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1.
Phys Chem Chem Phys ; 25(13): 9685, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36919711

RESUMO

Correction for 'Noncovalent wedging effect catalyzed the cis to syn transformation of a surface-adsorbed polymer backbone toward an unusual thermodynamically stable supramolecular product' by Zhi-Xuan Liu et al., Phys. Chem. Chem. Phys., 2022, 24, 30010-30016, https://doi.org/10.1039/D2CP04184G.

2.
Phys Chem Chem Phys ; 24(48): 30010-30016, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36472299

RESUMO

The significant influence of noncovalent interactions on catalytic processes has been recently appreciated but is still in its infancy. In this report, it is found that wedging Me-PTCDI (small-molecule) between the alkyl chains of PffBT4T-2OD (polymer) and a graphite substrate can reduce the energy barrier of flipping over the surface-adsorbed alkylthiophene group from the cis to syn conformation, revealing the catalytic role of Me-PTCDI via a noncovalent wedging effect. The wedging of Me-PTCDI brings the interactions between the alkyl chains and substrate to a very weak level by lifting up the alkyl chains, which eliminates the major hindrance of the flipping process to one main factor: the torsion of the dihedral angles of the thiophene group. The Me-PTCDI/syn PffBT4T-2OD arrangement shows unusual stability compared to the cis one because the syn conformation allows the alkyl chains to construct dense lamella and facilitates interactions between Me-PTCDI and the syn PffBT4T-2OD backbones. The results are helpful for boosting the development of noncovalent catalysis and bottom-up fabrications toward devices functionalized at a molecular level.

3.
BMC Endocr Disord ; 20(1): 138, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894113

RESUMO

BACKGROUND: The specific underlying pathogenesis of prolactinoma has not been clarified yet, to the best of our knowledge. p38 mitogen-activated protein kinase (MAPK) signaling including p38α MAPK (MAPK14), p38ß (MAPK11), p38γ (MAPK12) and p38δ (MAPK13) is associated with the development and progression of several types of cancer. METHODS: Immunofluorescence analysis was performed on the prolactin (PRL) and MAPK14 expressions of pituitary gland in C57BL/6 mice and human prolactinoma specimen. In the present study, the role of MAPK14 in prolactinoma was determined using estradiol-induced mice and dopamine D2 receptor knockout (DRD2-/-) mice models in C57BL/6 wild-type (WT), MAPK14-/- and DRD2-/-MAPK14+/- mice. GH3 cells were transfected with different sets of MAPK14 small interfering RNA, which to study MAPK14 and PRL expression in GH3 cells. RESULTS: Immunofluorescence analysis showed that PRL and MAPK14 expression were colocalized and increased in the pituitary gland of mice and human prolactinoma specimen compared with the control specimen. It was shown that PRL and MAPK14 expression was colocalized and increased significantly in the pituitary gland of estradiol-injected prolactinoma mice compared with the control mice. Knockout of MAPK14 significantly inhibited tumor overgrowth, and PRL expression was decreased in estradiol-induced mice. Furthermore, MAPK14 knockout of DRD2-/-MAPK14+/- mice significantly reduced the overgrowth of pituitary gland and PRL production and secretion compared with DRD2-/- mice. MAPK14 knockout using siRNA inhibited PRL production in GH3 cells. CONCLUSION: These results suggest that MAPK14 serves a promoting role in the formation of prolactinoma, and highlights the potential of MAPK14 as a potential therapeutic target in the treatment of prolactinoma.


Assuntos
Proteína Quinase 14 Ativada por Mitógeno/antagonistas & inibidores , Neoplasias Hipofisárias/patologia , Prolactinoma/patologia , RNA Interferente Pequeno/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Células Cultivadas , Feminino , Deleção de Genes , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Quinase 14 Ativada por Mitógeno/genética , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo , Prolactina/genética , Prolactina/metabolismo , Prolactinoma/genética , Prolactinoma/metabolismo , Ratos , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Somatotrofos/metabolismo , Somatotrofos/patologia
4.
Environ Toxicol ; 35(11): 1234-1240, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32621571

RESUMO

As a natural compound, resveratrol (Res) is confirmed to be promising drug for the treatment of malignant tumors. Therefore, our study aimed to observe the impacts of Res on the proliferation and apoptosis of oral squamous cell carcinoma cells (HSC-3 cells) as well as the mechanism involving chromobox protein homolog 7 (CBX7) signal transduction. HSC-3 cells were treated with Res, Akt agonist (AL3818) and p16 inhibitor (SC79), and transfected with CBX7 mimics and inhibitor plasmids. The CCK-8 assay was used to detect cell proliferation, flow cytometry was performed to assess cell cycle and apoptosis, and cell colonies and histone DNA level were also measured. Western blot analysis was used to determine the expression levels of related proteins. HSC-3 cells showed decreased cell proliferation, colonies, BrdU-counled cells and increased apoptosis, histone DNA level, the activities of caspase-3 and caspase-9 when treated with Res. Western blot analysis revealed elevated Cle-PARP and Cle-caspase 3 expression and reduced t-PARP expression in HSC-3 cells treated with Res compared with control. AL3818 and SC79 could decrease the inhibitory effects of Res on the growth of HSC-3 cells. Furthermore, CBX7 overexpression could also partly reverse the roles of Res in the growth of HSC-3 cells, and Akt and p16 signal transduction. Our results demonstrate that Res suppresses the proliferation, and induces the apoptosis of oral squamous cell carcinoma cells through the inhibition of CBX7/Akt and the activation of p16 cascades.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Resveratrol/uso terapêutico , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3 , Caspase 9 , Ciclo Celular , Linhagem Celular Tumoral , Humanos , Neoplasias Bucais , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Resveratrol/farmacologia , Transdução de Sinais
5.
Zhongguo Zhong Yao Za Zhi ; 45(10): 2232-2238, 2020 May.
Artigo em Zh | MEDLINE | ID: mdl-32495575

RESUMO

In this study, Donghua Hospital information management system and Meikang clinical pharmacy management system were used to collect medical records of all inpatients diagnosed as coronavirus disease 2019(COVID-19) in Wuhan Third Hospital. The statistics was based on the data of the cases treated with Ganlu Xiaodu Decoction, including demographic statistics, clinical cha-racteristics before medication, outcome of after medication and efficacy of drug combination. Excel 2003 and SPSS Clementine 12.0 software were used to conduct statistics on the included cases, and Apriori algorithm and association rules were used for the association analysis on drug combination. A total of 131 cases of COVID-19 were treated with Ganlu Xiaodu Decoction combined with Chinese and Western medicine. All of the patients were cured and discharged. The drug combination mainly included Ganlu Xiaodu Decoction, abidor, Lianhua Qingwen, moxifloxacin, Qiangli Pipa Lu, vitamin C, glycyrrhizinate diammonium, pantoprazole and Shufeng Jiedu. There is a certain regularity and effectiveness in the treatment of COVID-19 infection patients with the combination of Ganlu Xiaodu Decoction and other drugs, but the rationality and safety still need to be further verified.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Medicina Tradicional Chinesa , Pandemias , Pneumonia Viral , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Humanos , Pneumonia Viral/tratamento farmacológico , SARS-CoV-2 , Tratamento Farmacológico da COVID-19
6.
Zhonghua Nan Ke Xue ; 25(7): 586-589, 2019 Jul.
Artigo em Zh | MEDLINE | ID: mdl-32223097

RESUMO

OBJECTIVE: To study the effect of a new human sperm freezing method on the sperm recovery rate and search for an optimal method for cryopreservation of human epididymal sperm. METHODS: We collected semen samples from 76 men with obstructive azoospermia by percutaneous epididymal sperm aspiration and divided each sample into two parts to be cryopreserved with a self-made metal freezing plate (the experimental group) or by slow freezing (the control group), respectively. We measured the percentage of progressively motile sperm (PMS) with the computer-assisted semen analysis system and compared the membrane function, DNA fragmentation index (DFI), acrosin activity and morphological abnormality of the sperm between the two groups before and after cryopreservation. RESULTS: After thawing, both the percentages of PMS and hypotonically swollen sperm were significantly higher in the experimental than in the control group (ï¼»12.0 ± 7.5ï¼½% vs ï¼»8.0 ± 5.1ï¼½%, P < 0.05; ï¼»22.0 ± 17.5ï¼½% vs ï¼»18.0 ± 20.5ï¼½%, P < 0.05), though both decreased in comparison with the pre-freezing parameters (ï¼»20.7 ± 8.8ï¼½% and ï¼»30.0 ± 13.5ï¼½%) (P < 0.05). The sperm acrosin activity was remarkably higher in the experimental than in the control group after thawing (ï¼»75.2 ± 9.5ï¼½ vs ï¼»55.7 ± 8.3ï¼½ µIU/106sperm, P < 0.05), though decreased as compared with the baseline (ï¼»120.0 ± 10.5ï¼½ µIU/106 sperm, P < 0.05). No statistically significant differences were observed between the experimental and the control groups after thawing in the percentage of morphologically abnormal sperm (ï¼»98.7 ± 8.8ï¼½% vs ï¼»98.5±9.2ï¼½%, P > 0.05) or sperm DFI ï¼»38.2 ± 8.5ï¼½% vs ï¼»39.5 ± 10.2ï¼½%, P > 0.05), though both markedly elevated in comparison with the pre-freezing parameters (ï¼»97.2 ± 9.5ï¼½% and ï¼»30.8 ± 9.7ï¼½%) (P < 0.05). The post-thaw recovery rate of sperm was significantly higher in the experimental than in the control group (ï¼»65.2 ± 12.0ï¼½% vs ï¼»52.3 ± 18.0ï¼½%, P < 0.05). CONCLUSIONS: The self-made metal freezing plate, with its advantages of low cost, high efficiency, and easy operation, can be used as an effective method for cryopreservation of human sperm to achieve a high post-thaw sperm recovery rate, progressive sperm motility, and sperm acrosin activity.


Assuntos
Criopreservação/instrumentação , Preservação do Sêmen/instrumentação , Motilidade dos Espermatozoides , Congelamento , Humanos , Masculino , Metais , Espermatozoides
7.
Materials (Basel) ; 17(1)2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38203912

RESUMO

Polymeric dielectrics exhibit remarkable dielectric characteristics and wide applicability, rendering them extensively employed within the domain of electrical insulation. Nevertheless, the electrical strength has always been a bottleneck, preventing its further utilization. Nanocomposite materials can effectively improve insulation strength, but uniform doping of nanofillers in engineering applications is a challenge. Consequently, a nanocomposite interfacial coating was meticulously designed to interpose between the electrode and the polymer, which can significantly improve DC breakdown performance. Subsequently, the effects of filler concentration and coating duration on DC breakdown performance, high field conductivity, and trap distribution characteristics were analyzed. The results indicate that the composite coating introduces deep traps between the electrode-polymer interface, which enhances the carrier confinement, resulting in reduced conductivity and enhanced DC breakdown strength. The incorporation of a composite coating at the interface between the electrode and polymer presents novel avenues for enhancing the dielectric insulation of polymers.

8.
Hum Exp Toxicol ; 41: 9603271221080236, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35099304

RESUMO

OBJECTIVE: Cytochrome P450 3A5 (CYP3A5) is a highly polymorphic gene and the encoded protein variants differ in catalytic activity, leading to inter-individual variation in metabolic ability. The aim of the current study was to investigate the effects of seven allelic variants on the ability of CYP3A5 to metabolize sorafenib in vitro and further explore the impacts of CYP3A5 polymorphism on the proliferation and apoptosis of hepatocellular carcinoma cell line (HepG2) induced by sorafenib. METHODS: Wild-type and variant CYP3A5 enzymes were expressed in Spodoptera frugiperda insect cells using a baculovirus dual-expression system, and protein expression was checked by western blot. The enzymes were incubated with sorafenib at 37°C for 30 min, and formation of the major metabolite sorafenib N-oxide was assayed using ultra-performance liquid chromatography and tandem mass spectrometry. Intrinsic clearance values (Vmax/Km) were calculated for each enzyme. Additionally, recombinant HepG2 cells transfecting with CYP3A5 variants were used to investigate the effects of sorafenib on the proliferation of HepG2 cells. RESULTS: Intrinsic clearance of the six variants CYP3A5*2, CYP3A5*3A, CYP3A5*3C, CYP3A5*4, CYP3A5*5, and CYP3A5*7 was 26.41-71.04% of the wild-type (CYP3A5*1) value. In contrast, the clearance value of the variant CYP3A5*6 was significantly higher (174.74%). Additionally, the decreased ATP levels and cell viability and the increased cell apoptosis in HepG2 cells transfected with CYP3A5*2, CYP3A5*3A, CYP3A5*3C, CYP3A5*4, CYP3A5*5, and CYP3A5*7 were observed, whereas, the increased ATP levels and cell viability and the reduced cell apoptosis in HepG2 cells transfected with CYP3A5*6 were also investigated when compared to CYP3A5*1. CONCLUSION: Our results suggest that CYP3A5 polymorphism influences sorafenib metabolism and pharmacotherapeutic effect in hepatic carcinomas. These data may help explain differential response to drug therapy for hepatocellular carcinoma, and they support the need for individualized treatment.


Assuntos
Antineoplásicos/toxicidade , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Citocromo P-450 CYP3A/genética , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/toxicidade , Sorafenibe/uso terapêutico , Antineoplásicos/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Polimorfismo Genético , Sorafenibe/metabolismo , Células Tumorais Cultivadas
9.
J Mol Graph Model ; 115: 108214, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35598558

RESUMO

Recently low-energy-gap benzoindenothiophene (BIT)-based organic dyes have been experimentally sensitized to dye-sensitized solar cells (DSSCs) with impressive 10.9% power conversion efficiency. This paper presents a computational study of the modification of BIT-based dyes with fused thiophene moieties to build novel low band gap sensitizers. Density functional theory (DFT), tight-binding DFT, and time dependent DFT (TDDFT) approaches are used to demonstrate the electronic and optical properties of the BIT dyes and dye/(TiO2)46 complexes. Our calculations show that the structural modification by using fused thiophenes can effectively lower the band gap of the BIT dyes by 0.07-0.12 eV and affect the optical properties of BIT dyes. Enlarging the thiophene unit in BIT with thienothiophene and dithienothiophene improves the oscillator strength by 14%-25%, while the lowest-energy absorption peak basically remains at 559 nm. The incorporation of cyclopentadithiophene unit leads to a significant 47 nm red-shift of absorption peak and a 25% enhanced oscillator strength, compared to the original BIT dye. Those fused thiophenes modified BIT dyes also demonstrate ideal molecular orbital distribution patterns and ultra-fast injection time at the dye/(TiO2)46 interface. Our calculations provide useful guidance for the molecular design of novel naphthalene-based dyes for DSSC optimizations.

10.
Front Pharmacol ; 13: 888522, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35865960

RESUMO

Background: The dopamine D2 receptor (DRD2) plays an important role in the increased prolactin (PRL) levels associated with the pathogenesis of antipsychotic drugs (ADs). Elevated prolactin levels can affect people's quality of life. Maiya alkaloids has been used to treat diseases associated with high PRL levels. Maiya, is a processed product of the mature fruits of Hordeum vulgare L. (a gramineous plant) after sprouting and drying and also a common Chinese herbal drug used in the clinic, is traditionally used to treat abnormal lactation, and is currently used clinically for the treatment of abnormal PRL levels. Aims: Epigenetic mechanisms can be related to DRD2 expression. We investigated the role of DRD2 methylation in the induction of PRL expression by ADs and the mechanism underlying the effects of total barley maiya alkaloids (TBMA) on this induction. Methods: The methylation rate of DRD2 in 46 people with schizophrenia who took risperidone was detected by MassARRAY sequencing. Humans were long term users of Ris. Seventy Sprague Dawley female rats were divided into seven groups. A rat model of risperidone-induced PRL was established, and the potential protective effects of TBMA and its components [e.g., hordenine (Hor)] on these increased PRL levels were investigated. The PRL concentration was detected by Enzyme-linked immunosorbent assay. PRL, DRD2, and DNA methyltransferase (DNMT1, DNMT3α, and DNMT3ß) protein and mRNA expression were detected by western blotting and real-time polymerase chain reaction (RT-PCR), respectively. The positive rate of methylation in the DRD2 promoter region of rats was detected by MassARRAY sequencing. Results: Clinical studies showed that the positive rate of DRD2 methylation associated with increased PRL levels induced by ADs was significantly higher than in the normal prolactinemia (NPRL) group. In vivo and vitro, TBMA and Hor inhibited this induction of PRL expression and increased DRD2 expression by inhibiting the expression of the DNMTs. Conclusions: TBMA and hordenine increased DRD2 expression by inhibiting DNMT-dependent DRD2 methylation.

11.
Zhonghua Yi Xue Za Zhi ; 91(35): 2501-5, 2011 Sep 20.
Artigo em Zh | MEDLINE | ID: mdl-22321850

RESUMO

OBJECTIVE: To investigate the effects of Ginkgo biloba extract (GBE) on the expression of endothelial nitric oxide synthase (eNOS) and the release of nitric oxide (NO) in mesenteric arterioles of aging rats. METHODS: (1) Cytologic experiment:human umbilical vein endothelial cells (HUVEC) were randomly divided into 3 groups: control group, NG-nitro-L-arginine methyl ester (L-NAME) group and GBE group. L-NAME group: 100 µmol/L L-NAME was added into HUNEC for a 48-hour incubation. GBE group: After HUVEC was exposed to 100 µmol/L L-NAME for 24 hours, 20 g/L GBE was added for another 24-hour co-incubation. Then the expression of eNOS protein was observed in each group. (2) Animal experiment: Thirty-two 24-month-old male SD rats were randomly divided into normal control group (n = 8) and GBE group (n = 24). The GBE group was further divided into 3 groups receiving an orally dosed GBE for 3, 5, 7 days respectively. Afterward the diameter of first-order mesenteric arteriole was measured under the pressures of 20, 40, 60, 80, 100, 120, 140 mm Hg (1 mm Hg = 0.133 kPa) and the elasticity of blood vessels calculated. The release of NO, the expression of eNOS protein and its mRNA in mesenteric arterioles stimulated by the same shear stress (15 dyn/cm(2)) were evaluated respectively. RESULTS: (1) Cytological studies indicated that the expression of eNOS protein of the L-NAME group was significantly lower than those of the control and GBE groups (0.57 ± 0.06 vs 0.96 ± 0.05, 0.81 ± 0.09, both P < 0.01). (2) After the dosing of GBE for 3, 5, 7 days, the release of NO was significantly higher than that of the control group [(8.01 ± 0.24, 12.11 ± 0.78, 14.72 ± 0.70 vs 5.83 ± 0.75) pmol×mm(-2)×min(-1), all P < 0.05]; the expressions of eNOS protein were significantly higher than those of the control group (0.59 ± 0.20, 0.86 ± 0.02, 1.09 ± 0.13 vs 0.41 ± 0.16, all P < 0.05). And GBE was highest at Day 7; the expression levels of eNOS mRNA were significantly higher than those of the control group (0.79 ± 0.04, 0.85 ± 0.07, 0.99 ± 0.03 vs 0.58 ± 0.05, all P < 0.05). And GBE was also highest at Day 7. CONCLUSION: GBE can improve vascular flexibility through increasing the expression of eNOS and the release of NO, protecting the functions of blood vessels.


Assuntos
Arteríolas , Óxido Nítrico , Animais , Ginkgo biloba , Humanos , NG-Nitroarginina Metil Éster , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Sprague-Dawley
12.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(9): 2462-6, 2011 Sep.
Artigo em Zh | MEDLINE | ID: mdl-22097849

RESUMO

In the present study, based on the leaf-level hyperspectral data of BaiMu, LeiZhu and WuHuanZi, the authors come up with two solutions through the theory of statistics; the first one is that optimal discriminating band between tree species is extracted by mean interval confidence, the other one is that tree species is discriminated by the Manhattan distance and the Min Max interval similarity. The research results showed that (1) the optimal discriminating bands between BaiMu and LeiZhu are around 350-446, 497-527, 553-1 330, 1 355-2 400 and 2 436-2 500 nm; the optimal discriminating bands between BaiMu and WuHuanZi are around 434-555, 580-1 903, 1 914-2 089, 2 172-2 457 and 2 475-2 500 nm; the optimal discriminating bands between LeiZhu and WuHuanZi are around 434-555, 580-1 903, 1 914-2 089, 2 172-2 457 and 2 475-2 500 nm; and this result is helpful for us to find maximum difference to identifying tree species respectively. (2) In these optimal discriminating bands, we find that the Manhattan distance between the same species is far less than the different species; but the Min-Max interval similarity between the same species is far more than the different species, so this result could help us to discriminate and identify different types of tree species effectively.


Assuntos
Análise Espectral , Árvores/classificação , Intervalos de Confiança , Folhas de Planta
13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(11): 3010-3, 2011 Nov.
Artigo em Zh | MEDLINE | ID: mdl-22242506

RESUMO

In the present study, based on the leaf-level hyperspectral data of MaoZhu, LeiZhu and XiaoShunZhu, We come up with two solutions to discrimination through the theory of non-parametric test and pattern recognition; the first one is that optimal discriminating band between bambusoideae species is extracted by Mann-Whitney non-parametric test, the other is that bambusoideae species is discriminated by the support vector machine. The research results showed that (1) the optimal discriminating band between MaoZhu and LeiZhu is around 503-655, 689-732, 757-1 000, 1 038-1 084, 1 238-1 311, 1 404-1 591, 1682-1 800, 1 856-1 904, and 1 923-2 500 nm; the optimal discriminating band between MaoZhu and XiaoShunZhu is around 350-386, 731-1 430, 1 584-1 687, and 1 796-1 873 nm; the optimal discriminating band between LeiZhu and XiaoShunZhu is around 355-356, 498-662, 689-745, and 1 344-2 500 nm; and it can eliminate 30.0%, 57.7%, and 35.8% of the invalid distinction between bands by Mann-Whitney non-parametric test method. (2) In these optimal discriminating bands, we found that the accuracy of bambusoideae discrimination is 98.4%, 93.5%, and 95.1%, the generalization accuracy is 93.3%, 90.0%, and 86.7% by sequential minimal optimization algorithm. It indicates that this method is valid for selecting feature band and discriminating bambusoideae species.


Assuntos
Bambusa/classificação , Análise Espectral , Máquina de Vetores de Suporte , Algoritmos , Folhas de Planta , Estatísticas não Paramétricas
14.
Hum Exp Toxicol ; 40(12_suppl): S646-S653, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34784831

RESUMO

OBJECTIVE: Cytochrome P450 3A5 (CYP3A5) is a highly polymorphic gene and the encoded protein variants differ in catalytic activity, leading to inter-individual variation in metabolic ability. The aim of the current study was to investigate the effects of seven allelic variants on the ability of CYP3A5 to metabolize sorafenib in vitro and further explore the impacts of CYP3A5 polymorphism on the proliferation and apoptosis of hepatocellular carcinoma cell line (HepG2) induced by sorafenib. METHODS: Wild-type and variant CYP3A5 enzymes were expressed in Spodoptera frugiperda insect cells using a baculovirus dual-expression system, and protein expression was checked by western blot. The enzymes were incubated with sorafenib at 37°C for 30 min, and formation of the major metabolite sorafenib N-oxide was assayed using ultra-performance liquid chromatography and tandem mass spectrometry. Intrinsic clearance values (Vmax/Km) were calculated for each enzyme. Additionally, recombinant HepG2 cells transfecting with CYP3A5 variants were used to investigate the effects of sorafenib on the proliferation of HepG2 cells. RESULTS: Intrinsic clearance of the six variants CYP3A5*2, CYP3A5*3A, CYP3A5*3C, CYP3A5*4, CYP3A5*5, and CYP3A5*7 was 26.41-71.04% of the wild-type (CYP3A5*1) value. In contrast, the clearance value of the variant CYP3A5*6 was significantly higher (174.74%). Additionally, the decreased ATP levels and cell viability and the increased cell apoptosis in HepG2 cells transfected with CYP3A5*2, CYP3A5*3A, CYP3A5*3C, CYP3A5*4, CYP3A5*5, and CYP3A5*7 were observed, whereas, the increased ATP levels and cell viability and the reduced cell apoptosis in HepG2 cells transfected with CYP3A5*6 were also investigated when compared to CYP3A5*1. CONCLUSION: Our results suggest that CYP3A5 polymorphism influences sorafenib metabolism and pharmacotherapeutic effect in hepatic carcinomas. These data may help explain differential response to drug therapy for hepatocellular carcinoma, and they support the need for individualized treatment.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Citocromo P-450 CYP3A/genética , Neoplasias Hepáticas/tratamento farmacológico , Polimorfismo Genético , Sorafenibe/uso terapêutico , Antineoplásicos/farmacocinética , Humanos , Sorafenibe/farmacocinética
15.
Endocr Relat Cancer ; 28(7): 433-448, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-33974557

RESUMO

Prolactinomas have harmful effects on human health, and the pathogenesis is still unknown. Furthermore, 25% of prolactinoma patients do not respond to the therapy of dopamine receptor agonist in the clinic. Thus, it is important to reveal the pathogenesis and develop new therapeutic methods for prolactinomas. Herein, two animal models of prolactinomas, namely oestrogen-treated rats and transgenic D2 dopamine receptor-deficient mice, were used. PET/CT imaging detection showed that translocator protein-mediated microglia activation and inflammation significantly increased in the pituitary glands of prolactinomas rats. Messenger RNA microarrays were used to analyze and compare the differential gene and signal pathways of the pituitary glands between control and prolactinomas rats. Statistical results pertaining to gene enrichment showed that the innate immune response genes were upregulated in the pituitary glands of prolactinoma rats. This suggested that the innate immune response was activated. We analyzed the NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome that is one of the most important members of the innate immune system in mammals and found that the expressions of NLRP3, Caspase-1, apoptosis-associated speck-like, interleukin 1B (IL1B) and IL18 proteins of pituitary glands in prolactinomas rats were increased considerably compared with those in control rats. This suggested the activation of the NLRP3 inflammasome during the emergence and evolution of prolactinomas. Immunohistochemistry results also confirmed that the NLRP3 expression was elevated in human prolactinoma tissues, and the microglia marker-ionised calcium binding adaptor molecule-1 was co-located with the NLRP3 protein in prolactinomas by immunofluorescence assay. Finally, compared with the WT mice, NLRP3-/- mice had smaller pituitary glands (weight/body weight) and diminished prolactin (PRL) expressions and secretions. These findings were associated with a reduction in the caspase-1 activation and maturation of IL1B. Furthermore, MCC950 decreased the PRL expression and secretion following the inhibition of NLRP3 inflammasome activation in GH3 cells stimulated with lipopolysaccharide and nigericin. And MCC950 inhibited the pituitary tumor overgrowth and PRL expression and secretion in prolactinoma rats. These data confirm that the microglial NLRP3 inflammasome activation upregulates the inflammatory cytokines IL1/IL18 in the pituitary glands and induces prolactinomas. Our findings showed that microglial NLRP3 inflammasome activation-mediated IL1B-related inflammation promoted the development of prolactinomas and identified the inflammasome as a new therapeutic target for prolactinomas.


Assuntos
Neoplasias Hipofisárias , Prolactinoma , Animais , Caspases/metabolismo , Humanos , Inflamassomos/genética , Inflamassomos/metabolismo , Inflamação/metabolismo , Interleucina-18/metabolismo , Mamíferos/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos Transgênicos , Microglia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neoplasias Hipofisárias/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prolactinoma/metabolismo , Ratos
16.
Artigo em Inglês | MEDLINE | ID: mdl-32382283

RESUMO

Prolactinomas are harmful to human health, and the clinical first-line treatment drug is bromocriptine. However, 20% prolactinomas patients did not respond to bromocriptine. Hordenine is an alkaloid separated from Fructus Hordei Germinatus, which showed significant antihyperprolactinemia activity in rats. The aim of this study was to explore the effect and mechanism of hordenine on prolactinomas in rats. The study used estradiol to induce prolactinomas, which caused the activation of the pituitary mitogen-activated protein kinase (MAPK) pathway in rats significantly. The treatment of hordenine restored estradiol, induced the overgrowth of pituitary gland, and reduced the prolactin (PRL) accumulation in the serum and pituitary gland of rats by blocking the MAPK (p38, ERK1/2, and JNK) activation and production of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). The antiprolactinoma effect of hordenine was mediated by inhibiting the MAPK signaling pathway activation in rats.

17.
Cardiovasc Ther ; 2020: 7172052, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042224

RESUMO

BACKGROUND: We provide an updated meta-analysis with detailed information on a combination of TCM and routine treatment. METHODS: Retrieve appropriate articles with no language restrictions on keywords until 8 July 2019 in an electronic database. All trajectories are screened according to certain criteria. The quality of certified research was also evaluated. We made a detailed record of the results of the measurement. Meta-analysis was carried out by using the Revman 5.3 software. RESULTS: Sixty-seven RCTs were included, and 6594 subjects were analyzed. Compared with routine treatment, the total effective rate (TER) of TCM combined with routine treatment was improved, and the recovery of stroke was also significantly accelerated. Regulation of blood lipids by notably shrinking the contents of TC, TG, and LDL and enhancing the levels of HDL. The levels of serum hs-CRP, WHV, and WLV decreased significantly, indicating that the expression of thrombomodulin was decreased after the comprehensive treatment of traditional Chinese medicines (TCMs). The combination of TCM treatment could enhance the protection of neural function by decreasing the NIHSS scoring while increasing the BI scoring. Paeoniae Radix Rubra, Angeticae Sinensis Radix, etc., can effectively improve the clinical symptoms of stroke convalescent patients and promote the recovery of neurological function. ACU of Baihui, Renzhong, etc., can improve the clinical rehabilitation effect of patients. However, our findings must be handled with care because of the small sample size and low quality of clinic trials cited. Other rigorous and large-scale RCTs are in need to confirm these results. CONCLUSION: A combination of TCM and routine treatment in the treatment of stroke could improve TER, and it is beneficial to the rehabilitation of patients in the recovery period of apoplexy. These effects can be mediated by a combination of several mechanisms. Nevertheless, due to the limitations of this study, these results should be handled with caution.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Reabilitação do Acidente Vascular Cerebral/efeitos adversos , Resultado do Tratamento , Adulto Jovem
18.
Hum Genet ; 122(6): 589-93, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17924146

RESUMO

Microphthalmia is a clinically and genetically heterogeneous disorder of eye development. The genetic basis of nonsyndromic microphthalmia is not yet fully understood. Previous studies indicated that disease pedigrees from different genetic backgrounds could be attributed to completely different gene loci. To investigate the etiology in a large autosomal-dominant inherited simple microphthalmia (nanophthalmia) pedigree, which is the first genetically analyzed Chinese microphthalmia pedigree, we performed a whole-genome scan using 382 micro-satellite DNA markers after the exclusion of reported candidates associated with microphthalmia. Strong evidence indicated that microphthalmia in this family was mapped to an unreported new locus on chromosome 2q. A significantly positive two-point LOD score was obtained with a maximum 3.290 at a recombination fraction of 0.00 for marker D2S2265. Subsequent haplotype analysis and recombination data further confined the disease-causing gene to a 15-cM interval between D2S1890 and D2S347 on 2q11-14. Our results further underlined the degree of heterogeneity in microphthalmia from Chinese background and localized a novel gene which regulates eye embryogenesis.


Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 2 , Microftalmia/genética , Família , Feminino , Ligação Genética , Haplótipos , Humanos , Escore Lod , Masculino , Linhagem , Recombinação Genética
19.
Zhonghua Nan Ke Xue ; 9(8): 601-3, 2003 Nov.
Artigo em Zh | MEDLINE | ID: mdl-14689896

RESUMO

OBJECTIVE: To detect succinate dehydrogenase (SDH) of sperm mitochondria by an improved method, and to evaluate the relationship between SDH and the motility and viability of sperm. METHODS: In 46 fertile and infertile men (aged from 25 to 36), the motility, viability and mitochondrial SDH of sperm were detected by computer-assisted semen analysis system, dead/live sperm molecular fluorescent probe and an improved cytochemical method. Then, the correlation between the motility and viability of sperm and the positive percentage of sperm mitochondrial SDH were analyzed. RESULTS: In the 46 fertile and infertile men, the motility and viability of sperm were (67.33 +/- 7.37)% and (79.78 +/- 7.65)%, and the positive percentage of sperm mitochondrial SDH was (74.74 +/- 8.29)%. The motility and viability of sperm and positive percentage of sperm mitochondrial SDH had significant correlation (r = 0.901, P < 0.01; r = 0.876, P < 0.01; r = 0.917, P < 0.01). CONCLUSIONS: Detection of sperm mitochondrial SDH has significance in evaluation of sperm mitochondrial function and may serve as an assisted marker of sperm viability.


Assuntos
Mitocôndrias/enzimologia , Motilidade dos Espermatozoides , Espermatozoides/enzimologia , Succinato Desidrogenase/metabolismo , Adulto , Estudos de Casos e Controles , Sobrevivência Celular , Humanos , Processamento de Imagem Assistida por Computador , Infertilidade Masculina/enzimologia , Masculino
20.
Front Biosci (Landmark Ed) ; 18(3): 901-8, 2013 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-23747855

RESUMO

SDD17, a delta-15 desaturase from the fungus Saprolegnia can convert arachidonic acid to eicosapentanoic acid in yeast, plant embryos, and mammalian cells. Here, we generated transgenic mice that carried two copies of codon-optimized sdd17 cDNA within a non-coding domain of chromosome 6. RT-PCR analysis revealed that the foreign gene was expressed in the transgenic tissues. Gas chromatography showed that the levels of total unsaturated fatty acids in muscle, liver, and spleen tissues were significantly (p<0.05) increased in transgenic mice compared to non-transgenic mice at 3 or 8 weeks of age. In addition, the serum concentrations of total cholesterol and low-density lipoprotein cholesterol in transgenic females, but not in males, were significantly lower than those in sex-matched non-transgenic mice. These results suggest that endogenous sdd17 expression is beneficial for mammalian health and that its effects on fatty acid profiles may differ between sexes.


Assuntos
LDL-Colesterol/metabolismo , Colesterol/metabolismo , Ácidos Graxos Dessaturases/fisiologia , Ácidos Graxos/metabolismo , Animais , Cromatografia Gasosa , Ácidos Graxos Dessaturases/genética , Camundongos , Camundongos Transgênicos , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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