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1.
BMC Cancer ; 22(1): 488, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505294

RESUMO

BACKGROUND: Emerging evidence has identified miR-138 as a tumor suppressor that can suppress the proliferation of various cancers. Meanwhile, the cause of abnormal miR-138 expression in cervical cancer remains uncertain. This study clarified the mechanism by which miR-138 regulates proliferation, invasion, metastasis, and EMT in cervical cancer cells. RESULTS: miR-138 expression in human cervical cancer and adjacent normal tissue was measured using qPCR. SiHa and C33A cells were used to determine the function of miR-138 via miR-138 mimic or inhibitor transfection, followed by wound healing, Cell Counting Kit-8, flow cytometry, and Transwell assays. Epithelial and mesenchymal marker expression was analyzed using Western blotting. DNA methylation in the miR-138 promoter was examined using bisulfite sequencing PCR. The downstream target genes of miR-138 were identified via bioinformatics analysis and luciferase reporter assays. A tumor xenograft model was employed to validate DNA methylation-induced miR-138 downregulation and tumor growth inhibition in cervical cancer in vivo. miR-138 levels were significantly lower in cervical cancer tissues than in adjacent control tissues. Furthermore, lower miR-138 expression and higher CpG methylation in the miR-138 promoter were identified in lymph node-positive metastatic cervical cancer tumors versus that in non-metastatic tumor tissues. Upon miR-138 overexpression, cell proliferation, metastasis, invasion, and EMT were suppressed. miR-138 agomir transfection and demethylating drug treatment significantly inhibited cervical tumor growth and EMT in tumor xenograft models. DNA methylation inhibited miR-138 transcription, and enhancer of zeste homolog 2 (EZH2) downregulation mediated the tumor suppressor function of miR-138 in cervical cancer. CONCLUSION: We demonstrated that miR-138 suppresses tumor progression by targeting EZH2 in cervical cancer and uncovered the role of DNA methylation in the miR-138 promoter in its downregulation. These findings demonstrated the potential of miR-138 to predict disease metastasis and/or function as a therapeutic target in cervical cancer.


Assuntos
MicroRNAs , Neoplasias do Colo do Útero , Linhagem Celular Tumoral , Proliferação de Células/genética , Metilação de DNA , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Feminino , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias do Colo do Útero/patologia
2.
Front Nutr ; 9: 885662, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571906

RESUMO

The effect of fermentation treatment on the surface morphology, crystal structure, molecular weight, chain length distribution, and physicochemical properties of corn starch was investigated using natural fermentation of corn ballast. The amylose content in corn ballast starch reduced at first after natural fermentation, then grew, following the same trend as solubility. There were certain erosion marks on the surfaces of fermented corn ballast starch granules. The crystalline structure of corn ballast starch remained the same, i.e., a typical A-type crystalline structure, at different fermentation times; however, the intensities of diffraction peaks were different. The weight-average molecular weight of starch first increased and then decreased after fermentation. The content of low-molecular-weight starch (peak 3) decreased from 25.59 to 24.7% and then increased to 25.76%, while the content of high-molecular-weight starch (peak 1) increased from 51.45 to 53.26%, and then decreased to 52.52%. The fermentation time showed a negative correlation with the viscosity of starch, and the pasting temperature first increased, and then decreased. Natural fermentation can be used as a technical means to produce corn starch products as a result of the experiments' findings, and future experiments will detect and analyze the bacterial structure of corn fermentation broth in order to better understand the molecular mechanism of natural fermentation affecting the structure and physicochemical properties of corn starch.

3.
Analyst ; 147(3): 542, 2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-34989362

RESUMO

Correction for 'High-resolution DNA size enrichment using a magnetic nano-platform and application in non-invasive prenatal testing' by Bo Zhang et al., Analyst, 2020, 145, 5733-5739, DOI: 10.1039/D0AN00813C.

4.
Sci Total Environ ; 804: 150218, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34798744

RESUMO

In this study, knowledge gaps on Sb concentration in rocks, ores, tailings, soil, river water, sediments, and crops of mine areas were identified and discussed in terms of contamination levels, spatial distribution, and environmental effects. Accordingly, Xunyang Hg-Sb mine, the largest Hg-Sb deposit in China as research region in this study, field sampling and laboratory analysis were conducted. The results showed elevated concentrations of Sb in the soil, sediment, and river water. The X-ray diffraction analysis indicated that the main minerals of the rocks were quartz, dolomite, calcite, and margarite. Based on the TESCAN integrated mineral analyzer analysis, the main ore minerals in the Gongguan mine were dolomite (93.97%), cinnabar (2.50%), stibnite (2.48%), calcite (0.38%), and quartz (0.38%). The µ-XRF analysis indicated that Sb distribution was similar to those of S and O, instead of those of Hg and As. The clear spatial variation of Sb concentration in environmental media, mines, tailings, and settling ponds affected Sb accumulation. Actinobacteriota, Proteobacteria, Acidobacteriota, and Chloroflexi were the dominant phyla in the soil. Patescibacteria, Proteobacteria, and Bdellovibrionota were negatively correlated with Sb in the soil (p < 0.05). Exposure to Sb through maize grain and cabbage consumption poses serious non-carcinogenic health risk for residents. This work provides a scientific basis for the environmental quality assessment of Sb mine areas and development of applicable guidelines.


Assuntos
Mercúrio , Poluentes do Solo , Antimônio/análise , China , Monitoramento Ambiental , Mercúrio/análise , Mineração , Solo , Poluentes do Solo/análise
5.
Acta Biochim Biophys Sin (Shanghai) ; 53(11): 1450-1458, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34596216

RESUMO

Atrial fibrosis is a crucial mechanism responsible for atrial fibrillation (AF). Sex-determining region Y-box containing gene 9 (Sox9) plays a pivotal role in fibrosis of many organs such as the skin, kidney, and liver. However, there are few studies about the occurrence and maintenance of Sox9 in atrial fibrosis. In this study, we investigated the role of Sox9 in the fibrotic phenotype of human atrial tissues and rat atrial fibroblasts in vitro. In the human right atrial tissue, Masson's trichrome staining, immunofluorescence, real-time quantitative polymerase chain reaction, and western blot analysis were carried out to explore the relationship between Sox9 and atrial fibrosis at the morphological, functional, and molecular levels. In cultured atrial fibroblasts, Sox9 was overexpressed by adenovirus or depleted by siRNA, and then, recombinant human transforming growth factor (TGF)-ß1 was added. Immunofluorescence analysis, western blot analysis, Transwell assay, and scratch assay were used to analyze the cells. In patient atrial tissues, Sox9 was increased with worsened atrial fibrosis, and this increase was related to AF severity. In rat atrial fibroblasts, Sox9 was promoted by TGF-ß1, and the α-smooth muscle actin (α-SMA) protein level and the ability of cell migration were increased after Sox9 overexpression by adenovirus, while the α-SMA protein level and the cell migration ability were decreased after Sox9 depletion by siRNA. In conclusion, Sox9 is involved in the regulation of fibrosis in the atria and may be located downstream of TGF-ß1. Our findings may provide a new perspective to treat atrial fibrosis during AF.


Assuntos
Fibrilação Atrial/genética , Fibroblastos/metabolismo , Cardiopatias Congênitas/genética , Cardiopatia Reumática/genética , Fatores de Transcrição SOX9/genética , Fator de Crescimento Transformador beta1/genética , Actinas/genética , Actinas/metabolismo , Adulto , Animais , Fibrilação Atrial/metabolismo , Fibrilação Atrial/patologia , Fibrilação Atrial/cirurgia , Movimento Celular , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Conexina 43/genética , Conexina 43/metabolismo , Feminino , Fibroblastos/patologia , Fibrose , Regulação da Expressão Gênica , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Átrios do Coração/cirurgia , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Cultura Primária de Células , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Cardiopatia Reumática/metabolismo , Cardiopatia Reumática/patologia , Cardiopatia Reumática/cirurgia , Fatores de Transcrição SOX9/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo
6.
Molecules ; 26(18)2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34576992

RESUMO

The extracellular polysaccharide (EPS) matrix embedding microbial cells and soil particles plays an important role in the development of biological soil crusts (BSCs), which is widely recognized as beneficial to soil fertility in dryland worldwide. This study examined the EPS-producing bacterial strains YL24-1 and YL24-3 isolated from sandy soil in the Mu Us Desert in Yulin, Shaanxi province, China. The strains YL24-1 and YL24-3 were able to efficiently produce EPS; the levels of EPS were determined to be 257.22 µg/mL and 83.41 µg/mL in cultures grown for 72 h and were identified as Sinorhizobium meliloti and Pedobacter sp., respectively. When the strain YL24-3 was compared to Pedobacter yulinensis YL28-9T using 16S rRNA gene sequencing, the resemblance was 98.6% and the strain was classified as Pedobacter sp. using physiological and biochemical analysis. Furthermore, strain YL24-3 was also identified as a subspecies of Pedobacter yulinensis YL28-9T on the basis of DNA-DNA hybridization and polar lipid analysis compared with YL28-9T. On the basis of the EPS-related genes of relevant strains in the GenBank, several EPS-related genes were cloned and sequenced in the strain YL24-1, including those potentially involved in EPS synthesis, assembly, transport, and secretion. Given the differences of the strains in EPS production, it is possible that the differences in gene sequences result in variations in the enzyme/protein activities for EPS biosynthesis, assembly, transport, and secretion. The results provide preliminary evidence of various contributions of bacterial strains to the formation of EPS matrix in the Mu Us Desert.


Assuntos
Matriz Extracelular de Substâncias Poliméricas/química , Pedobacter/isolamento & purificação , Pedobacter/fisiologia , Sinorhizobium meliloti/isolamento & purificação , Sinorhizobium meliloti/fisiologia , Técnicas de Tipagem Bacteriana , China , DNA Bacteriano/genética , Clima Desértico , Matriz Extracelular de Substâncias Poliméricas/genética , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Espaço Extracelular/química , Ácidos Graxos/análise , Metais Pesados/farmacologia , Hibridização de Ácido Nucleico , Pedobacter/citologia , Pedobacter/efeitos dos fármacos , Filogenia , RNA Ribossômico 16S/genética , Sinorhizobium meliloti/citologia , Sinorhizobium meliloti/efeitos dos fármacos , Microbiologia do Solo
7.
Front Nutr ; 8: 820715, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35118113

RESUMO

OBJECTIVES: The effects of high-temperature, high-pressure, and ultrasonic treatment on the physicochemical properties and structure of soluble dietary fibers in millet bran were studied to provide a comprehensive reference for the utilization of millet bran. METHODS: Different physical methods were used to treat millet bran dietary fibers, and their microstructures and Fourier-transform infrared spectra before and after modification were compared. The physicochemical properties (water-holding capacity, swelling capacity, oil-holding capacity, fat-binding capacity, cation exchange capacity), total antioxidant capacity, and thermal characteristics were also analyzed. RESULTS: There were no significant changes in the chemical groups of millet bran's soluble dietary fibers after modification, but cracks appeared on the surface of the fibers and the structure became loose and porous. Fiber agglomeration was observed, as well as improved thermal stability. After modification, the water-holding capacity, swelling capacity, oil-holding capacity, fat-binding capacity, and cation exchange capacity of millet bran were improved. When compared to the original soluble dietary fibers, ultrasound-treated fibers showed the most substantial improvement in all four capabilities, with increases of 140, 50, 78.1, 65.7, and 37.8%, respectively, compared with the original soluble dietary fibers (P < 0.05). The total antioxidant capacity of the ultrasound-treated fibers was found to be higher than those of the fibers that underwent the other three treatments (P < 0.05). CONCLUSIONS: The physicochemical qualities and structural characteristics of the soluble dietary fibers in millet bran are affected by all three physical modification methods; however, the physicochemical properties of the ultrasound-treated fibers are most significantly improved.

8.
J Am Chem Soc ; 142(42): 17928-17932, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33026224

RESUMO

Fractals are of fundamental importance in science and technology. Theoretical simulations indicate that Sierpinski triangles (STs) possess specific optical and electronic properties. To study their properties and uncover their potential applications, it is necessary to pack STs into large-scale two-dimensional crystalline structures. Here, a series of ordered structures consisting of ST units are successfully constructed on gold surfaces through coordination between 1,3-bis(4-pyridyl) benzene molecules and Fe atoms. Crystals of STs are characterized by scanning tunneling microscopy. K-map analysis explains the structural formation mechanism, which is further verified by density functional theory calculations. The molecular free diffusion and nice structure matching between STs and gold surfaces play important roles in the formation of crystals of STs.

9.
Am J Transl Res ; 12(8): 4422-4433, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32913516

RESUMO

The focal point of this research was the functional role of RP11-395G23.3 in endometrial cancer (EC). The expression of RP11-395G23.3, microRNA (miRNA)-205-5p, and their target proteins were detected by quantitative real-time polymerase chain reaction and western-blot analyses. Flow cytometry and proliferation, Transwell, and wound healing assays were used to detect the effects of RP11-395G23.3 and miRNA-205-5p on tumor cell migration and proliferation in vitro. RP11-395G23.3 expression was negatively related to miRNA-205-5p, but positively related to phosphatase and tensin homolog (PTEN) expression in human EC tissues. We discovered that low RP11-395G23.3 expression was significantly related to advanced histological grade and lymphovascular space invasion in EC patients. In addition, overexpression of RP11-395G23.3 significantly inhibited the proliferation, invasion, migration, and induced apoptosis of Ishikawa and HEC-1A cells in vitro. Our results also showed that RP11-395G23.3 could directly bind to miRNA-205-5p through its miRNA response elements and eliminate the inhibitory effect of targeting gene PTEN, thus leading to the signaling pathway of phosphatidylinositol-3-kinase/AKT inactivation. We demonstrated for the first time that RP11-395G23.3 may inhibit the development and pathogenesis of EC by acting as a sponge for miRNA-205-5p and increasing PTEN expression. RP11-395G23.3 may be a target for the diagnosis and treatment of EC.

10.
J Healthc Eng ; 2020: 8812678, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32952990

RESUMO

Purpose: To establish the correlation model between Traditional Chinese Medicine (TCM) constitution and physical examination indexes by backpropagation neural network (BPNN) technology. A new method for the identification of TCM constitution in clinics is proposed, which is trying to solve the problem like shortage of TCM doctor, complicated process, low efficiency, and unfavorable application in the current TCM constitution identification methods. Methods: The corresponding effective samples were formed by sorting out and classifying the original data which were collected from physical examination indexes and TCM constitution types of 950 physical examinees, who were examined at the affiliated hospital of Chengdu University of TCM. The BPNN algorithm was implemented using the C# programming language and Google's AI library. Then, the training group and the test (validation) group of the effective samples were, respectively, input into the algorithm, to complete the construction and validation of the target model. Results: For all the correlation models built in this paper, the accuracy of the training group and the test group of entire physical examination indexes-constitutional-type network model, respectively, was 88% and 53%, and the error was 0.001. For the other network models, the accuracy of the learning group and the test group and error, respectively, was as follows: liver function (31%, 42%, and 11.7), renal function (41%, 38%, and 6.7), blood routine (56%, 42%, and 2.4), and urine routine (60%, 40%, and 2.6). Conclusions: The more the physical examination indexes are used in training, the more accurate the network model is established to predict TCM constitution. The sample data used in this paper showed that there was a relatively strong correlation between TCM constitution and physical examination indexes. Construction of the correlation model between physical examination indexes and TCM constitution is a kind of study for the integration of Chinese and Western medicine, which provides a new approach for the identification of TCM constitution, and it may be expected to avoid the existing problem of TCM constitution identification at present.


Assuntos
Lipídeos/sangue , Medicina Tradicional Chinesa , Redes Neurais de Computação , Exame Físico , Algoritmos , Inteligência Artificial , Análise Química do Sangue , Sistemas Computacionais , Coleta de Dados , Humanos , Testes de Função Hepática , Modelos Estatísticos , Reconhecimento Automatizado de Padrão , Linguagens de Programação , Reprodutibilidade dos Testes , Software , Urinálise
11.
Analyst ; 145(17): 5733-5739, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32748914

RESUMO

Precise DNA sizing can boost sequencing efficiency, reduce cost, improve data quality, and even allow sequencing of low-input samples, while current pervasive DNA sizing approaches are incapable of differentiating DNA fragments under 200 bp with high resolution (<20 bp). In non-invasive prenatal testing (NIPT), the size distribution of cell-free fetal DNA in maternal plasma (main peak at 143 bp) is significantly different from that of maternal cell-free DNA (main peak at 166 bp). The current pervasive workflow of NIPT and DNA sizing is unable to take advantage of this 20 bp difference, resulting in sample rejection, test inaccuracy, and restricted clinical utility. Here we report a simple, automatable, high-resolution DNA size enrichment workflow, named MiniEnrich, on a magnetic nano-platform to exploit this 20 bp size difference and to enrich fetal DNA fragments from maternal blood. Two types of magnetic nanoparticles were developed, with one able to filter high-molecular-weight DNA with high resolution and the other able to recover the remaining DNA fragments under the size threshold of interest with >95% yield. Using this method, the average fetal fraction was increased from 13% to 20% after the enrichment, as measured by plasma DNA sequencing. This approach provides a new tool for high-resolution DNA size enrichment under 200 bp, which may improve NIPT accuracy by rescuing rejected non-reportable clinical samples, and enable NIPT earlier in pregnancy. It also has the potential to improve non-invasive screening for fetal monogenic disorders, differentiate tumor-related DNA in liquid biopsy and find more applications in autoimmune disease diagnosis.


Assuntos
Ácidos Nucleicos Livres , Diagnóstico Pré-Natal , DNA/genética , Feminino , Humanos , Fenômenos Magnéticos , Gravidez , Análise de Sequência de DNA
12.
Int J Oncol ; 57(1): 355-363, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32319598

RESUMO

The aim of the present study was to determine the competitive endogenous RNA (ceRNA) network associated with long­coding RNA (lncRNA) LA16c­313D11.11 in endometrial cancer (EC). Initially, the expression levels of LA16c­313D11.11 in 60 EC tissues, 20 atypical hyperplasia endometrium (EAH) tissues and 20 normal endometrium tissues was determined. MicroRNA (miRNA/miR)­205­5p mimics and LA16c­313D11.11 mimics were transfected into HEC­1A and Ishikawa cells. The expression levels of miR­205­5p, LA16c­313D11.11 and their target proteins were assessed using reverse transcription­quantitative PCR or western blot analysis. Flow cytometry, Cell Counting kit­8 assays, Transwell migration assays and wound healing assays were performed to assess the effects of LA16c­313D11.11 and miR­205­5p on the migration and proliferation of tumor cells in vitro. The expression levels of LA16c­313D11.11 and phosphatase and tensin homolog deleted on chromosome ten (PTEN) in human EAH and EC tissues were significantly decreased, whereas the expression levels of miR­205­5p in EAH and EC tissues were significantly increased, compared with the normal endometrium tissues. The expression of LA16c­313D11.11 in human EC tissues negatively correlated with the expression of miR­205­5p. Additionally, the overexpression of LA16c­313D11.11 significantly reduced the invasion, migration and viability of HEC­1A and Ishikawa cells in vitro. LA16c­313D11.11 was shown to regulate the expression of PTEN, and the invasion, migration and viability of HEC­1A and Ishikawa cells, through its microRNA response element to compete for microRNA­205­5p. LA16c­313D11.11 was also shown to modulate the PI3K/AKT signaling pathway. Therefore, LA16c­313D11.11 acts as an effective ceRNA associated with a microRNA­205­5p­PTEN axis. LA16c­313D11.11 may inhibit the development and progression of EC by acting as a sponge of miR­205­5p, thus indirectly increasing the expression of PTEN.


Assuntos
Carcinogênese/genética , Neoplasias do Endométrio/genética , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/genética , RNA Longo não Codificante/metabolismo , Adulto , Idoso , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Endométrio/patologia , Endométrio/cirurgia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Histerectomia , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/agonistas , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
13.
Bioinformatics ; 36(3): 928-929, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31393560

RESUMO

SUMMARY: The lollipop-diagram is one of the widely used graphical representations to visualize and explore translational effects of genetic mutations in cancer genomics. However, an easy-to-use lollipop-diagram tool with full functionality is still lacking. Here, we introduce g3viz, an R package that enables researchers to explore genetic mutation data using a lollipop-diagram in a web browser. With a few lines of R code, users can interactively visualize data details, annotate findings and export resultant diagrams in high-quality figures. Because of usefulness and usability, g3viz can be generally exploited by researchers with different levels of bioinformatics skills and programming experience. AVAILABILITY AND IMPLEMENTATION: The R package is freely available under the MIT license from CRAN (http://cran.r-project.org/web/packages/g3viz). The g3lollipop JavaScript package is freely available under MIT license at GitHub (https://github.com/g3viz/g3lollipop.js). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Genômica , Software , Mutação , Proteômica , Navegador
14.
Exp Ther Med ; 19(1): 630-638, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31853324

RESUMO

MicroRNA-138 (miR-138) acts as a key regulator in the modulation of carcinogenesis in numerous tumor types. Chemoresistance is common and relevant to the failure of multiple treatment strategies for cervical cancer. However, the biological role of miR-138 in the progression and chemosensitivity of cervical cancer is still unclear. The present study aimed to investigate the expression, function and mechanism of miR-138 in cervical cancer. An miR-138 mimic, inhibitor and negative control were transfected into SiHa and C33A cells. The expression of miR-138 and its target were assessed by reverse transcription-PCR, western blotting and immunohistochemistry. The functional significance of miR-138 in tumor progression and chemosensitivity to cisplatin in vitro was examined by Cell Counting Kit-8, flow cytometry, wound healing and Transwell assays. A tumor xenograft model was used to validate the effects in vivo. These results demonstrated that miR-138 was significantly downregulated in cervical cancer cells. Overexpression of miR-138 suppressed cervical cancer cell proliferation, invasion, increased apoptosis and enhanced chemotherapy sensitivity in vivo and in vitro. Furthermore, bioinformatics analysis and dual luciferase reporter assays demonstrated that H2AX served as a target for miR-138, and the rescue experiment revealed that H2AX was a functional target of miR-138. The protective effects of miR-138 overexpression were dependent on H2AX. This study provides evidence that miR-138/H2AX may be a novel therapeutic target in cervical cancer.

15.
Nat Commun ; 9(1): 562, 2018 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-29422620

RESUMO

Multidrug resistance is a major challenge to cancer chemotherapy. The multidrug resistance phenotype is associated with the overexpression of the adenosine triphosphate (ATP)-driven transmembrane efflux pumps in cancer cells. Here, we report a lipid membrane-coated silica-carbon (LSC) hybrid nanoparticle that targets mitochondria through pyruvate, to specifically produce reactive oxygen species (ROS) in mitochondria under near-infrared (NIR) laser irradiation. The ROS can oxidize the NADH into NAD+ to reduce the amount of ATP available for the efflux pumps. The treatment with LSC nanoparticles and NIR laser irradiation also reduces the expression and increases the intracellular distribution of the efflux pumps. Consequently, multidrug-resistant cancer cells lose their multidrug resistance capability for at least 5 days, creating a therapeutic window for chemotherapy. Our in vivo data show that the drug-laden LSC nanoparticles in combination with NIR laser treatment can effectively inhibit the growth of multidrug-resistant tumors with no evident systemic toxicity.


Assuntos
Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Trifosfato de Adenosina/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Humanos , Células MCF-7 , Mitocôndrias/efeitos dos fármacos , NAD/metabolismo , Nanopartículas/química , Oxirredução , Dióxido de Silício/química
16.
Zhongguo Zhong Yao Za Zhi ; 42(9): 1747-1751, 2017 May.
Artigo em Chinês | MEDLINE | ID: mdl-29082700

RESUMO

Inflammation is one of the important risk factors of rheumatic diseases. Aconiti Radix is widely used for the treatment of rheumatism, which has significant anti-inflammatory effects. However, its anti-inflammatory mechanism on molecular level is still not clear. The purpose of this study is to illuminate the anti-inflammatory mechanism of Aconiti Radix based on the protein interaction network (PIN) analysis on molecular network level. The main anti-inflammatory components (aconitine, hypaconitine and mesaconitine) were chosen in this study to obtain the targets of the components and protein-protein information though databases retrieval and construct the PIN of Aconiti Radix. By a graph theoretic clustering algorithm molecular complex detection(MCODE), 13 modules were identified and analyzed by gene ontology(GO) enrichment. The results showed that the anti-inflammatory mechanism of Aconiti Radix was mainly associated with prostanoid metabolic process and leukocyte chemotaxis mediated by chemokines. In this study, the anti-inflammatory mechanism of Aconiti Radix was elucidated systematically from molecular network level, which provided the scientific basis for the treatment of rheumatic diseases.


Assuntos
Aconitum/química , Anti-Inflamatórios/química , Medicamentos de Ervas Chinesas/química , Mapas de Interação de Proteínas , Humanos , Plantas Medicinais/química
17.
ACS Cent Sci ; 3(8): 875-885, 2017 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-28852702

RESUMO

Stem cell therapy holds great potential for treating ischemic diseases. However, contemporary methods for local stem cell delivery suffer from poor cell survival/retention after injection. We developed a unique multiscale delivery system by encapsulating therapeutic agent-laden nanoparticles in alginate hydrogel microcapsules and further coentrapping the nano-in-micro capsules with stem cells in collagen hydrogel. The multiscale system exhibits significantly higher mechanical strength and stability than pure collagen hydrogel. Moreover, unlike nanoparticles, the nano-in-micro capsules do not move with surrounding body fluid and are not taken up by the cells. This allows a sustained and localized release of extracellular epidermal growth factor (EGF), a substance that could significantly enhance the proliferation of mesenchymal stem cells while maintaining their multilineage differentiation potential via binding with its receptors on the stem cell surface. As a result, the multiscale system significantly improves the stem cell survival at 8 days after implantation to ∼70% from ∼4-7% for the conventional system with nanoparticle-encapsulated EGF or free EGF in collagen hydrogel. After injecting into the ischemic limbs of mice, stem cells in the multiscale system facilitate tissue regeneration to effectively restore ∼100% blood perfusion in 4 weeks without evident side effects.

18.
ACS Nano ; 11(7): 6691-6702, 2017 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-28614653

RESUMO

Development of high-fidelity three-dimensional (3D) models to recapitulate the tumor microenvironment is essential for studying tumor biology and discovering anticancer drugs. Here we report a method to engineer the 3D microenvironment of human tumors, by encapsulating cancer cells in the core of microcapsules with a hydrogel shell for miniaturized 3D culture to obtain avascular microtumors first. The microtumors are then used as the building blocks for assembling with endothelial cells and other stromal cells to create macroscale 3D vascularized tumor. Cells in the engineered 3D microenvironment can yield significantly larger tumors in vivo than 2D-cultured cancer cells. Furthermore, the 3D vascularized tumors are 4.7 and 139.5 times more resistant to doxorubicin hydrochloride (a commonly used chemotherapy drug) than avascular microtumors and 2D-cultured cancer cells, respectively. Moreover, this high drug resistance of the 3D vascularized tumors can be overcome by using nanoparticle-mediated drug delivery. The high-fidelity 3D tumor model may be valuable for studying the effect of microenvironment on tumor progression, invasion, and metastasis and for developing effective therapeutic strategy to fight against cancer.


Assuntos
Técnicas de Cultura de Células/métodos , Descoberta de Drogas/métodos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Dispositivos Lab-On-A-Chip , Neoplasias/irrigação sanguínea , Animais , Antineoplásicos/farmacologia , Técnicas de Cultura de Células/instrumentação , Descoberta de Drogas/instrumentação , Ensaios de Seleção de Medicamentos Antitumorais/instrumentação , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Células MCF-7 , Camundongos Nus , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos
19.
Nat Commun ; 7: 13306, 2016 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-27786170

RESUMO

It is difficult to achieve minimally invasive injectable cell delivery while maintaining high cell retention and animal survival for in vivo stem cell therapy of myocardial infarction. Here we show that pluripotent stem cell aggregates pre-differentiated into the early cardiac lineage and encapsulated in a biocompatible and biodegradable micromatrix, are suitable for injectable delivery. This method significantly improves the survival of the injected cells by more than six-fold compared with the conventional practice of injecting single cells, and effectively prevents teratoma formation. Moreover, this method significantly enhances cardiac function and survival of animals after myocardial infarction, as a result of a localized immunosuppression effect of the micromatrix and the in situ cardiac regeneration by the injected cells.


Assuntos
Bioengenharia/métodos , Células-Tronco Embrionárias Murinas/citologia , Infarto do Miocárdio/terapia , Células-Tronco Pluripotentes/citologia , Transplante de Células-Tronco/métodos , Animais , Cápsulas , Agregação Celular/genética , Diferenciação Celular/genética , Células Cultivadas , Perfilação da Expressão Gênica/métodos , Injeções , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células-Tronco Embrionárias Murinas/metabolismo , Células-Tronco Pluripotentes/metabolismo
20.
Anal Chem ; 88(16): 8264-71, 2016 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-27409352

RESUMO

Dielectrophoresis (DEP) has been widely explored to separate cells for various applications. However, existing DEP devices are limited by the high cost associated with the use of noble metal electrodes, the need of high-voltage electric field, and/or discontinuous separation (particularly for devices without metal electrodes). We developed a DEP device with liquid electrodes, which can be used to continuously separate different types of cells or particles based on positive DEP. The device is made of polydimethylsiloxane (PDMS), and ionic liquid is used to form the liquid electrodes, which has the advantages of low cost and easy fabrication. Moreover, the conductivity gradient is utilized to achieve the DEP-based on-chip cell separation. The device was used to separate polystyrene microbeads and PC-3 human prostate cancer cells with 94.7 and 1.2% of the cells and microbeads being deflected, respectively. This device is also capable of separating live and dead PC-3 cancer cells with 89.8 and 13.2% of the live and dead cells being deflected, respectively. Moreover, MDA-MB-231 human breast cancer cells could be separated from human adipose-derived stem cells (ADSCs) using this device with high purity (81.8 and 82.5% for the ADSCs and MDA-MB-231 cells, respectively). Our data suggest the great potential of cell separation based on conductivity-induced DEP using affordable microfluidic devices with easy operation.


Assuntos
Separação Celular/métodos , Líquidos Iônicos/química , Linhagem Celular , Dimetilpolisiloxanos/química , Condutividade Elétrica , Eletrodos , Eletroforese , Humanos , Dispositivos Lab-On-A-Chip
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