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1.
Acta Pharmacol Sin ; 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34934196

RESUMO

Cardiac hypertrophy, as one of the major predisposing factors for chronic heart failure, lacks effective interventions. Exploring the pathogenesis of cardiac hypertrophy will reveal potential therapeutic targets. S-nitrosylation is a kind of posttranslational modification that occurs at active cysteines of proteins to mediate various cellular processes. We here identified heat shock protein 90 (Hsp90) as a highly S-nitrosylated target in the hearts of rodents with hypertrophy, and the role of Hsp90 in cardiac hypertrophy remains undefined. The S-nitrosylation of Hsp90 (SNO-Hsp90) levels were elevated in angiotensin II (Ang II)- or phenylephrine (PE)-treated neonatal rat cardiomyocytes (NRCMs) in vitro as well as in cardiomyocytes isolated from mice subjected to transverse aortic constriction (TAC) in vivo. We demonstrated that the elevated SNO-Hsp90 levels were mediated by decreased S-nitrosoglutathione reductase (GSNOR) expression during cardiac hypertrophy, and delivery of GSNOR adeno-associated virus expression vectors (AAV9-GSNOR) decreased the SNO-Hsp90 levels to attenuate cardiac hypertrophy. Mass spectrometry analysis revealed that cysteine 589 (Cys589) might be the S-nitrosylation site of Hsp90. Delivery of the mutated AAV9-Hsp90-C589A inhibited SNO-Hsp90 levels and attenuated cardiac hypertrophy. We further revealed that SNO-Hsp90 led to increased interaction of glycogen synthase kinase 3ß (GSK3ß) and Hsp90, leading to elevated GSK3ß phosphorylation and decreased eIF2Bε phosphorylation, thereby aggravating cardiac hypertrophy. Application of GSK3ß inhibitor TWS119 abolished the protective effect of Hsp90-C589A mutation in Ang II-treated NRCMs. In conclusion, this study demonstrates a critical role of SNO-Hsp90 in cardiac hypertrophy, which may be of a therapeutic target for cardiac hypertrophy treatment.

2.
Angew Chem Int Ed Engl ; : e202115263, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34913233

RESUMO

Endohedral nitrogen fullerenes have been proposed as building blocks for quantum information processing due to their long spin coherence time. However, addressability of the individual electron spin levels in such a multiplet system of 4 S3/2 has never been achieved because of the molecular isotropy and transition degeneracy among the Zeeman levels. Herein, by molecular engineering, we lifted the degeneracy by zero-field splitting effects and made the multiple transitions addressable by a liquid-crystal-assisted method. The endohedral nitrogen fullerene derivatives with rigid addends of spiro structure and large aspect ratios of regioselective bis-addition improve the ordering of the spin ensemble. These samples empower endohedral-fullerene-based qudits, in which the transitions between the 4 electron spin levels were respectively addressed and coherently manipulated. The quantum geometric phase manipulation, which has long been proposed for the advantages in error tolerance and gating speed, was implemented in a pure electron spin system using molecules for the first time.

3.
Huan Jing Ke Xue ; 42(9): 4452-4461, 2021 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-34414745

RESUMO

A field experiment was conducted in moderately and severely Cd contaminated paddy fields in Beishan Town, Changsha City, Hunan Province. This study examined the effects of LS amendment (limestone+sepiolite), in combination with soil application and foliar spraying of Zn fertilizer, on Cd uptake in early and late rice plants. The results showed that: ① the application of LS (2250 kg·hm-2 and 4500 kg·hm-2) significantly increased pH and CEC values in paddy soil during the early and late rice seasons, but the addition of Zn fertilizer (90 kg/hm2) to soil and through foliar spraying (0.2 g·L-1 and 0.4 g·L-1) had no significant effects on the pH or CEC of the soil. ② LS application decreased concentrations of TCLP-Cd and CaCl2-Cd in the soils, by 11.5%-38.8% and 24.0%-81.0%, respectively, while neither of the treatments involving the addition of Zn fertilizer to soil or through foliar spraying had any significant effects on the concentrations of TCLP-Cd and CaCl2-Cd. ③Single treatments involving only LS amendment, Zn fertilizer in soil, or foliar spraying of Zn fertilizer also reduced Cd concentrations in brown rice, but to a lesser degree than the combined treatments. The combined treatments (L1Z1F1, L1Z1F2, L2Z1F1, and L2Z1F2) reduced Cd concentrations in brown rice by 64.9%-67.5% and 56.1%-80.6%, for early and late rice, respectively, while L2Z1F1 (4500 kg·hm-2 LS+90 kg·hm-2 Zn fertilizer+foliar spraying 0.2 g·L-1 Zn fertilizer) resulted in the largest reduction in Cd concentration in brown rice. ④ The Cd/Zn ratio in brown rice was significantly positively correlated with Cd concentrations, indicating that increased Zn concentration in different rice tissues was one of the key reasons for decreased Cd concentration in brown rice. Clearly, as a remediation technology, combining LS amendments with zinc fertilizer is an effective method for achieving the safe utilization of moderately and severely Cd contaminated paddy fields, by effectively inhibiting the uptake, accumulation, and transportation of Cd in rice plants and decreasing Cd concentrations in brown rice.


Assuntos
Oryza , Poluentes do Solo , Cádmio/análise , Fertilizantes , Solo , Poluentes do Solo/análise , Zinco/análise
4.
J Asian Nat Prod Res ; : 1-10, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34042537

RESUMO

In our previous studies, a kind of novel benzenesulfonamides was found to be a candidate insecticidal compounds. It was shown that propargyloxy and sulfonamide groups are pharmacodynamic groups. One hundred and twenty-six (126) naphthalenesulfonamides derivatives with propargyloxy functionality were designed and synthesized, and their insecticidal activities were determined. Some of them showed outstanding activity, with LC50 values as low as 0.202 mg ml-1, much lower than that of the positive control celangulin V (23.9 mg ml-1). In addition, the structure-activity relationships were discussed, and molecular docking was used to verify the binding mode of the compound and the target receptor.

5.
Oral Dis ; 27(6): 1366-1375, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32492239

RESUMO

OBJECTIVE: To explore the correlations between the habit of betel quid and areca nut (BQ-AN) chewing and the prognosis of oral cancer (OC). METHODS: We performed a systematic review and meta-analysis to clarify this issue. Data searches were performed using PubMed, Web of Science, Epistemonikos, and Embase databases through November 2019. The primary outcome was the difference in the prognosis of OC between BQ-AN chewers and non-chewers, measured in terms of 5-year overall survival (OS) and 5-year disease-specific survival (DSS) log (HR) reported in articles. The pooled HR with 95% CI of 5-year OS and 5-year DSS was calculated using a fixed-effects model. RESULTS: Ten articles with eleven OS or DSS survival studies (one of the articles contained two studies), which were published between 2003 and 2017, were eligible for inclusion in the present study. All the 11 studies were observational studies, among which 10 were retrospective and 1 was prospective. One study measured both OS and DSS. Eight studies, with a total of 2,761 patients, used 5-year OS as the primary endpoint and four studies, with a total of 2,551 patients, used 5-year DSS. Overall, the pooled HR evaluating BQ-AN chewers was 1.26 (95% CI: 1.09-1.46) for 5-year OS and 1.40 (95% CI: 1.15-1.70) for 5-year DSS, compared with non-chewers. There was a significant association between BQ-AN chewing and OC survival. CONCLUSIONS: Betel quid and areca nut chewing is significantly associated with poor prognosis in patients with OC.


Assuntos
Areca , Neoplasias Bucais , Areca/efeitos adversos , Humanos , Mastigação , Neoplasias Bucais/etiologia , Nozes , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos
6.
Nutr Neurosci ; : 1-10, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33078688

RESUMO

OBJECTIVE: To investigate the effect of maternal zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns. METHODS: Pregnant rats were divided into zinc adequate (ZA), zinc deficient (ZD), and paired fed (PF) groups. Serum zinc contents and AKP activity in mother rats and offspring at P21 (end of lactation) and P60 (weaned, adult) were detected. Cognitive ability of offspring at P21 and P60 were determined by Morris water maze. The expression of proteins including DNMT3a, DNMT1, GADD45ß, MeCP2 and BDNF in the offspring hippocampus were detected by Western-blot. The methylation status of BDNF promoter region in hippocampus of offspring rats was detected by MS-qPCR. RESULTS: Compared with the ZA and PF groups, pups in the ZD group had lower zinc levels and AKP activity in the serum, spent more time finding the platform and spent less time going through the platform area. Protein expression of DNMT1 and GADD45b were downregulated in the ZD group during P0 and P21 but not P60 compared with the ZA and PF group, these results were consistent with a reduction in BDNF protein at P0 (neonate), P21. However, when pups of rats in the ZD group were supplemented with zinc ion from P21 to P60, MeCP2 and GADD45b expression were significantly downregulated compared with the ZA and PF group. CONCLUSION: Post-weaning zinc supplementation may improve cognitive impairment induced by early life zinc deficiency, whereas it may not completely reverse the abnormal expression of particular genes that are involved in DNA methylation, binding to methylated DNA and neurogenesis.

7.
Acta Pharmacol Sin ; 41(2): 278-285, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31554961

RESUMO

Epigallocatechin gallate (EGCG), a major polyphenol in green tea, exhibits diverse biological activities. Previous studies show that EGCG could effectively suppress HBV gene expression and replication, but the role of EGCG in HBV replication and its underlying mechanisms, especially the signaling pathways involved, remain unclear. In this study we investigated the mechanisms underlying EGCG inhibition on HBV replication with a focus on the signaling pathways. We showed that EGCG (12.5-50 µM) dose-dependently inhibited HBV gene expression and replication in HepG2.2.15 cells. Similar results were observed in HBV mice receiving EGCG (25 mg· kg-1· d-1, ip) for 5 days. In HepG2.2.15 cells, we showed that EGCG (12.5-50 µM) significantly activate ERK1/2 MAPK signaling, slightly activate p38 MAPK and JAK2/STAT3 signaling, while had no significant effect on the activation of JNK MAPK, PI3K/AKT/mTOR and NF-κB signaling. By using specific inhibitors of these signaling pathways, we demonstrated that ERK1/2 signaling pathway, but not other signaling pathways, was involved in EGCG-mediated inhibition of HBV transcription and replication. Furthermore, we showed that EGCG treatment dose-dependently decreased the expression of hepatocyte nuclear factor 4α (HNF4α) both at the mRNA and protein levels, which could be reversed by pretreatment with the ERK1/2 inhibitor PD98059 (20 µM). Moreover, we revealed that EGCG treatment dose-dependently inhibited the activity of HBV core promoter and the following HBV replication. In summary, our results demonstrate that EGCG inhibits HBV gene expression and replication, which involves ERK1/2-mediated downregulation of HNF4α.These data reveal a novel mechanism for EGCG to inhibit HBV gene expression and replication.


Assuntos
Catequina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/administração & dosagem , Antivirais/farmacologia , Catequina/administração & dosagem , Catequina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Hepatite B/genética , Hepatite B/virologia , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo
8.
BMC Cancer ; 19(1): 1047, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694596

RESUMO

BACKGROUND: The application of laparoscopic liver resection (LLR) has expanded rapidly in recent decades. Although multiple authors have reported LLR shows improved safety and efficacy in treating hepatocellular carcinoma (HCC) compared with open liver resection (OLR), laparoscopic (LMLR) and open (OMLR) major liver resections for HCC treatment remain inadequately evaluated. This work aimed to test the hypothesis that LMLR is safer and more effective than OMLR for HCC. METHODS: Comparative cohort and registry studies on LMLR and OMLR, searched in PubMed, the Science Citation Index, EMBASE, and the Cochrane Library, and published before March 31, 2018, were collected systematically and meta-analyzed. Fixed- and random-effects models were employed for generating pooled estimates. Heterogeneity was assessed by the Q-statistic. RESULTS: Nine studies (1173 patients) were included. Although the pooled data showed operation time was markedly increased for LMLR in comparison with OMLR (weighted mean difference [WMD] 74.1, 95% CI 35.1 to 113.1, P = 0.0002), blood loss was reduced (WMD = - 107.4, 95% CI - 179.0 to - 35.7, P = 0.003), postoperative morbidity was lower (odds ratio [OR] 0.47, 95% CI 0.35 to 0.63, P <  0.0001), and hospital stay was shorter (WMD = - 3.27, 95% CI - 4.72 to - 1.81, P <  0.0001) in the LMLR group. Although 1-year disease-free survival (DFS) was increased in patients administered LMLR (OR = 1.55, 95% CI 1.04 to 2.31, P = 0.03), other 1-, 3-, and 5-year survival outcomes (overall survival [OS] and/or DFS) were comparable in both groups. CONCLUSIONS: Compared with OMLR, LMLR has short-term clinical advantages, including reduced blood loss, lower postsurgical morbidity, and shorter hospital stay in HCC, despite its longer operative time. Long-term oncological outcomes were comparable in both groups.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Fígado/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Humanos , Tempo de Internação/estatística & dados numéricos , Fígado/patologia , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos
9.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3637-3644, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602935

RESUMO

The biopharmaceutics classification system( BCS) is a scientific framework or method for classifying drugs based on drug solubility and permeability,which can be used to provide drug bioavailability-absorption correlation analysis. Based on the characteristics of multi-component and multi-target of traditional Chinese medicine( TCM) as well as the concept,method and technology of BCS,the research group proposed biopharmaceutics classification system of Chinese materia medica( CMMBCS) and carried out research and data accumulation of classical prescriptions. Based on the previous research results,further development ideas under the CMMBCS concept and framework were further proposed in this study. In the course of research,the influence of the intermediate links of the complex interactions of the multi-component environment was omitted,and the component absorption studies on the main clinical effects of prescription ingredients were directly concerned,or the components and data were reversely extracted from the aspects of metabolism,pharmacodynamic pathways and absorption principles. Studies were conducted from two aspects( single component and compound prescription) to comprehensively evaluate the absorption properties of TCM compound. In the research path,the different ways in which Chinese medicine could exert its efficacy were fully considered,and CMMBCS classification and establishment rules were clarified mainly by focusing on the absorption pathway into the blood. Specifically,the network pharmacology and molecular docking technology were used to screen the compound index components of TCM; the absorption rules were studied by the physiologically based pharmacokinetic models and the absorption parameters of CMMBCS were calculated by reverse reasoning. Then the CMMBCS classification of TCM prescription was corrected by studying the efficacy or absorption pathway. In this paper,the theoretical framework and research methodology of CMMBCS were systematically improved based on the establishment of CMMBCS basic theory,the supplementary of drug-oriented research ideas and the application of modern mature Chinese medicine methodology.


Assuntos
Biofarmácia/classificação , Medicamentos de Ervas Chinesas/classificação , Materia Medica/classificação , Simulação de Acoplamento Molecular
10.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3662-3671, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602938

RESUMO

The research on biopharmaceutics classification system of Chinese materia medica( CMMBCS) should be finally implemented to the holistic research level of traditional Chinese medicine compounds,while the overall biopharmaceutical properties of traditional Chinese medicine compounds are not only the sum of solubility and permeability of each component. In this study,Gegen Qinlian Tablets was used as the research object,and the contents of 12 representative components,i.e. puerarin,daidzin,baicalin,daidzein,wogonoside,baicalein,wogonin,glycyrrhizic acid,coptisine hydrochloride,epiberberine,berberine hydrochloride and palmatine hydrochloride,were simultaneously determined by HPLC to obtain the mass weight of each component. The in vitro lipopolysaccharide( LPS)-induced RAW264. 7 cells inflammation model was established to investigate the anti-inflammatory effects of 12 representative components and obtain the efficacy weight of each component. In order to obtain the number of doses and effective permeability coefficient which can represent the overall biopharmaceutical properties of Gegen Qinlian Tablets,mass weight was combined with efficacy weight to integrate the solubility and permeability data of each component determined by typical shake flask method and in situ single pass intestinal perfusion model respectively. The results indicated that Gegen Qinlian Tablets should be categorized Ⅳ drug of the CMMBCS with low solubility and low permeability.


Assuntos
Anti-Inflamatórios/farmacologia , Biofarmácia/classificação , Medicamentos de Ervas Chinesas/classificação , Materia Medica/classificação , Medicamentos de Ervas Chinesas/farmacologia , Comprimidos
11.
Artigo em Inglês | MEDLINE | ID: mdl-31569567

RESUMO

Childhood maltreatment is associated with risky sexual behaviors (RSBs). Previous systematic reviews and meta-analysis focused only on the relationship between childhood sexual abuse and RSBs, thus the association between childhood maltreatment and RSBs has yet to be systematically and quantitatively reviewed. We aimed to provide a systematic meta-analysis exploring the effect of childhood maltreatment and its subtypes on subsequent RSBs in adolescence and adulthood. PubMed, Google Scholar, EMBASE, Medline were searched for qualified articles up to April 2019. We calculated the pooled risk estimates using either the random-effect model or fixed-effect model. The potential heterogeneity moderators were identified by subgroup and sensitivity analysis. Overall, childhood maltreatment was significantly associated with an early sexual debut (odds ratio (OR) = 2.22; 95% confidence interval (CI): 1.64-3.00), multiple sexual partners (OR = 2.22; 95% CI: 1.78-2.76), transactional sex (OR = 3.05; 95% CI: 1.92-4.86) and unprotected sex (OR = 1.59; 95% CI: 1.22-2.09). Additionally, different types of childhood maltreatment were also significantly associated with higher risk of RSBs. Relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded consistent results. Childhood maltreatment is significantly associated with risky sexual behaviors. The current meta-analysis indicates it is vital to protect children from any types of maltreatment and provide health education and support for maltreated individuals.


Assuntos
Maus-Tratos Infantis/estatística & dados numéricos , Assunção de Riscos , Sexo sem Proteção/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Comportamento Sexual/estatística & dados numéricos , Adulto Jovem
12.
Theriogenology ; 132: 72-82, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31003067

RESUMO

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A) acts as a powerful coactivator of many transcriptional factors that relate to granulosa cell (GC) apoptosis. In this study, the miRNAs mediating goat follicular atresia and luteinized granulosa cell (LGC) apoptosis induced by hydrogen peroxide (H2O2) via PPARGC1A were investigated. Our results showed that miR-1197-3p targeted PPARGC1A was predicted by bioinformatics algorithm and verified by luciferase reporter assay. In addition, miR-1197-3p promoted goat LGC apoptosis via PPARGC1A through mitochondrial-dependent apoptosis pathway, and these effects could be restored by PPARGC1A overexpression. Moreover, H2O2-induced LGC apoptosis significantly upregulated miR-1197-3p expression and downregulated PPARGC1A level. Pretreatment of miR-1197-3p inhibitor alleviated LGC apoptosis induced by 400 µM H2O2 for 12 h, and preserved the mitochondrial membrane potential by increasing PPARGC1A expression. In conclusion, miR-1197-3p might act as an essential regulator of goat LGC apoptosis potentially via the mitochondrial-dependent apoptosis pathway by targeting PPARGC1A.


Assuntos
Apoptose/efeitos dos fármacos , Cabras , Células da Granulosa/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , MicroRNAs/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Animais , Sobrevivência Celular , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células da Granulosa/fisiologia , MicroRNAs/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética
13.
Cytotechnology ; 71(2): 563-572, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30767091

RESUMO

Bone mesenchymal stem cells (BMSCs) have the capacity to differentiate into germ cells (GCs). This study was conducted to develop a non-integrated method of using RNA transfection to derive putative male GCs from goat BMSCs (gBMSCs) in vitro by overexpressing STRA8, BOULE and DAZL. The gBMSCs were induced by co-transfection these three mRNAs together (mi-SBD group) or sequential transfection according to their expression time order in vivo (mi-S + BD group). After transfection, a small population of gBMSCs transdifferentiated into early germ cell-like cells and had the potential to enter meiosis. These cells expressed primordial germ cell specific genes STELLA, C-KIT and MVH, as well as premeiotic genes DAZL, BOULE, STRA8, PIWIL2 and RNF17. Importantly, the expression level of meiotic marker synaptonemal complex protein 3 significantly increased in these transfected two groups compared with control cells by qRT-PCR, immunofluorescence and western blot analysis (P < 0.05). Moreover, the protein expression of MVH was significantly higher in mi-S + BD group than that in mi-SBD group (P < 0.05). In addition, compared with control group, the methylation rate of imprinted gene H19 decreased in these two transfected group (P < 0.05), and the rate was significantly lower in mi-S + BD group compared with mi-SBD group (P < 0.05). This study helps to understand the mechanisms of action of key genes in GCs differentiation and also provides a novel system for in vitro induction of male GCs from stem cells.

14.
Reprod Domest Anim ; 54(1): 72-82, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30180283

RESUMO

The nutritional alteration of amino acids (AAs) profile in physiological fluid was poorly characterized in livestock. After oestrus synchronization, 24 ewes were randomly assigned to two groups based on the nutrient requirement recommended for maintenance (M): the feed-supplemented group (S, 1.5 × M, N = 12) and feed-restricted group (R, 0.5 × M, N = 12) on days 6-12 of their oestrous cycle, which occurred shortly before ovulation. The concentration of 30 AAs in peripheral blood (PB) and follicular fluid (FF) was quantified to calculate the PB-to-FF concentration gap for each AA and determine its correlation with metabolites and hormones in PB and FF. Results showed that the feed restriction enlarged the oestrous cycle length, decreased the number of follicles 2.5-3.5 mm, increased the number of follicles >3.5 mm and augmented the volume of follicles >2.5 mm. Nineteen AAs from PB were significantly different between the groups. The phosphoethanolamine (PEtN) and ration of essential AAs to nonessential AAs (EAA/NEAA) in FF significantly (p < 0.05) increased and decreased in the R group, respectively. Most AAs, except aspartate (Asp) and carnosine (Car) in the R group and alanine (aAla) in both groups, were significantly lower within FF than those within PB. The correlation of AAs with FSH and progesterone (P4 ) was more significant than that of AAs with other endocrine milieu characteristics. In conclusion, our results revealed that the influence of short-term nutritional manipulation during luteal phase on folliculogenesis might not be due to the variation of intrafollicular AAs profile but rather attribute to the peripheral blood AAs profile alteration.


Assuntos
Aminoácidos/sangue , Cromatografia Líquida de Alta Pressão/veterinária , Dieta/veterinária , Líquido Folicular/química , Animais , Cromatografia Líquida de Alta Pressão/métodos , Etanolaminas/análise , Feminino , Hormônio Foliculoestimulante/sangue , Líquido Folicular/metabolismo , Fase Luteal/sangue , Fase Luteal/metabolismo , Folículo Ovariano/fisiologia , Progesterona/sangue , Carneiro Doméstico/sangue , Carneiro Doméstico/metabolismo
15.
BMC Cancer ; 18(1): 643, 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29879928

RESUMO

BACKGROUND: The optimal therapeutic strategy in UICC stage T3 hepatocellular carcinoma (HCC) patients that maximizes both safety and long-term outcome has not yet been determined. Our aim was to compare clinical outcomes following hepatic resection (HR) versus transarterial chemoembolization (TACE) for stage T3 HCC. METHODS: From 2005 to 2013, 1179 patients with T3 HCC who underwent HR or TACE were divided into two groups, HR group (n = 280) or TACE group (n = 899). The clinical outcomes were compared before and after propensity score matching. RESULTS: The propensity model matched 244 patients in each group for further analyses. After matching, medium overall survival (OS), 1, 3, and 5-year OS rates in TACE group were 11.8 (95%CI, 9.9-13.7) months, 49.6, 16.5, and 8.4%, respectively; which in HR group were 17.8 (95% CI, 14.8-20.8) months, 63.1, 33.3, and 26.4%, respectively; (log rank = 19.908, P < 0.01). Patients in HR group were more likely to develop pleural effusion, compared with those in TACE group (0.4% vs. 5.3%, P = 0.01). However, no significant differences in other adverse events (AEs) were found between two groups. Similar results were also demonstrated prior to the matched analysis. Multivariate analysis indicated that prothrombin time (PT), tumor size, tumor numbers, UICC staging status, and initial treatment were independent prognostic factors. CONCLUSIONS: Our study revealed that TACE was an option for UICC T3 HCC patients. However, HR seemed to be safe and yield a survival benefit compared with TACE, especially for patients with a good underlying liver function.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Hepatectomia/métodos , Neoplasias Hepáticas/terapia , Adulto , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Feminino , Hepatectomia/efeitos adversos , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Análise de Sobrevida , Resultado do Tratamento
16.
Zhongguo Zhong Yao Za Zhi ; 43(11): 2269-2273, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29945378

RESUMO

To illustrate the intrinsic dissolution rate(IDR) involved in biopharmaceutics classification system of Chinese materia medica(CMMBCS), investigate the effect of artificial multicomponent environment on IDR of berberine, by using a non-disintegrating disk, and summarize related rules by using the obtained data. Progressive levels design was used to investigate the effects of single component environment (puerarin, baicalin, and glycyrrhizic acid); double-component environment(puerarin+baicalin, puerarin+ glycyrrhizic acid, baicalin+glycyrrhizic acid); and triple-component environment(puerarin+baicalin+glycyrrhizic acid) on IDR of berberine, laying a foundation for further researches on the absorption mechanism of multiple components.


Assuntos
Berberina/química , Medicamentos de Ervas Chinesas/química , Materia Medica , Biofarmácia , Solubilidade
17.
Environ Sci Pollut Res Int ; 25(15): 15006-15018, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29552716

RESUMO

A growing body of evidence has shown bisphenol A (BPA), an estrogen-like industrial chemical, has adverse effects on the nervous system. In this study, we investigated the transcriptional behavior of long non-coding RNAs (lncRNAs) and mRNAs to provide the information to explore neurotoxic effects induced by BPA. By microarray expression profiling, we discovered 151 differentially expressed lncRNAs and 794 differentially expressed mRNAs in the BPA intervention group compared with the control group. Gene ontology analysis indicated the differentially expressed mRNAs were mainly involved in fundamental metabolic processes and physiological and pathological conditions, such as development, synaptic transmission, homeostasis, injury, and neuroinflammation responses. In the expression network of the BPA-induced group, a great number of nodes and connections were found in comparison to the control-derived network. We identified lncRNAs that were aberrantly expressed in the BPA group, among which, growth arrest specific 5 (GAS5) might participate in the BPA-induced neurotoxicity by regulating Jun, RAS, and other pathways indirectly through these differentially expressed genes. This study provides the first investigation of genome-wide lncRNA expression and correlation between lncRNA and mRNA expression in the BPA-induced neurotoxicity. Our results suggest that the elevated expression of lncRNAs is a major biomarker in the neurotoxicity induced by BPA.


Assuntos
Compostos Benzidrílicos/toxicidade , Neurotoxinas/toxicidade , Fenóis/toxicidade , RNA Longo não Codificante/metabolismo , Animais , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Análise de Sequência com Séries de Oligonucleotídeos , Células PC12 , RNA Mensageiro/metabolismo , Ratos , Análise Serial de Tecidos
18.
Nutr Neurosci ; 21(7): 478-486, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28421879

RESUMO

OBJECTIVE: To explore Zn2+ deficiency-induced neuronal injury in relation to DNA methylation, providing valuable data and basic information for clarifying the mechanism of Zn2+ deficiency-induced neuronal injury. METHODS: Cultured hippocampal neurons were exposed to the cell membrane-permeant Zn2+ chelator N,N,N',N'-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) (2 µM), and to TPEN (2 µM) plus ZnSO4 (5 µM) for 24 hours. We analyzed intracellular Zn2+ levels, neuronal viability, and protein/mRNA levels for DNA (cytosine-5) methyltransferase 1 (DNMT1), DNA (cytosine-5-) methyltransferase 3 alpha (DNMT3a), methyl CpG binding protein 2 (MeCP2), Brain-derived neurotrophic factor (BDNF), and growth arrest and DNA-damage-inducible, beta (GADD45b) in the treated neurons. RESULTS: We found that exposure of hippocampal neurons to TPEN (2 µM) for 24 hours significantly reduced intracellular Zn2+ concentration and neuronal viability. Furthermore, DNMT3a, DNMT1, BDNF, and GADD45b protein levels in TPEN-treated neurons were significantly downregulated, whereas MeCP2 levels were, as expected, upregulated. In addition, DNMT3a and DNMT1 mRNA levels in TPEN-treated neurons were downregulated, while MeCP2, GADD45b, and BDNF mRNA were largely upregulated. Addition of ZnSO4 (5 µM) almost completely reversed the TPEN-induced alterations. CONCLUSION: Our data suggest that free Zn2+ deficiency-induced hippocampal neuronal injury correlates with free Zn2+ deficiency-induced changes in methylation-related protein gene expression including DNMT3a/DNMT1/MeCP2 and GADD45b, as well as BDNF gene expression.


Assuntos
Metilação de DNA , Hipocampo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Zinco/deficiência , Animais , Antígenos de Diferenciação/genética , Antígenos de Diferenciação/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , DNA (Citosina-5-)-Metiltransferase 1/genética , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Etilenodiaminas/toxicidade , Regulação da Expressão Gênica , Hipocampo/citologia , Proteína 2 de Ligação a Metil-CpG/genética , Proteína 2 de Ligação a Metil-CpG/metabolismo , Neurônios/patologia , Ratos , Ratos Wistar
19.
Zhongguo Zhong Yao Za Zhi ; 42(21): 4127-4134, 2017 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-29271150

RESUMO

One of the advantages of biopharmaceutics classification system of Chinese materia medica (CMMBCS) is expanding the classification research level from single ingredient to multi-components of Chinese herb, and from multi-components research to holistic research of the Chinese materia medica. In present paper, the alkaloids of extract of huanglian were chosen as the main research object to explore their change rules in solubility and intestinal permeability of single-component and multi-components, and to determine the biopharmaceutical classification of extract of Huanglian from holistic level. The typical shake-flask method and HPLC were used to detect the solubility of single ingredient of alkaloids from extract of huanglian. The quantitative research of alkaloids in intestinal absorption was measured in single-pass intestinal perfusion experiment while permeability coefficient of extract of huanglian was calculated by self-defined weight coefficient method.


Assuntos
Medicamentos de Ervas Chinesas/química , Materia Medica/classificação , Extratos Vegetais/química , Animais , Biofarmácia , Medicamentos de Ervas Chinesas/classificação , Absorção Intestinal , Extratos Vegetais/classificação
20.
Zhongguo Zhong Yao Za Zhi ; 42(8): 1525-1531, 2017 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29071857

RESUMO

To investigate the overall intestinal permeability of multiple components in lotus leaves and make clear the interaction in composition absorption process. Rat single-pass intestinal perfusion technique was used, and the results showed that the Peff values of nuciferine, demethylanuciferine, rutin, quercetin, kaempferol from lotus leaf were greater than 0.5×10⁻4 cm•s⁻¹. In the biopharmaceutics classification system (BCS) intestinal permeability property, these ingredients were high permeable components, while the hyperin was low permeable component. However, in the multi-component environment of the lotus leaf extract, component permeation was changed. Semi quantitative analysis of the unclear components showed that under the multi-component environment, four in seven components with relatively high contents had a Peff value less than 0.5×10⁻4 cm•s⁻¹, indicating these 4 components were of low permeability, while other 3 components were of high permeability. The results could be valuable to make clear the overall intestinal permeability of multiple components in lotus leaf, and lay a foundation for studying the mechanism of the lipid-lowering effect of lotus leaf.


Assuntos
Absorção Intestinal , Intestinos/efeitos dos fármacos , Nelumbo/química , Extratos Vegetais/farmacocinética , Animais , Biofarmácia , Perfusão , Permeabilidade , Folhas de Planta/química , Ratos
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