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1.
Biosens Bioelectron ; 170: 112662, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33032198

RESUMO

Cancer cell enumeration and phenotyping can predict the prognosis and the therapy efficacy in patients, yet it remains challenging to detect the rare tumor cells. Herein, we report an octopus-inspired, bifunctional aptamer signal amplifier-based cytosensor (OApt-cytosensor) for sensitive cell analysis. By assembling high-affinity antibodies on an electrode surface, the target cells could be specifically captured and thus been sandwiched by the cell surface marker-specific DNA aptamers. These on-cell aptamers function as electrochemical signal amplifiers by base-selective electronic doping with methylene blue. Such a sandwich configuration enables highly sensitive cell detection down to 10 cells/mL (equal to ~1-2 cells at a sampling volume of 150 µL), even in a large excess of nontarget blood cells. This approach also reveals the cell-surface markers and tracks the cellular epithelial-to-mesenchymal transition induced by signaling regulators. Furthermore, the electron-doped aptamer shows remarkable cell fluorescent labeling that guides the release of the captured cells from electrode surface via electrochemistry. These features make OApt-cytosensor a promising tool in revealing the heterogeneous cancer cells and anticancer drug screening at the single-cell level.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33062027

RESUMO

Acupuncture has been widely used for obesity treatment, but its mechanism is still unclear. To investigate the molecular mechanisms, we applied electroacupuncture (EA) at the Zusanli (ST36) acupoint and treadmill exercise (TE) in a diet-induced obese (DIO) rat model and used RNA sequencing (RNA-seq) to identify molecular consequences. Forty Sprague-Dawley male rats were selected and randomly divided into five groups: control (C), DIO model (M), EA, TE, and EA + TE groups. According to the results, acupuncture reduced body weight and the ratio of retroperitoneal white adipose tissue (retro-WAT) to body weight. Total RNA was extracted from the retro-WAT from five groups for RNA-seq. Differentially expressed genes (DEG) analysis showed that there were obvious differences among the four comparisons of C vs. M, M vs. EA, M vs. TE, and M vs. EA + TE, followed by 1383, 913, 3324, and 2794 DE genes. Gene ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to further classify the DEGs. Several GO terms were commonly significantly enriched in both M vs. TE and M vs. EA, such as myofibril and muscle contraction. In addition, some pathways were regulated by EA and TE, such as the peroxisome proliferator activated receptor signaling pathway and calcium signaling pathway. This study is the first to compare and analyze the differences in gene expression profiles in the retro-WAT of rats in different groups, which provide a clue for further investigation into the molecular mechanisms of obesity treatment by EA and TE.

3.
J Mater Chem B ; 8(17): 3801-3813, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32227025

RESUMO

Lack of sufficient tumor penetration of the current nanomedicines is a major reason limiting their clinical success in cancer therapy. In this work, we aimed at the development of a novel biodegradable nanoplatform for the selective and controlled delivery of anticancer agents, with improved tumor permeability and the ability to release ultrasmall nanovesicles in the tumor microenvironment. To this end, positively charged nanogels were obtained through the double-crosslinking of chitosan with an ionic physical gelator and a disulfide-containing chemical crosslinker. After conjugation to an anionic oligomer, the cationic nanogels were transformed into negatively charged nanocarriers (CTCP), enabling effective encapsulation of the cationic anticancer agent doxorubicin (DOX) to generate a biodegradable nanomedicine (DOX@CTCP). DOX@CTCP could maintain sustained DOX release and decreased DOX toxicity. Upon arrival at the tumor tissue, the reductive and lysozyme-high microenvironment drives the cleavage of the nanomedicine to release DOX-carrying nanoblocks of smaller size, which together with their acidic-protonable feature achieves an effective therapeutic delivery into cancer cells. The nanomedicine described here showed excellent biocompatibility/biosafety and enhanced in vivo antitumor efficacy.

4.
J Cell Biochem ; 121(2): 1504-1513, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31498486

RESUMO

MicroRNA-96 (miR-96) is a vertebrate conserved microRNA which plays important roles in various cancers including renal cell carcinoma (RCC). However, its function and mechanism in RCC are still unclear. In this study, miR-96 was found to be downregulated in RCC based on The Cancer Genome Atlas datasets analyses, and its target genes, which predicted by TargetScan, were investigated. Among these target genes, neuronal pentraxin 2 (NPTX2) was upregulated more than 15-fold in RCC, and moreover, closely related to patient survival. To validate its targeting of NPTX2 experimentally, reverse transcription polymerase chain reaction, Western blot analysis, and dual-luciferase assays were performed, and results of these assays demonstrated that miR-96 inhibited expression of NPTX2 through a single 3'-untranslated region targeting site. Furthermore, transfection assays in RenCa and 786-O cells showed miR-96 and small interfering RNA of NPTX2 inhibited cell proliferation, migration, and invasion and overexpression of NPTX2 recovered the inhibition of miR-96. In conclusion, the present study reveals a novel regulatory mechanism of miR-96 on NPTX2 expression in RCC, and the potential of miR-96 as a RCC tumor repressor deserves further investigation.

5.
Onco Targets Ther ; 12: 10917-10930, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31849495

RESUMO

Purpose: Natural triterpenoid saponins isolated from Anemone flaccida Fr. Schmidt have exhibited anti-cancer properties and exerted remarkable inhibitory effects on tumor growth. Herein, we investigated the potential mechanism involved in the suppression of hepatocellular carcinoma (HCC) development by triterpenoid saponins in a mouse model. Methods: An HCC model was established in H22 tumor-bearing mice and triterpenoid saponins were administered at various doses. Immunofluorescence, flow cytometry, and western blot were performed to analyze the effect of triterpenoid saponins on immune response in tumor tissues. Metabolomic analysis was carried out to assess the metabolites involved in mediating the effect of triterpenoid saponins on tumor tissues. Results: Triterpenoid saponins induced anti-tumor immune response by decreasing the number of Treg cells, increasing that of B cells, natural killer cells, and CD3+/CD28+ T cells, and reducing the secretion of inflammatory factors including nuclear factor-κB, cyclooxygenase-2, and microsomal prostaglandin E synthase-1. In addition, triterpenoid saponins inhibited tumor growth and induced the apoptosis of HCC cells by blocking the activation of PD1/PD-L1, ERK1/2, p38 MAPK, JNK, and STAT3 signaling pathways. Furthermore, triterpenoid saponins regulated tumor immune response by upregulating a number of metabolites (including 1,3-diaminopropane, lauric acid, 2,4-diaminobutyric acid 2, and ribitol) and modulating the metabolism of histidine, arginine, proline, beta-alanine, glycine, serine, and threonine. Conclusion: The findings suggested that triterpenoid saponins interfered with multiple signaling cascades involved in tumorigenesis and tumor metabolism and have potential applications in HCC therapy.

6.
Zhen Ci Yan Jiu ; 44(7): 476-80, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31368276

RESUMO

OBJECTIVE: To investigate the effect of electroacupuncture (EA) plus treadmill exercise on the expression of peroxisome proliferator activated receptor γ coactivator 1α(PGC-1α), Irisin, AMP-activated protein kinase (AMPK) in skeletal muscle of diet-induced obesity (DIO) rats, so as to explore its mechanism underlying body reduction promotion. METHODS: Forty-two male SD rats were divided into normal diet (control, n=10), high fat diet (model), EA, treadmill exercise and EA plus treadmill exercise (combination) groups (n=8 in each of the latter 4 groups). The obesity model was established by feeding the rats with high fat diet. EA (2 Hz/15 Hz, 1 mA) was applied to bilateral "Zusanli" (ST36) and "Tianshu" (ST25) for 30 min, 5 times per week for a total of 8 weeks. Rats of the treadmill exercise group were forced to perform exercise on a treadmill (16 m/min) for 30 min, 5 times per week for a total of 8 weeks. Rats in the combination group received the above-mentioned two methods. During the treatment, rats in the control group were fed with normal fodder, rats in other groups were fed with high fat fodder, and their body weight was measured once a week. The expression levels of PGC-1α, fibronectin type Ⅲ domain containing 5 (FNDC5), AMPK mRNA and protein of skeletal muscle were measured by quantitative real-time PCR and Western blot,respectively. RESULTS: After modeling, the body weight was significantly increased (P<0.05), and the expression levels of PGC-1α and FNDC5 mRNA and protein, AMPK mRNA and phosphorylated AMPK (p-AMPK) protein in the skeletal muscle were considerably decreased in the model group relevant to the control group (P<0.05). Following the treatment, the body weight was significantly down-regulated, while the expression levels of PGC-1α and FNDC5 mRNAs and proteins, AMPK mRNA and p-AMPK protein were obviously up-regulated in the EA, treadmill exercise and combination groups relevant to the model group (P<0.05). The therapeutic effect of EA plus treadmill exercise was significantly superior to those of both simple EA and simple treadmill exercise in down-regulating the body weight, as well as in up-regulating the expression of PGC-1α and FNDC5 mRNAs and proteins, AMPK mRNA, and p-AMPK protein (P<0.05). CONCLUSION: Both EA and treadmill exercise can significantly increase the expression of PGC-1α, FNDC5 and p-AMPK in skeletal muscle of DIO rats, suggesting their efficacy in restoring fatty acid oxidation in skeletal muscle cells and improving mitochondrial function, which may contribute to their function in body reduction. The therapeutic effect of EA plus treadmill exercise is better than that of simple EA and simple treadmill exercise.


Assuntos
Eletroacupuntura , Proteínas Quinases Ativadas por AMP , Animais , Peso Corporal , Fibronectinas , Humanos , Masculino , Músculo Esquelético , Obesidade , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Ratos , Ratos Sprague-Dawley
7.
Chin J Nat Med ; 17(2): 131-144, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30797419

RESUMO

Anemone flaccida Fr. Schmidt is a perennial medicinal herb that contains pentacyclic triterpenoid saponins as the major bioactive constituents. In China, the rhizomes are used as treatments for a variety of ailments including arthritis. However, yields of the saponins are low, and little is known about the plant's genetic background or phytohormonal responsiveness. Using one-quarter of the 454 pyrosequencing information from the Roche GS FLX Titanium platform, we performed a transcriptomic analysis to identify 157 genes putatively encoding 26 enzymes involved in the synthesis of the bioactive compounds. It was revealed that there are two biosynthetic pathways of triterpene saponins in A. flaccida. One pathway depends on ß-amyrin synthase and is similar to that found in other plants. The second, subsidiary ("backburner") pathway is catalyzed by camelliol C synthase and yields ß-amyrin as minor byproduct. Both pathways used cytochrome P450-dependent monooxygenases (CYPs) and family 1 uridine diphosphate glycosyltransferases (UGTs) to modify the triterpenoid backbone. The expression of CYPs and UGTs were quite different in roots treated with the phytohormones methyl jasmonate, salicylic acid and indole-3-acetic acid. This study provides the first large-scale transcriptional dataset for the biosynthetic pathways of triterpene saponins and their phytohormonal responsiveness in the genus Anemone.


Assuntos
Anemone/genética , Vias Biossintéticas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Reguladores de Crescimento de Planta/farmacologia , Saponinas/metabolismo , Triterpenos/metabolismo , Anemone/efeitos dos fármacos , Anemone/metabolismo , Vias Biossintéticas/genética , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Perfilação da Expressão Gênica , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Medicinais , Rizoma/efeitos dos fármacos , Rizoma/genética , Rizoma/metabolismo
8.
Artigo em Inglês | MEDLINE | ID: mdl-30363899

RESUMO

Obesity is a worldwide public health problem. Currently, increasing evidence suggests acupuncture and related therapies are effective for obesity. This network meta-analysis (NMA) was performed to compare the effectiveness of different acupuncture and related therapies. We searched potential randomized controlled trials (RCTs) in three international databases. Thirty-four trials involving 2283 participants were included. Pairwise meta-analysis showed that acupuncture and related therapies were superior to lifestyle modification and placebo in reducing weight and body mass index (BMI). Based on decreases in body weight, results from NMA showed that acupoint catgut embedding (standard mean difference [SMD]: 1.26; 95% credible interval [95% CI], 0.46-2.06), acupuncture (SMD: 2.72; 95% CrI, 0.06-5.29), and combination of acupuncture and related theories (SMD: 3.65; 95% CrI, 0.96-6.94) were more effective than placebo. Another NMA result indicated that acupoint catgut embedding (SMD: 0.63; 95% CI, 0.25-1.11), acupuncture (SMD: 1.28; 95% CrI, 0.43-2.06), combination of acupuncture and related therapies (SMD: 1.44; 95% CrI, 0.64-2.38), and electroacupuncture (SMD: 0.60; 95% CrI, 0.03-1.22) were superior to lifestyle modification in decreasing BMI. Combination of acupuncture and related therapies was ranked the optimal method for both reducing weight and BMI. Further studies will clarify which combination of acupuncture and related therapies is better.

9.
Oncol Lett ; 15(6): 8945-8950, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29844814

RESUMO

The present study aimed to observe the expression of circadian gene clock circadian regulator (CLOCK) in ovarian cancer cells and the effects of circadian gene CLOCK on cis-dichlorodiamine platinum (cisplatin) resistance in ovarian cancer cells. The expression of CLOCK mRNA and protein in cisplatin-sensitive A2780 and cisplatin-resistant CP70 cells were detected by quantitative polymerase chain reaction and western blot assay. Cisplatin-sensitive A2780 and cisplatin-resistant CP70 cells were treated with different concentrations of cisplatin for 48 h, and the expression of hCLOCK protein in the two types of cells was detected by western blot assay. RNA interference method was used to knock down the expression of CLOCK in cisplatin-resistant CP70 cells. Subsequently, the cisplatin-resistant CP70 cells were treated with cisplatin. The proliferation of cisplatin-resistant CP70 cells was observed following treatment with cisplatin. The expression of CLOCK mRNA was significantly higher in cisplatin-resistant CP70 cells (1.58±0.49) compared with cisplatin-sensitive A2780 cells (0.44±0.13) (P<0.01). Western blot assay results demonstrated that the expression of CLOCK protein was significantly greater in the cisplatin-resistant CP70 cells (1.47±0.34) compared with the cisplatin-sensitive A2780 cells (0.48±0.15) (P<0.01). Following the treatment of A2780 and CP70 cells with cisplatin, CLOCK protein expression increased with an increased concentration of cisplatin, in a dose-dependent manner (P<0.01). Following the knockdown of CLOCK in cisplatin-resistant CP70 cells by RNA interference, cisplatin treatment was able to significantly inhibit the proliferation of cells and induce apoptosis (P<0.01). The expression of circadian gene CLOCK in ovarian cancer cells was strongly associated with cisplatin resistance. The upregulation of circadian gene CLOCK in ovarian cancer cells may reduce its sensitivity to cisplatin treatment.

10.
Am J Transl Res ; 9(3): 1203-1212, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28386346

RESUMO

Chemotherapy has improved the clinical outcomes of cervical cancer patients. However, patients develop chemoresistance, whose underlying mechanisms are not well understood. In this study, we investigated the phosphorylation levels of eukaryotic translation initiation factor 4E (eIF4E) in cervical cancer cells subjected to chemotherapy. Results showed that chemotherapeutic drugs significantly increased eIF4E phosphorylation at S209 in HeLa and SiHa cells. Upregulation of phosphorylated eIF4E (p-eIF4E) levels has also been shown in cisplatin-resistant HeLa cells and has been observed to be a common response of cervical cancer patients undergoing chemotherapy. We further showed that chemotherapeutic drugs increase ß-catenin activity and mRNA levels of Wnt/ß-catenin target genes in cervical cancer cells but not in eIF4E-depleted cells, suggesting that chemotherapeutic drugs activate Wnt/ß-catenin signaling in an eIF4E-dependent manner. Inhibiting eIF4E via siRNA knockdown or Wnt/ß-catenin using the Wnt inhibitor pyrvinium effectively enhanced the anti-proliferative and pro-apoptotic effects of cisplatin in cervical cancer cells both in vitro and in vivo. Our findings demonstrate that eIF4E/ß-catenin signaling plays a positive regulatory role in the resistance of cervical cancer cell to chemotherapy and thus highlight the therapeutic value of eIF4E or ß-catenin inhibition in overcoming chemoresistance.

11.
Onco Targets Ther ; 9: 1969-79, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27103823

RESUMO

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft tissue neoplasms that are extremely rare and are frequently associated with neurofibromatosis type 1 patients. MPNSTs are typically fatal, and there is no effective treatment so far. In our previous study, we showed that flaccidoside II, one of the triterpenoid saponins isolated from Anemone flaccida Fr. Schmidt, has antitumor potential by inducing apoptosis. In the present study, we found that flaccidoside II inhibits proliferation and facilitates apoptosis in MPNST cell lines ST88-14 and S462. Furthermore, this study provides a mechanism by which the downregulation of heme oxygenase-1 via extracellular signal-regulated kinase-1/2 and p38 mitogen-activated protein kinase pathways is involved in the apoptotic role of flaccidoside II. This study suggested the potential of flaccidoside II as a novel pharmacotherapeutic approach for MPNSTs.

12.
PLoS One ; 9(11): e112400, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25383945

RESUMO

The retinal pigment epithelium-specific 65 kDa protein is an isomerase encoded by the RPE65 gene (MIM 180069) that is responsible for an essential enzymatic step required for the function of the visual cycle. Mutations in the RPE65 gene cause not only subtype II of Leber congenital amaurosis (LCA) but also early-onset severe retinal dystrophy (EOSRD). This study aims to investigate a Chinese case diagnosed as EOSRD and to characterize the polymorphisms of the RPE65 gene. A seven-year-old girl with clinical symptoms of EOSRD and her parents were recruited into this study. Ophthalmologic examinations, including best-corrected visual acuity, slit-lamp, Optical coherence tomography (OCT), and fundus examination with dilated pupils, were performed to determine the clinical characteristics of the whole family. We amplified and sequenced the entire coding region and adjacent intronic sequences of the coding regions of the RPE65 gene for the whole family to explore the possible mutation. Our results demonstrate that the patient exhibited the typical clinically features of EOSRD. Her bilateral decimal visual acuity was 0.3 and 0.4 in the left and right eyes, respectively. Spectral-domain optical coherence tomography (SD-OCT) was used to assess the retinal stratification for the whole family. All together, we identified four mutations within the RPE65 gene (c.1056G>A, c.1243+2T>A, c.1338+20A>C and c.1590C>A) in the patient. Among the four mutations, c.1056G>A and c.1338+20A>C had been reported previously and another two were found for the first time in this study. Her mother also carried the novel mutation (c.1243+2T>A). Either a single or a compound heterozygous or a homozygous one mutation is expected to cause EOSRD because mutations of RPE65 gene usually cause an autosomal recessive disease. Therefore, we speculate that the c.1590C>A mutation together with the c.1243+2T>A mutation may cause the patient's phenotype.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Amaurose Congênita de Leber/genética , Amaurose Congênita de Leber/patologia , Polimorfismo de Nucleotídeo Único , cis-trans-Isomerases/genética , Criança , China , Feminino , Estudos de Associação Genética , Células HEK293 , Humanos , Técnicas In Vitro , Masculino , Linhagem , RNA Mensageiro/metabolismo , Análise de Sequência de DNA
13.
Int Ophthalmol ; 33(3): 269-76, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23242590

RESUMO

Bietti crystalline corneoretinal dystrophy (BCD, MIM 210370) is a type of hereditary retinal disorder which commonly occurs in China. It is known that mutations in the CYP4V2 gene result in BCD. The purpose of this study was to investigate the case of a Chinese family and characterize the polymorphisms of the CYP4V2 gene. A 29-year-old male (the son of a Chinese family) with typical clinical symptoms of BCD and his family were recruited into this study. Ophthalmologic examination, including best-corrected visual acuity, slit-lamp, and fundus examination with dilated pupils, was conducted to determine the clinical characteristics of the whole family. The entire coding region and adjacent intronic sequences of 11 coding regions of the CYP4V2 gene of the whole family were then amplified by polymerase chain reaction and sequenced. Our results show that the son had typical clinical features of BCD. His bilateral decimal visual acuity was 0.06 (left eye) and 0.01 (right eye). Bilateral crystal-like deposits were found in the posterior pole of his fundus, and differing extent of atrophy of the retinal pigment epithelium, and carpet-like retinal degeneration along with numerous tiny glittering crystals were also clearly observed. However, such characteristics were not found on the fundus of his parents' eyes. Five mutations within the CYP4V2 gene (c.64C>G, c.775C>A, c.810T>G, c.1091-2A>G, and c.1399T>C) were identified in the son. Among the five mutations, four had previously been reported and the c.1399T>C was discovered for the first time. This novel mutation causes an amino acid substitution (C467R) in the CYP4V2 protein, but it was not detected in the parents. As there is no apparent relationship in genotype-phenotype correlation between the CYP4V2 gene and the occurrence of BCD, this novel mutation may be a possible cause that could induce the clinical phenotype of BCD.


Assuntos
Distrofias Hereditárias da Córnea/genética , Sistema Enzimático do Citocromo P-450/genética , Mutação , Doenças Retinianas/genética , Adulto , Substituição de Aminoácidos , Grupo com Ancestrais do Continente Asiático , China , Distrofias Hereditárias da Córnea/patologia , Família 4 do Citocromo P450 , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Fenótipo , Doenças Retinianas/patologia
14.
Zhong Yao Cai ; 28(7): 541-3, 2005 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-16252719

RESUMO

The pharmacognosy of Taraphochlamys affinis (Giff) Bremekhu was studied by microscopic observation to provide a scientific basis for the identification, development and utilization of its resources. As a result, obvious characteristics for its identification were revealed, which could be used to identify twigs and leaves of Taraphochlamys affinis (Giff) Bremekhu.


Assuntos
Acanthaceae/anatomia & histologia , Plantas Medicinais/anatomia & histologia , Acanthaceae/citologia , Farmacognosia , Epiderme Vegetal/anatomia & histologia , Epiderme Vegetal/citologia , Folhas de Planta/anatomia & histologia , Folhas de Planta/citologia , Caules de Planta/anatomia & histologia , Caules de Planta/citologia , Plantas Medicinais/citologia
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