mouse model of vancomycin-induced nephrotoxicity. Pretreatment with phospholipids rich in docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) doubled the survival time when compared with the model group. Moreover, phospholipids rich in DHA/EPA significantly reduced the serum levels of renal function biomarkers and ameliorated kidney pathologies. In terms of alleviating renal damage, no significant differences were observed between different polar heads in DHA-enriched phospholipids, while phosphatidylserine from soybean was better than phosphatidylcholine in mitigating renal injury. Furthermore, DHA/EPA-enriched phospholipids inhibited vancomycin-induced nephrotoxicity mainly by inhibiting apoptosis and oxidative stress. These results provide a scientific basis for phospholipids as potential ingredients to prevent acute kidney injury.


Assuntos
Antibacterianos/toxicidade , Ácidos Graxos/farmacologia , Rim/efeitos dos fármacos , Fosfatidilcolinas/farmacologia , Fosfatidilserinas/farmacologia , Vancomicina/toxicidade , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Ácidos Graxos/metabolismo , Rim/citologia , Rim/metabolismo , Rim/fisiopatologia , Sistema de Sinalização das MAP Quinases , Camundongos , Mitocôndrias/metabolismo , Análise de Sobrevida
6.
Mol Nutr Food Res ; 65(17): e2100009, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34219360

RESUMO

SCOPE: A growing number of studies have reported the effects of eicosapentaenoic acid (EPA) and terrestrial phospholipids on ameliorating mood disorders. Marine-derived EPA-enriched phospholipids (EPA-PL) exhibit the structural characteristics of EPA and phospholipids. However, the effect of dietary EPA-PL, and the differences between amphiphilic EPA-PL and lyophobic EPA on mood disorders had not been studied. METHODS AND RESULTS: A comparative investigation to determine the effects of dietary EPA-enriched ethyl ester (EPA-EE) and EPA-PL on improving depression- and anxiety-like behavior in a mouse model is performed, induced by 4 week chronic unpredictable mild stress (CUMS) coupled with lipopolysaccharide (LPS) challenge. It is found that dietary 4 week 0.6% (w/w) EPA-PL rescued depression- and anxiety-like behavior to a greater extent than did EPA-EE. Moreover, dietary EPA-PL significantly reduced the immobility time by 56.6%, close to the normal level, in forced swimming test, which revealed a reversal of depression-like behavior. Further studies revealed that dietary EPA-PL regulated immunity, monoamine systems, and the hypothalamic-pituitary-adrenal (HPA) axis by multi-target interactions, including inhibition of neuroinflammation and apoptosis. CONCLUSION: EPA-PL exerted superior effects to EPA-EE in alleviating depression- and anxiety-like behavior. The data suggest potential novel candidate or targeted dietary patterns to prevent and treat mood disorder.

8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 181-187, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554816

RESUMO

OBJECTIVE: To deeply understand the clinical manifestation, laboratory examination characteristics, diagnosis and treatment of an eight p11 myeloproliferative syndrome (EMS) with rare phenotypes. METHODS: The clinical and laboratory characteristics and the process of allogeneic hematopoietic stem cell transplantation (allo-HSCT) were summarized in 1 rare EMS case involving T/B/myeloid cells. Meanwhile, 2 similar cases in the previous literature were also discussed. RESULTS: The bone marrow examination indicated that the patient with B-cell acute lymphocytic leukemia. The lymph node biopsy showed that the patient was T lymphoblastic/myeloid lymphoma. The 8p11 abnormality was found by the examination of bone marrow chromosomes. The RT-PCR examination showed that the BCR-ABL fused gene was negtive. The FGFR1 breakage was found by using the FISH with FGFR1 probe in lymph node. The Mutation of FMNL3, NBPF1 and RUNX1 genes was found by using the whole exome sequencing. The patient received allo-HSCT under CR2. By the follow-up till to September 2019, the patient survived without the above-mentioned disease. CONCLUSION: EMS manifest as neoplasms involving T-lineage, B-lineage, and myeloid-lineage simultaneously is extremely rare. Although the FGFR1 gene-targeted therapy can be conducted, allo-HSCT should be actively considered.


Assuntos
Neoplasias Hematológicas , Transtornos Mieloproliferativos , Medula Óssea , Cromossomos Humanos Par 8 , Forminas , Humanos , Transtornos Mieloproliferativos/genética , Fenótipo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Translocação Genética
9.
Food Chem ; 346: 128958, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33418418

RESUMO

The enrichment and transformation of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) enriched phospholipids for eggs deserve attention. The aim of the present study was to elucidate the comparative effects of DHA and EPA enriched phospholipids and triacylglycerols on egg fortification by determining the fatty acid composition of egg yolk after intervention with fish oil (15 g/kg) and krill oil (15 and 30 g/kg) for three consecutive weeks. The results indicated that laying hens could incorporate over 300 mg DHA and EPA into one egg. Greater retention efficiency of DHA and EPA in eggs was observed in fish oil supplementation compared with krill oil at equivalent dietary levels. DHA and EPA were prone to locate at the sn-2 position of phosphatidylcholine. Consequently, fish oil possessed high DHA content and conversion rate, and krill oil could raise the proportion of DHA-containing phospholipids in eggs.


Assuntos
Dieta/veterinária , Ácidos Docosa-Hexaenoicos/análise , Ovos/análise , Ácido Eicosapentaenoico/análise , Animais , Galinhas , Cromatografia Gasosa , Suplementos Nutricionais , Gema de Ovo/química , Ácidos Graxos/análise , Ácidos Graxos/química , Óleos de Peixe/administração & dosagem
10.
J Nutr Biochem ; 89: 108578, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33388352

RESUMO

The maternal nutritional status during pregnancy and lactation was closely related to the growth and development of the fetus and infants, which had a profound impact on the health of the offspring. N-3 polyunsaturated fatty acid (PUFA) had been proved to have beneficial effects on glucolipid metabolism. However, the effects of dietary different n-3 PUFA levels for mother during pregnancy and lactation on susceptibility to high-fat-diet-induced metabolic syndrome for offspring in adulthood are still unclear. The maternal mice were fed with control, n-3 PUFA-deficient or fish oil-contained n-3 PUFA-rich diets during pregnancy and lactation, and the weaned offspring were fed with high-fat or low-fat diet for 13 weeks, then were subjected to oral glucose tolerance tests. The results showed that dietary n-3 PUFA-deficiency in early life could aggravate the high-fat-diet-induced glucolipid metabolism disorders, including glucose intolerance, insulin resistance, obesity, and dyslipidemia, thus increased the susceptibility to metabolic syndrome of adult mice. Notably, nutritional supplementation with n-3 PUFA in early life could significantly alleviate the glucose metabolism disorders by increasing insulin sensitivity, inhibiting gluconeogenesis and promoting glycogenesis. In addition, administration with n-3 PUFA in early life remarkably reduced serum and hepatic lipid profiles by mediating the expression of genes related to lipogenesis and ß-oxidation of fatty acids. Dietary n-3 PUFA-deficiency in early life increases the susceptibility to metabolic syndrome of adult offspring, and nutritional supplementation with n-3 PUFA enhances the tolerance to a high-fat diet of adult offspring.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos Ômega-3/farmacologia , Fenômenos Fisiológicos da Nutrição Materna , Síndrome Metabólica/prevenção & controle , Animais , Dieta com Restrição de Gorduras , Suplementos Nutricionais , Dislipidemias/etiologia , Dislipidemias/prevenção & controle , Feminino , Óleos de Peixe/farmacologia , Intolerância à Glucose/metabolismo , Teste de Tolerância a Glucose , Resistência à Insulina , Lactação/metabolismo , Metabolismo dos Lipídeos , Lipídeos/sangue , Lipogênese , Fígado/metabolismo , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/patologia , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/prevenção & controle , Gravidez
11.
World J Clin Cases ; 8(22): 5618-5624, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33344552

RESUMO

BACKGROUND: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by recurrent mutations in the JAK2, CALR, and MPL genes. The CALR and MPL co-mutation is very rare. To our knowledge, no more than five cases have been reported. Here, we report a case of PMF in which a CALR and MPL co-mutation was detected by next-generation sequencing (NGS) technology, and a literature review was performed. CASE SUMMARY: A 73-year-old woman was admitted to our hospital in 2018 due to abdominal distension. The patient had splenomegaly, lymphadenopathy, leukopenia, anemia, and immature granulocytes in peripheral blood. There were dacrocytes and atypical megakaryocytes in bone marrow, and megakaryocytic proliferation was very active, accompanied by reticulin fibrosis grade 2. By NGS analysis of the bone marrow sample, we detected mutations in CALR, MPL, and PIK3RI, while JAK2 V617F and BCR-ABL were negative. Therefore, the patient was diagnosed with PMF and received oral ruxolitinib. However, the spleen and hematologic responses were poor. We review the literature, analyze previous reports of the mutation sites in our patient and differences between our patient and other reported cases of co-mutated CALR and MPL genes, and discuss the reason why the CALR and MPL co-mutations are rare and possible mechanisms and their impact on the prognosis of patients. CONCLUSION: CALR and MPL mutations can be concurrent in MPN, but they are rare. The use of NGS may help to identify more patients with co-mutated CALR and MPL genes. This will help to further explore the mechanism and its impact on these patients to develop appropriate treatment strategies.

12.
Chem Biodivers ; 17(11): e2000706, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33026163

RESUMO

Three new ß-triketone flavanone hybrids, cajuputones A-C were obtained from Melaleuca cajuputi (the Australian 'tea tree'). The structures of cajuputones A-C were elucidated by 1D/2D NMR spectroscopy and HR-ESI-MS analyses; and their absolute configurations were established by electric circular dichroism (ECD) calculations using TDDFT method. Structurally, cajuputones A-C feature a rare 6/6/6/6 oxatetracyclic ring system fused between an acylphloroglucinol-derived ß-triketone and a pinocembrin or strobopinin moiety via an angle-type pyran-like motif. DFT-based conformational optimization in chloroform explained the similarity of the 1D NMR data of cajuputones B and C (C-2 epimers).


Assuntos
Flavanonas/química , Melaleuca/química , Dicroísmo Circular , Flavanonas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Melaleuca/metabolismo , Conformação Molecular , Folhas de Planta/química , Folhas de Planta/metabolismo , Caules de Planta/química , Caules de Planta/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Estereoisomerismo
13.
Pharmacol Res ; 160: 105191, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32911073

RESUMO

Sea cucumbers are widely consumed in traditional medicine and food. Sea cucumbers-derived sulfated sterol exhibits a sulfate group at C-3 position, which is different from phytosterol with a hydroxyl group. However, the effect of sterol sulfate on metabolic syndrome remains unknown. The purpose of the present study is to investigate the alleviation of sterol sulfate on high-fat-high-fructose diet (HFFD)-induced insulin resistance and inflammation. After 2 weeks feeding with HFFD, male C57BL/6J mice were continuously fed with HFFD plus 0.4 % (w/w) sterol sulfate or phytosterol for 6 weeks. The OGTT was carried out at 7 weeks. At the end of the experimental period, the changes of glycogen, circulating glucose, insulin, pro-inflammatory cytokine and adiponectin were measured. H&E staining was used to observe the morphological changes in adipose tissue. Furthermore, the underlying molecular mechanisms were investigated. Dietary sterol sulfate was superior to phytosterol in reducing body weight gain, adipocyte hypertrophy, and levels of circulating glucose and insulin, as well as increasing the glycogen content of tissues. Furthermore, sterol sulfate ameliorated insulin resistance mainly due to the inhibition of gluconeogenesis, the promotion of glycogen synthesis and GLUT4 translocation by activating PI3K/Akt signaling pathway. Additionally, sterol sulfate effectively attenuated inflammation by increasing serum adiponectin and reducing pro-inflammatory cytokine release. Sterol sulfate exhibited a more significant effect than phytosterol in alleviating HFFD -induced insulin resistance and inflammation, which might be closely related to the sulfate group. The results might provide insights into the prevention and alleviation of metabolic syndrome.


Assuntos
Anti-Inflamatórios/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Frutose/efeitos adversos , Inflamação/tratamento farmacológico , Resistência à Insulina , Obesidade/tratamento farmacológico , Pepinos-do-Mar/química , Esteróis/uso terapêutico , Adiponectina/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Citocinas/metabolismo , Teste de Tolerância a Glucose , Glicogênio/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/complicações , Transdução de Sinais/efeitos dos fármacos
14.
Food Funct ; 11(9): 8038-8050, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32845953

RESUMO

Non-esterified astaxanthin (AST) has been reported to exhibit protective effects from Parkinson's disease (PD). Notably, DHA-acylated astaxanthin ester (DHA-AST) is widely distributed in the seafood. However, whether DHA-AST has an effect on PD, and the differences between DHA-AST, non-esterified AST and the combination of non-esterified AST (AST) with DHA (DHA + AST) is unclear. In the present study, mice with PD, induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), were employed to investigate the effects of DHA-AST, AST and DHA + AST on Parkinson's disease. The rotarod test results showed that DHA-AST significantly suppressed the PD development in MPTP-induced mice, and was better than the effects of AST and DHA + AST. Further mechanistic studies indicated that all three astaxanthin supplements could inhibit oxidative stress in the brain. It was noted that DHA-AST had the best ability to suppress the apoptosis of dopaminergic neurons via the mitochondria-mediated pathway and JNK and P38 MAPK pathway in the brain among the three treated groups. DHA-AST was superior to AST in preventing behavioral deficits coupled with apoptosis rather than oxidative stress, and might provide a valuable reference for the prevention and treatment of neurodegenerative diseases.


Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/efeitos adversos , Apoptose/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/farmacologia , Ésteres/química , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Xantofilas/farmacologia , Animais , Encéfalo , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/química , Neurônios Dopaminérgicos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Xantofilas/química
15.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(3): 411-415, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32543152

RESUMO

Objective: To evaluate the diagnostic value of abnormal prothrombin (DCP) in Alpha-fetoproteins (AFP)-negative (AFP≤20 ng/mL) hepatocellular carcinoma and the relationship between DCP level and Child-Pugh grade, tumor size, TNM stage as well as differentiation. Methods: The inpatients diagnosed with hepatitis B-related liver disease were collected from June 2016 to December 2017, The diagnostic efficacy of DCP for AFP-negative HCC was analyzed by ROC. Area under the curve ( AUC), the best cut point, sensitivity, specificity, positive predictive value and negative predictive value were calculated. The relationship between DCP levels and the clinical characteristic of HCC was analyzed. Results: A total of 459 hepatitis B markers positive patients were included, including 136 cases of hepatocellular carcinoma, 173 cases of hepatitis B cirrhosis and 150 cases of chronic hepatitis B. DCP in AFP-negative hepatocellular carcinoma group was significantly higher than that in non-HCC group (CHB and LC) ( P<0.05). The AUC of DCP was 0.858, P<0.05. The optimal cut-off point for the diagnosis of hepatocellular carcinoma was 61 mAU/mL. The corresponding sensitivity, specificity, positive predictive value and negative predictive value were 72.8%, 88.2%, 61.1% and 89.7%, respectively. In different size of hepatocellular carcinoma, DCP level of those with diameter>3 cm was significantly higher than those with diameter≤3 cm ( P<0.05). In different TNM stages, DCP level in stage Ⅱ and Ⅲ was significantly higher than that in stage Ⅰ ( P<0.05). There was no significant difference of DCP level among different Child-Pugh grades and differentiation ( P>0.05). Conclusion: DCP has diagnostic value for AFP-negative hepatocellular carcinoma, its level may reflects the degree of tumor progression.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Protrombina , Biomarcadores , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Criança , Vírus da Hepatite B , Humanos , Neoplasias Hepáticas/diagnóstico , Precursores de Proteínas , Protrombina/metabolismo , Curva ROC , alfa-Fetoproteínas
16.
Zhongguo Zhong Yao Za Zhi ; 45(3): 584-595, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237517

RESUMO

A method was established for simultaneous determination of 21 active constituents including flavanols, isoflavones, flavonols, dihydroflavones, dihydroflavonols, chalcones, pterocarpan, anthocyanidins and phenolic acids in Spatholobi Caulis by ultra fast liquid chromatography with triple quadrupole linear ion trap mass spectrometry(UFLC-QTRAP-MS/MS). Then, it was employed to analyze and evaluate the dynamic accumulation of multiple bioactive constituents in Spatholobi Caulis. The chromatographic separation was performed on a XBridge®C_(18)(4.6 mm×100 mm, 3.5 µm) at 30 ℃ with a gradient elution of 0.3% formic acid aqueous solution-methanol, and the flow rate was 0.8 mL·min~(-1), using multiple-reaction monitoring(MRM) mode. A comprehensive evaluation of the multiple bioactive constituents was carried out by gray correlation analysis(GRA). The 21 target components showed good linearity(r>0.999 0) in the range of the tested concentrations. The average recovery rates of the 21 components were from 97.46% to 103.6% with relative standard deviations less than 5.0%. There were differences in the contents of 21 components in Spatholobi Caulis at diffe-rent harvest periods. Spatholobi Caulis had high quality from early November to early December, which is consistent with the local tradi-tional harvest period. This study reveals the rule of the dynamic accumulation of 21 components in Spatholobi Caulis and provides basic information for the suitable harvest time. At the same time, it provides a new method reference for the comprehensive evaluation of the internal quality of Spatholobi Caulis.


Assuntos
Fabaceae/química , Compostos Fitoquímicos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Caules de Planta/química , Plantas Medicinais/química , Espectrometria de Massas em Tandem
17.
J Agric Food Chem ; 68(19): 5339-5348, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32306729

RESUMO

Eicosapentaenoic acid (EPA)-enriched phosphoethanolamine plasmalogens (EPA-PlsEtns) might be retained in the intestine rich in gut microbiota for a long time after treatment. It reminded us that EPA-PlsEtns might affect intestinal microbiota composition and its metabolites, which have been identified as a contributing factor in the development of cardiovascular diseases. In the present study, EPA-PlsEtn administration for 8 weeks significantly reduced the atherosclerotic lesion area in low-density lipoprotein receptor deficient (LDLR-/-) mice. Notably, the serum total cholesterol and low-density lipoprotein cholesterol levels were significantly reduced by 33.6 and 38.2%, respectively, by EPA-PlsEtns instead of EPA in the form of ethyl ester (EPA-EE) treatment compared with the model group. EPA-PlsEtn administration also increased total neutral sterol and bile acids in feces by 92 and 39%, respectively, rather than EPA-EE. Mechanistically, EPA-PlsEtns might affect the abundance of gut microbiota contributing to the alteration of bile acid profiles, which might further accelerate bile acid synthesis via increasing cholesterol 7 α-hydroxylase expression induced by the inhibition of farnesoid X receptor activation.


Assuntos
Aterosclerose/tratamento farmacológico , Ácidos e Sais Biliares/metabolismo , Ácido Eicosapentaenoico/administração & dosagem , Etanolaminas/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Plasmalogênios/administração & dosagem , Receptores de LDL/genética , Animais , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/microbiologia , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Etanolaminas/análise , Humanos , Masculino , Camundongos , Camundongos Knockout , Plasmalogênios/análise , Receptores de LDL/metabolismo
18.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1272-1278, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32281336

RESUMO

Molecular biology is a new subject that clarifies the phenomena and nature of life at the molecular level. Its development provides new biotechnology and methods for the study of traditional pharmacognosy. The formation of molecular biology has brought the development of pharmacognosy into a new era of gene research. Lonicerae Japonicae Flos is a classical Chinese medicine. Many scholars of home and abroad have carried out relevant studies on its molecular biology on the basis of the in-depth study with traditional methods, and have achieved certain results. In order to provide references on the method, technical for promoting the modernization of Lonicerae Japonicae Flos, and the development, protection, and utilization of other traditional Chinese medicine resources. This article summarized the application status of molecular biology methods and techniques on the identification, biosynthesis of active constituents, and molecular mechanism of secondary metabolite under stress conditions of Lonicerae Japonicae Flos in recent years. In hybridization technology of tag(RFLP), molecular markers based on PCR(RAPD, AFLP, SSR and ISSR), based on DNA sequence analysis of SNP and DNA barcode for the variety identification, diagnosis, identification of Lonicerae Japonicae Flos, and so forth in detail. At the same time, it is proposed that multi-omics technology can be used to build systems biology technology and platforms, and establish related models of secondary metabolite biosynthesis, so as to deepen acknowledge the molecular mechanism of the active component biosynthesis of Lonicerae Japonicae Flos and the accumulation of metabolites, life activities of other medicinal plants under adverse environment, then to regulate them.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Lonicera/química , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Cromatografia Líquida de Alta Pressão , Código de Barras de DNA Taxonômico , Medicina Tradicional Chinesa , Repetições de Microssatélites , Plantas Medicinais/química , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Técnica de Amplificação ao Acaso de DNA Polimórfico , Metabolismo Secundário
19.
Fitoterapia ; 143: 104546, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32173423

RESUMO

Eight new compounds (Entanutilins O-V; 1-8), including four limonoids, two steroids, one triterpenoid and one lignan were isolated from the stem barks of Entandrophragma utile. Their structures were determined by detailed spectroscopic analyses (HRESIMS and 1D/2D-NMR). Bioactivity screening indicated that compounds 1, 6 and 7 exhibited effective in reversing resistance in MCF-7/DOX cells at a nontoxic concentration of 30 µM with 18.18-, 7.43- and 7.94-fold enhancing effect, respectively, meanwhile, compounds 5 and 6 showed moderate NO inhibitory activities in LPS-activated RAW 264.7 macrophages.


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Lignanas/farmacologia , Meliaceae/química , Esteroides/farmacologia , Triterpenos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Gana , Humanos , Lignanas/isolamento & purificação , Células MCF-7 , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Casca de Planta/química , Células RAW 264.7 , Esteroides/isolamento & purificação , Triterpenos/isolamento & purificação
20.
Br J Haematol ; 190(2): 274-283, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32103499

RESUMO

About 25% of patients with newly diagnosed acute myeloid leukaemia (AML) have normal cytogenetics and no nucleophosmin 1 (NPM1) mutation or Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD). The prognosis and best therapy for these patients is controversial. We evaluated 158 newly diagnosed adults with this genotype who achieved histological complete remission within two cycles of induction therapy and were assigned to two post-remission strategies with and without an allotransplant. Targeted regional sequencing at diagnosis was performed and data were used to estimate their prognosis, including relapse and survival. In multivariable analyses, having wild-type or mono-allelic mutated CCAAT/enhancer-binding protein alpha (CEBPA) [hazard ratio (HR) 2·39, 95% confidence interval (CI) 1·08-5·30; P = 0·032), mutated NRAS (HR 2·67, 95% CI 1·36-5·25; P = 0·004), mutated colony-stimulating factor 3 receptor (CSF3R) (HR 2·85, 95% CI 1·12-7·27; P = 0·028) and a positive measurable residual disease (MRD)-test after the second consolidation cycle (HR 2·88, 95% CI 1·32-6·30; P = 0·008) were independently correlated with higher cumulative incidence of relapse (CIR). These variables were also significantly associated with worse survival (HR 3·02, 95% CI 1·17-7·78, P = 0·022; HR 3·62, 95% CI 1·51-8·68, P = 0·004; HR 3·14, 95% CI 1·06-9·31, P = 0·039; HR 4·03, 95% CI 1·64-9·89, P = 0·002; respectively). Patients with ≥1 of these adverse-risk variables benefitted from a transplant, whereas the others did not. In conclusion, we identified variables associated with CIR and survival in patients with AML and normal cytogenetics without a NPM1 mutation or FLT3-ITD.


Assuntos
Análise Citogenética/métodos , Leucemia Mieloide Aguda/genética , Adolescente , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Sequências de Repetição em Tandem , Adulto Jovem
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