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1.
Dalton Trans ; 53(21): 8980-8987, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38717188

RESUMO

Octanuclear polyoxomolybdenum-based porous materials, Na8[Mo8O8(µ2-O)8(µ2-OH)8(3-apz)4]2·26H2O (1, 3-Hapz = 3-aminopyrazole), K8[Mo8O8(µ2-O)8(µ2-OH)8(3-apz)4]2·7H2O (2) and (NH4)4[Mo8O8(µ2-O)8(µ2-OH)4(3-apz)8]·20.5H2O (3), have been successfully synthesized by a hydrothermal method and fully characterized. X-ray structural analyses show that microporous materials 1-3 contain round pores formed by octanuclear molybdenum-oxygen groups connected sequentially with pore sizes of 4.0, 4.0, and 4.8 Å, respectively. Both 1 and 2 are composed of two {Mo8} rings, which are connected by strong intramolecular hydrogen bonds between bridging hydroxy groups and oxygen atoms to form dimeric structures. The central pores in 1 and 2 are occupied by Na+ and K+, respectively, while they are empty in 3. This reflects the structural expansion and contraction effects induced by different cations. Through intermolecular stacking, 1-3 also exhibit channels with sizes of 14.0 × 6.4, 4.6 × 2.6, and 5.4 × 5.4 Å, respectively, which were used for the studies of gas adsorption. The results show that 1-3 can selectively adsorb CO2 and O2, including the empty hole in 3, while they show little or no affinity for gases H2, N2, and CH4. Moreover, an additional polyoxomolybdenum-based species (Mo8O26)n·4n(3-H2apz) (4) has been obtained with protonated 3-aminopyrazole in the absence of a reducing agent, which can serve as an intermediate for the polyoxomolybdenum-based porous products.

2.
Curr Med Sci ; 44(2): 369-379, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38619683

RESUMO

OBJECTIVE: Matrix metalloproteinase 13 (MMP13) is an extracellular matrix protease that affects the progression of atherosclerotic plaques and arterial thrombi by degrading collagens, modifying protein structures and regulating inflammatory responses, but its role in deep vein thrombosis (DVT) has not been determined. The purpose of this study was to investigate the potential effects of MMP13 and MMP13-related genes on the formation of DVT. METHODS: We altered the expression level of MMP13 in vivo and conducted a transcriptome study to examine the expression and relationship between MMP13 and MMP13-related genes in a mouse model of DVT. After screening genes possibly related to MMP13 in DVT mice, the expression levels of candidate genes in human umbilical vein endothelial cells (HUVECs) and the venous wall were evaluated. The effect of MMP13 on platelet aggregation in HUVECs was investigated in vitro. RESULTS: Among the differentially expressed genes, interleukin 1 beta, podoplanin (Pdpn), and factor VIII von Willebrand factor (F8VWF) were selected for analysis in mice. When MMP13 was inhibited, the expression level of PDPN decreased significantly in vitro. In HUVECs, overexpression of MMP13 led to an increase in the expression level of PDPN and induced platelet aggregation, while transfection of PDPN-siRNA weakened the ability of MMP13 to increase platelet aggregation. CONCLUSIONS: Inhibiting the expression of MMP13 could reduce the burden of DVT in mice. The mechanism involves downregulating the expression of Pdpn through MMP13, which could provide a novel gene target for DVT diagnosis and treatment.


Assuntos
Trombose Venosa , Animais , Humanos , Camundongos , Modelos Animais de Doenças , Células Endoteliais da Veia Umbilical Humana/metabolismo , Metaloproteinase 13 da Matriz/genética , Agregação Plaquetária , Trombose Venosa/genética
3.
Front Vet Sci ; 10: 1301316, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38076558

RESUMO

Background: Small mammals serve as the main reservoir for Bartonella and as a proxy indicator of the potential risk of Bartonella transmission from nature to humans. They offer a valuable early warning for human infection. Nevertheless, geographical variations in the impact of the host on the occurrence of Bartonella infection are underestimated. This study was designed to investigate the infection characteristics of Bartonella and explore its species diversity in wild small mammals in western Yunnan Province, China. Methods: Wild small mammals were captured from Yulong, Jianchuan, and Lianghe counties in western Yunnan Province between 2015 and 2016. Real-time quantitative PCR (qPCR) was used to detect Bartonella infection, and the Bartonella species were identified by phylogenetic analysis. The factors associated with Bartonella infection in small mammals were analyzed by the Chi-square Test. Results: The prevalence of Bartonella in small mammals was 47.85% (768/1605). Lianghe County had the highest Bartonella infection rate, with 56.27% of the samples tested positive, followed by a rate of 50.91% was tested in Yulong County, and 39.97% in Jianchuan County (p < 0.001). Bartonella was detected positive in a total 25 small mammal species, with infection rates ranging from 2.17% to 100%. Niviventer fulvescens had the highest Bartonella infection rate. In comparison with the dominant small mammal species, Eothenomys mileyus had the lowest Bartonella infection rate than that in Apodemus chevrieri, Rattus tanezumi, and Apodemus draco (p < 0.001). Male small mammals had a higher infection rate than females (p < 0.05). The prevalence of Bartonella in small mammals during the summer season was higher compared to the other three seasons (p < 0.001). Woodland landscape had the highest Bartonella infection rate (p < 0.001). Bartonella rochalimae, B. japonica, B. tribocorum, B. washoensis, B. sylvatica, and B. rattimassiliensis were obtained from infected small mammals. Conclusion: This study showed a high prevalence of Bartonella was detected with various Bartonella species in small mammals in Yulong, Jianchuan, and Lianghe counties of western Yunnan Province. These findings hold significant scientific clues, providing valuable reference points for further research of Bartonella natural foci in Yunnan or other analogues environments.

4.
Pathogens ; 12(1)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36678476

RESUMO

Small mammals can transmit and serve as a reservoir for Orientia tsutsugamushi (Ot) in nature by carrying infected mites. In Yunnan, one of China's main foci of scrub typhus, etiological evidence and genetic diversity for Ot is limited. A total of 2538 small mammals were captured seasonally from 2015 to 2016 in the three counties of Yunnan, and the spleen or liver tissue was examined for Ot based on 56 kDa nPCR. The overall prevalence of Ot was 1.77%, ranging from 0.26 to 9.09% across different species. The Gilliam strain was found in 35.6% (16/45) of the wild small mammals, followed by the Karp 11.1% (5/45) and TA763 (1/45) strains, the last of which was discovered in western Yunnan for the first time. In Lianghe, Ot infection rates in wild small mammals were higher than in the other two counties. The infection rates of Eothenomys miletus with Ot were highest in the three dominant species. Ot infection rates in wild small mammals were higher in Lianghe (1200-1400 m) and Yulong (2800-3000 m). These findings could provide research clues for further confirmation of scrub typhus foci in western Yunnan or other similar natural environments.

5.
J Nanobiotechnology ; 20(1): 50, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35078498

RESUMO

BACKGROUND: Although cisplatin-based chemotherapy has been used as the first-line treatment for ovarian cancer (OC), tumor cells develop resistance to cisplatin during treatment, causing poor prognosis in OC patients. Studies have demonstrated that overactivation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is involved in tumor chemoresistance and that overexpression of microRNA-497 (miR497) may overcome OC chemotherapy resistance by inhibiting the mTOR pathway. However, the low transcriptional efficiency and unstable chemical properties of miR497 limit its clinical application. Additionally, triptolide (TP) was confirmed to possess a superior killing effect on cisplatin-resistant cell lines, partially through inhibiting the mTOR pathway. Even so, the clinical applications of TP are restricted by serious systemic toxicity and weak water solubility. RESULTS: Herein, whether the combined application of miR497 and TP could further overcome OC chemoresistance by synergically suppressing the mTOR signaling pathway was investigated. Bioinspired hybrid nanoparticles formed by the fusion of CD47-expressing tumor exosomes and cRGD-modified liposomes (miR497/TP-HENPs) were prepared to codeliver miR497 and TP. In vitro results indicated that the nanoparticles were efficiently taken up by tumor cells, thus significantly enhancing tumor cell apoptosis. Similarly, the hybrid nanoparticles were effectively enriched in the tumor areas and exerted significant anticancer activity without any negative effects in vivo. Mechanistically, they promoted dephosphorylation of the overactivated PI3K/AKT/mTOR signaling pathway, boosted reactive oxygen species (ROS) generation and upregulated the polarization of macrophages from M2 to M1 macrophages. CONCLUSION: Overall, our findings may provide a translational strategy to overcome cisplatin-resistant OC and offer a potential solution for the treatment of other cisplatin-resistant tumors.


Assuntos
Exossomos , MicroRNAs , Nanopartículas , Neoplasias Ovarianas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Diterpenos , Resistencia a Medicamentos Antineoplásicos , Compostos de Epóxi , Exossomos/metabolismo , Humanos , Lipossomos/farmacologia , MicroRNAs/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Fenantrenos , Fosfatidilinositol 3-Quinases/metabolismo
6.
PLoS One ; 16(3): e0248527, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33684177

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0238085.].

7.
PLoS One ; 16(1): e0238085, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33481789

RESUMO

Ratooning is an important cultivation practice in sugarcane production around the world, with underground buds on the remaining stalk acting as the source for establishment of a subsequent ratoon crop. However, the optimal depth of cutting during harvest in terms of yield and root growth remains unknown. We carried out a two-year field study to determine the effects of three cutting depths (0, 5 and 10 cm below the surface) ratoon cane root and yield. Results showed that cutting to a depth of 5 cm increased the root fresh weight and root volume by 21-59% and 41-127%, respectively, compared to cutting depths of 0 and 10 cm. Remarkably, cutting to a depth of 5 cm also had a significant effect on the development of fine roots, which is closely linked to cane yield. The effect was particularly noticeable in terms of two root traits, root volume and the surface area of roots with a diameter of 1.0-2.0mm, and root length and the number of root tips in roots with a diameter of 0-0.5mm. As a result, a cutting depth of 5 cm below the surface increased cane yield by 43 and 28% compared to depths of 0 and 10 cm below the surface, respectively. Overall, these findings suggest that a cutting depth of 5 cm is optimal in terms of sugarcane yield, largely due to the enhanced effect on root traits, especially the development of fine roots. These findings will help optimize sugarcane ratoon management and improve the ratoon cycle.


Assuntos
Agricultura/métodos , Raízes de Plantas/crescimento & desenvolvimento , Saccharum/crescimento & desenvolvimento , China , Raízes de Plantas/metabolismo , Saccharum/metabolismo , Solo
8.
BMC Cancer ; 20(1): 740, 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32770988

RESUMO

BACKGROUND: Precision oncology pharmacotherapy relies on precise patient-specific alterations that impact drug responses. Due to rapid advances in clinical tumor sequencing, an urgent need exists for a clinical support tool that automatically interprets sequencing results based on a structured knowledge base of alteration events associated with clinical implications. RESULTS: Here, we introduced the Oncology Pharmacotherapy Decision Support System (OncoPDSS), a web server that systematically annotates the effects of alterations on drug responses. The platform integrates actionable evidence from several well-known resources, distills drug indications from anti-cancer drug labels, and extracts cancer clinical trial data from the ClinicalTrials.gov database. A therapy-centric classification strategy was used to identify potentially effective and non-effective pharmacotherapies from user-uploaded alterations of multi-omics based on integrative evidence. For each potentially effective therapy, clinical trials with faculty information were listed to help patients and their health care providers find the most suitable one. CONCLUSIONS: OncoPDSS can serve as both an integrative knowledge base on cancer precision medicine, as well as a clinical decision support system for cancer researchers and clinical oncologists. It receives multi-omics alterations as input and interprets them into pharmacotherapy-centered information, thus helping clinicians to make clinical pharmacotherapy decisions. The OncoPDSS web server is freely accessible at https://oncopdss.capitalbiobigdata.com .


Assuntos
Bases de Dados Factuais , Sistemas de Apoio a Decisões Clínicas , Neoplasias/tratamento farmacológico , Neoplasias/genética , Medicina de Precisão , Navegador , Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Anotação de Sequência Molecular , Interface Usuário-Computador
9.
PLoS One ; 15(7): e0235845, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32639979

RESUMO

Drought is an important factor which limits growth of sugarcane. To elucidate the physiological and biochemical mechanisms of tolerance, a pot experiment was conducted at Sugarcane Research Institute, Kaiyuan, China. Two genotypes (Yuetang 93-159-sensitive and Yunzhe 05-51-tolerant), were subjected to three treatments; 70±5% (control), 50±5% (moderate drought) and 30±5% (severe drought) of soil field capacity. The results demonstrated that drought induced considerable decline in morpho-physiological, biochemical and anatomical parameters of both genotypes, with more pronounced detrimental effects on Yuetang 93-159 than on Yunzhe 05-51. Yunzhe 05-51 exhibited more tolerance by showing higher dry biomass, photosynthesis and antioxidant enzyme activities. Compared with Yuetang 93-159, Yunzhe 05-51 exhibited higher soluble sugar, soluble protein and proline contents under stress. Yunzhe 05-51 illustrated comparatively well-composed chloroplast structure under drought stress. It is concluded that the tolerance of Yunzhe 05-51 was attributed to improved antioxidant activities, osmolyte accumulation and enhanced photosynthesis. These findings may provide valuable information for future studies on molecular mechanism of tolerance.


Assuntos
Saccharum/genética , Aclimatação , Secas , Fotossíntese , Saccharum/fisiologia , Saccharum/ultraestrutura , Estresse Fisiológico
10.
Sci Rep ; 9(1): 15285, 2019 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653891

RESUMO

Two complete chloroplast genome sequences of Asteropyrum, as well as those of 25 other species from Ranunculaceae, were assembled using both Illumina and Sanger sequencing methods to address the structural variation of the cp genome and the controversial systematic position of the genus. Synteny and plastome structure were compared across the family. The cp genomes of the only two subspecies of Asteropyrum were found to be differentiated with marked sequence variation and different inverted repeat-single copy (IR-SC) borders. The plastomes of both subspecies contains 112 genes. However, the IR region of subspecies peltatum carries 27 genes, whereas that of subspecies cavaleriei has only 25 genes. Gene inversions, transpositions, and IR expansion-contraction were very commonly detected in Ranunculaceae. The plastome of Asteropyrum has the longest IR regions in the family, but has no gene inversions or transpositions. Non-coding regions of the cp genome were not ideal markers for inferring the generic relationships of the family, but they may be applied to interpret species relationship within the genus. Plastid phylogenomic analysis using complete cp genome with Bayesian method and partitioned modeling obtained a fully resolved phylogenetic framework for Ranunculaceae. Asteropyrum was detected to be sister to Caltha, and diverged early from subfamily Ranunculoideae.


Assuntos
Cloroplastos/genética , Genoma de Cloroplastos/genética , Genomas de Plastídeos/genética , Genômica/métodos , Plastídeos/genética , Ranunculaceae/genética , Teorema de Bayes , Evolução Molecular , Genes de Cloroplastos/genética , Genes de Plantas/genética , Sequências Repetidas Invertidas/genética , Filogenia , Ranunculaceae/classificação , Análise de Sequência de DNA/métodos , Especificidade da Espécie
11.
Biomed Res Int ; 2019: 2595801, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31240207

RESUMO

Triptolide has been proven to possess anticancer efficacy; however, its application in the clinical practice was limited by poor water solubility, hepatotoxicity, and nephrotoxicity. In this study, a triptolide-loaded exosomes delivery system (TP-Exos) was constructed and its effects on the proliferation and apoptosis of SKOV3 cells in vitro and in vivo were observed. SKOV3-exosomes (SK-Exos) were collected by ultracentrifugation and ultrafiltration centrifugation. TP-Exos was constructed by sonication and ultrafiltration centrifugation. SK-Exos and TP-Exos were characterized by transmission electron microscopy, western blotting, nanoparticle-tracking analysis, and high-performance liquid chromatography. Cellular uptake of exosomes, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, bromodeoxyuridine (BrdU) cell proliferation assay, and cell apoptosis experiment were used to study the effect of TP-Exos on ovarian cancer in vitro. Tumor-targeting study of exosomes, monitoring the tumor volume of mice, and TdT-mediated dUTP Nick-End labeling (TUNEL) assay were used to evaluate the effect of TP-Exos on ovarian cancer in vivo. The toxicity of TP-Exos in vivo was evaluated by liver and kidney function and histopathology of major organs (heart, liver, spleen, lung, kidney, and ovary). The results revealed that TP-Exos not only have the general characteristics of exosomes but also have high drug encapsulation efficiency. Besides, PKH26 labeled exosomes (PKH26-Exos) could be uptaken by SKOV3 cells, and Dir labeled exosomes (Dir-Exos) could be enriched to the tumor site of tumor bearing mice. Furthermore, the cytotoxic and apoptotic effects on SKOV3 cells of TP-Exos were weaker than those of free TP, and tumor cell proliferation inhibition and tumor growth inhibition were stronger than that of free TP. Moreover, TP-Exos have toxic effect on liver and spleen. In conclusion, the TP-Exos could be a promising strategy for ovarian cancer, but they need to be further optimized to attenuate the damage to liver and spleen.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diterpenos/farmacologia , Exossomos/metabolismo , Neoplasias Ovarianas/metabolismo , Fenantrenos/farmacologia , Animais , Carcinoma Epitelial do Ovário/metabolismo , Linhagem Celular Tumoral , Diterpenos/uso terapêutico , Sistemas de Liberação de Medicamentos , Compostos de Epóxi/farmacologia , Compostos de Epóxi/uso terapêutico , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Ovário , Fenantrenos/uso terapêutico , Coelhos , Testes de Toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Theranostics ; 9(4): 1047-1065, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30867815

RESUMO

Background: Platinum (II) (Pt(II))-based anticancer drugs dominate the chemotherapy field of ovarian cancer. However, the patient's quality of life has severely limited owing to dose-limiting toxicities and the advanced disease at the time of diagnosis. Multifunctional tumor-targeted nanosized ultrasound contrast agents (glutathione (GSH)-sensitive platinum (IV) (Pt(IV)) prodrug-loaded phase-transitional nanoparticles, Pt(IV) NP-cRGD) were developed for precise theranostics against ovarian cancer. Methods: Pt(IV) NP-cRGD were composed of a perfluorohexane (PFH) liquid core, a hybrid lipid-polymer shell with PLGA12k-PEG2k and DSPE-PEG1k-Pt(IV), and an active targeting ligand, the cRGD peptide (PLGA: poly(lactic-co-glycolic acid), PEG: polyethylene glycol, DSPE: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, cRGD: cyclic Arg-Gly-Asp). Pt(IV), a popular alternative to Pt(II), was covalently attached to DSPE-PEG1k to form the prodrug, which fine-tuned lipophilicity and improved cellular uptake. The potential of Pt(IV) NP-cRGD as contrast agents for ultrasound (US) imaging was assessed in vitro and in vivo. Moreover, studies on the antitumor efficiency and antitumor mechanism of Pt(IV) NP-cRGD assisted by US were carried out. Results: Pt(IV) NP-cRGD exhibited strong echogenic signals and excellent echo persistence under an US field. In addition, the GSH-sensitive and US-triggered drug delivery system maximized the therapeutic effect while reducing the toxicity of chemotherapy. The mechanistic studies confirmed that Pt(IV) NP-cRGD with US consumed GSH and enhanced reactive oxy gen species (ROS) levels, which further causes mitochondria-mediated apoptosis. Conclusion: A multifunctional nanoplatform based on phase-transitional Pt(IV) NP-cRGD with US exhibited excellent echogenic signals, brilliant therapeutic efficacy and limited side effect, suggesting precise theranostics against ovarian cancer.


Assuntos
Antineoplásicos/administração & dosagem , Terapia de Alvo Molecular/métodos , Nanocompostos/administração & dosagem , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/tratamento farmacológico , Compostos de Platina/administração & dosagem , Ultrassonografia/métodos , Animais , Meios de Contraste/administração & dosagem , Modelos Animais de Doenças , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Feminino , Lipídeos/administração & dosagem , Camundongos Nus , Nanocompostos/química , Transplante de Neoplasias , Peptídeos Cíclicos/administração & dosagem , Polímeros/administração & dosagem , Pró-Fármacos/administração & dosagem , Nanomedicina Teranóstica/métodos , Transplante Heterólogo , Resultado do Tratamento
13.
PhytoKeys ; (117): 133-142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30804700

RESUMO

Clematismae Z.Z.Yang & L.Xie, a new species of Ranunculaceae from Xinjiang, China, is described and illustrated. The new species is morphologically similar to C.orientalis and C.glauca but can be distinguished for being a less hairy plant (hairy in C.orientalis), often 2-ternate leaves (1-2-pinnate for C.orientalis and C.glauca), lanceolate to linear-lanceolate leaflets (elliptic or ovate in C.glauca), larger flowers (smaller flower in C.orientalis) and narrowly lanceolate sepals with acute to slightly attenuate apex (narrowly oblong sepals in C.orientalis and ovate to broadly lanceolate sepals in C.glauca). The new species is endemic to the southern slope of North Tianshan Mountain in Central Xinjiang. The conservation status of the species is also discussed.

14.
Yi Chuan ; 41(1): 18-27, 2019 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-30686782

RESUMO

Gene editing technologies are used to specifically edit the target sequence. With the development of zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), regular clustering of short palindrome repeats (CRISPR) and single base editing (BE) techniques, gene editing technologies not only provide powerful tools for gene functional studies, but also offer new therapeutic strategies in biomedical research. Gene editing has demonstrated broad application prospects in the gene therapy field, as well as in the construction of animal and cell models, drug target screening and gene functional research. In this review, we summarize several typical gene editing technologies, their characteristics and applications in gene therapy and discusses their opportunities and challenges in gene therapy, thereby providing critical insights and references on the clinical application of gene editing technologies.


Assuntos
Edição de Genes , Terapia Genética , Animais , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Endonucleases/genética , Humanos , Pesquisa , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/genética
15.
Yi Chuan ; 40(11): 998-1006, 2018 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-30465532

RESUMO

Krüppel-like factors (KLFs) regulate diverse physiological processes such as the differentiation and development of red blood cells. However, it remains unclear whether KLFs exhibit synergistic regulatory effects. Transcriptomic data from our previous study showed that KLF1 and KLF9 expression was significantly higher in differentiated red blood cells than in hematopoietic stem cells. In the present study, we manipulated KLF1 and KLP9 gene expression by overexpressing or knocking down KLF1 and KLF9 in K562 cells and revealed a positive correlation between the expression of KLF1 and KLF9; their co-expression can significantly promote erythroid differentiation and specifically enhance ß-globin gene expression. Further, we analyzed the transcriptome data of K562 cells with altered KLF1/KLF9 levels and found that KLF1 and KLF9 synergistically regulated erythroid differentiation through the PI3K-Akt and FoxO signaling pathways. KLF1 and KLF9 may exert this synergistic effect through FOS, TF, and IL8 in K562 cells. We have provided evidence that KLF1 and KLF9 play a synergistic role in regulating erythroid differentiation.


Assuntos
Eritrócitos/citologia , Eritropoese , Fatores de Transcrição Kruppel-Like/metabolismo , Eritrócitos/metabolismo , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Células K562 , Fatores de Transcrição Kruppel-Like/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
16.
J Biomed Nanotechnol ; 14(10): 1761-1772, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30041722

RESUMO

Triptolide has proven to possess anticancer potential and been widely used for anti-cancer research. However, the liver and kidney toxicity has limited its application in cancer treatment. In this study, a drug delivery system based on mPEG-DPPE/calcium phosphate was developed to co-load triptolide and curcumin (TP and Curc-NPs). The coefficient of drug interaction (CDI) was calculated to determine the optimal concentration of the two drugs. When the concentration of triptolide was 25.22 ng/mL and the concentration of curcumin was 6.62 µg/mL, the two drugs reached the maximum synergistic killing effects on SKOV-3 tumor cells. The TP and Curc-NPs was prepared using ultrasonic emulsification. Flow cytometry results revealed that the TP and Curc-NPs arrested cell-cycle in the S and G2/M phases and exhibited a strong ability to induce apoptosis. Intracellular reactive oxygen species (ROS) results indicated that curcumin could reduce the intracellular ROS level caused by triptolide. The mRNA levels of heat shock protein (HSP) were detected by qTR-PCR and the results showed that the TP and Curc-NPs could lower the HSP70 mRNA level while could not reduce the HSP90 mRNA level. The animal experiments demonstrated the favorable curative effects of the TP and Curc-NPs, and the tumor inhibition rate reached 68.78%. The results of the pathological examinations demonstrated that the nanoparticles had no significant toxic effects on important organs. In conclusion, the TP and Curc-NPs exerted synergistic effects on ovarian cancer in vitro and in vivo, and the toxicity caused by triptolide may be reduced by curcumin through anti-oxidative stress effects. The TP and Curc-NPs could be a promising strategy for ovarian cancer.


Assuntos
Nanopartículas , Neoplasias Ovarianas , Animais , Apoptose , Fosfatos de Cálcio , Linhagem Celular Tumoral , Curcumina , Diterpenos , Compostos de Epóxi , Feminino , Fenantrenos , Éteres Fenílicos , Polietilenoglicóis
17.
J Biomed Nanotechnol ; 13(11): 1413-1424, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31271128

RESUMO

Triptolide (TP), a diterpenoid triepoxide purified from the Chinese traditional medicine Tripterygium wilfordii Hook F (TWHF), possesses potent anti-tumor activities against several malignancies, including ovarian cancer. However, its short half-life in circulation and severe reproductive toxicity prohibit the clinical use of TP. In this study, we engineered novel nanoparticles consisting of calcium phosphate conjugated TP-loaded liposomes (TP@Lips-Ca/P), constituted of mPEGDPPE2000, to improve the circulation time, stability and biodistribution of TP. The average particles size was 134.1 nm, and the drug loading efficiency and encapsulation efficiency were 1.31 ± 0.13% and 72.31 ± 3.11% respectively. TP@Lips-Ca/P exhibits greatly enhanced anti-tumor effects on SKOV-3 ovarian cancer cells compared to TP alone. We further demonstrated that apoptosis of SKOV-3 cells induced by TP@Lips-Ca/P resulted from excessive accumulation of reactive oxygen species (ROS). ROS activates the MAPK signal pathway, leading to induction of apoptosis and inhibition of tumor growth. In addition, we found that TP@Lips-Ca/P displays significantly reduced toxicity toward the female reproductive system compared to free TP. In conclusion, TP@Lips-Ca/P nanoparticles are a promising novel chemotherapy approach for ovarian cancer.

18.
Mol Cell Endocrinol ; 433: 26-34, 2016 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-27212205

RESUMO

In this investigation, a model of type 2 diabetes mellitus (T2DM) was used on Sprague-Dawley (SD) rats to clarify more details of the mechanism in the therapy of T2DM. D-chiro-inositol (DCI) was administrated to the diabetic rats as two doses [30, 60 mg/(kg·body weight·day)]. The biochemical indices revealed that DCI had a positive effect on hypoglycemic activity and promoted the glycogen synthesis. The rats in DCI high-dosage group had a blood glucose reduction rate of 21.5% after 5 weeks of treatment, and had insulin content in serum about 15.3 ± 2.37 mIU/L which was significantly decreased than diabetes control group. Real-time polymerase chain reaction (RT-PCR) results revealed that DCI gave a positive regulation on glycogen synthase (GS) and protein glucose transporter-4 (Glut4). Western blotting suggested that DCI could up-regulated the expression of the phosphatidylinositol-3-kinase (PI3K) p85, PI3Kp110, GS as well as the phosphorylation of protein kinase B (Akt) both in the liver and the skeletal muscle. The results also revealed that DCI enhanced the Glut4 expression on skeletal muscle. Above all, DCI played a positive role in regulating insulin-mediated glucose uptake through the PI3K/Akt signaling pathway in T2DM rats.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Inositol/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Insulina/metabolismo , Resistência à Insulina/fisiologia , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley
19.
Int J Mol Sci ; 13(7): 8308-8323, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22942704

RESUMO

Fruit wastes are one of the main sources of municipal waste. In order to explore the potential of fruit wastes as natural resources of bioactive compounds, the antioxidant potency and total phenolic contents (TPC) of lipophilic and hydrophilic components in wastes (peel and seed) of 50 fruits were systematically evaluated. The results showed that different fruit residues had diverse antioxidant potency and the variation was very large. Furthermore, the main bioactive compounds were identified and quantified, and catechin, cyanidin 3-glucoside, epicatechin, galangin, gallic acid, homogentisic acid, kaempferol, and chlorogenic acid were widely found in these residues. Especially, the values of ferric-reducing antioxidant power (FRAP), trolox equivalent antioxidant capacity (TEAC) and TPC in the residues were higher than in pulps. The results showed that fruit residues could be inexpensive and readily available resources of bioactive compounds for use in the food and pharmaceutical industries.


Assuntos
Antioxidantes/isolamento & purificação , Frutas/química , Extratos Vegetais/isolamento & purificação , Antioxidantes/química , Oxirredução , Extratos Vegetais/química , Polifenóis/química , Polifenóis/isolamento & purificação , Resíduos
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