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1.
Chemistry ; 26(1): 139-142, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31680317

RESUMO

Cyclic naphthalene diimides (cNDIs), with a ferrocene moiety (cFNDs) and different linker lengths between the ferrocene and cNDI moieties, were designed and synthesized as redox-active, tetraplex-DNA ligands. Intramolecular stacking was observed between ferrocene and the NDI planes, which could affect the binding properties for G-quadruplexes. Interestingly, the circular dichroism spectrum of one of these compounds clearly shows new Cotton effects around 320-380 and 240 nm, which can be considered a direct evidence of intramolecular stacking of ferrocene and the NDI. Regarding recognition of hybrid G-quadruplexes, the less rigid structures (longer linkers) show higher binding affinity (106 m-1 order of magnitude). All new compounds show higher selectivity for G4 during electrochemical detection than noncyclic FND derivatives, which further identifies the redox-active potentiality of the cFNDs. Two of the three compounds tested even show preferential inhibition of cell growth in cancer cells over normal cells in a low concentration range, highlighting the potential for bioapplications of these cFNDs.


Assuntos
Compostos Ferrosos/química , Quadruplex G , Imidas/química , Metalocenos/química , Naftalenos/química , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Células HeLa , Humanos , Imidas/farmacologia , Ligantes , Naftalenos/farmacologia , Oxirredução , Telômero/química
2.
Chemistry ; 26(2): 384-389, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31550056

RESUMO

Phosphatidylinositol (PI) is the biosynthetic precursor for seven phosphoinositides, important signaling lipids in cells. A membrane-permeant caged PI derivative featuring a photo-removable coumarinyl group masking the negative charge of the phosphate, as well as two enzymatically removable butyrate esters for increased lipophilicity and for preventing phosphate migration, were synthesized. Rapid cell entry and cellular labeling in fixed cells was demonstrated by a photo-cross-linkable diazirine followed by attachment of a fluorophore through click chemistry. Using this technique, we found that the multifunctional caged PI derivative resided predominantly at internal membranes but rapidly changed to the plasma membrane after uncaging. Accordingly, a preliminary proteomic analysis of the lipid-protein conjugates revealed that the two major PI transport proteins PITPα and ß were prime targets of the photo-cross-linked PI derivative.


Assuntos
Fosfatidilinositóis/química , Coloração e Rotulagem/métodos , Membrana Celular/metabolismo , Química Click , Células HeLa , Humanos , Microscopia de Fluorescência , Fosfatidilinositóis/síntese química , Fosfatidilinositóis/metabolismo
3.
Arch Virol ; 165(1): 105-114, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31741095

RESUMO

Piwi-interacting RNAs (piRNAs) play pivotal roles in spermatogenesis and are widely distributed among somatic tissues. However, little is known about piRNAs in HeLa cells infected with coxsackievirus B3 (CVB3). In this study, we systematically investigated changes in piRNA expression in HeLa cells infected with CVB3 using high-throughput sequencing technology. piRNA expression profiles in CVB3-infected HeLa cells were examined at 3, 6 and 9 h postinfection (pi). Of the 32,826 piRNAs that were annotated in the NCBI database, 151,571, 89,698 and 76,626 piRNAs were detected in CVB3-infected HeLa cells at 3, 6 and 9 h pi, respectively. Compared with normal cells, 211, 72 and 94 piRNAs were differentially expressed in CVB3-infected HeLa cells at 3, 6 and 9 h pi, respectively. Thirteen piRNAs, including four novel piRNAs, exhibited concurrent changes in CVB3-infected HeLa cells. The changes in the expression of these 13 piRNAs was confirmed in CVB3-infected HeLa cells and 293T cells by stem-loop RT-qPCR at 3, 6 and 9 h pi. The target genes of 13 piRNAs were predicted. The four novel piRNAs were associated with LTR/ERV, LINE/L1 and LTR/ERVK repetitive elements located on different chromosomes. These findings may promote a better understanding of the regulatory mechanism of pathophysiological changes induced by CVB3 infection.


Assuntos
Infecções por Coxsackievirus/genética , Enterovirus Humano B/patogenicidade , RNA Interferente Pequeno/genética , Regulação da Expressão Gênica , Células HEK293 , Células HeLa , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Análise de Sequência de RNA/métodos
4.
Cancer Sci ; 111(1): 239-252, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31729096

RESUMO

Hypoxia-inducible factor 1 (HIF-1) is a critical heterodimeric transcription factor for tumor malignancy. Recently, ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) has been reported to function as a deubiquitinating enzyme for the stabilization of its α subunit (HIF-1α). In the present study, we showed that UCHL1 inhibition can be an effective therapeutic strategy against HIF-1-dependent tumor malignancy. In 2D monolayer culture, a UCHL1 inhibitor suppressed HIF activity and decreased the transcription of HIF downstream genes by inhibiting the UCHL1-mediated accumulation of HIF-1α. Phenotypically, UCHL1 inhibition remarkably blocked cell migration. In 3D spheroid culture models, ectopic expression of UCHL1 significantly upregulated malignancy-related factors such as solidity, volume, as well as viable cell number in an HIF-1α-dependent manner. Conversely, inhibition of the UCHL1-HIF-1 pathway downregulated these malignancy-related factors and also abolished UCHL1-mediated cell proliferation and invasiveness. Finally, inhibition of UCHL1 promoted HIF-1α degradation and lowered the expression of HIF-1 target genes in the 3D model, as also observed in 2D monolayer culture. Our research indicates that the UCHL1-HIF-1 pathway plays a crucial role in tumor malignancy, making it a promising therapeutic target for cancer chemotherapy.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Esferoides Celulares/patologia , Ubiquitina Tiolesterase/genética , Ubiquitinas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo/genética , Regulação da Expressão Gênica/genética , Células HeLa , Humanos , Regulação para Cima/genética
5.
Biosci Biotechnol Biochem ; 84(1): 31-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31794330

RESUMO

4-(2-Hydroxyphenethyl)-2,6-dimethoxyphenol, a bibenzyl, was isolated from the leaves of Empetrum nigrum var. japonicum, collected from Mount Tateyama. Japanese rock ptarmigans frequently eat the leaves and fruits of this plant. The structure of the bibenzyl was confirmed by NMR spectroscopic analysis and fully characterized. A synthesis of this compound was accomplished by coupling 2-hydroxyphenylacetic acid with syringaldehyde, decarboxylation of the resultant isoaurones, and hydrogenation of the double bond in the corresponding stilbene. This compound displayed cytotoxic activity against human cancer cells (HCT116 and Hela cells) and leukemia cells (HL-60 cells). The present study suggests that this plant serves as a source of biologically active natural products. Also, our findings provide information on the secondary metabolites in the diet of Japanese rock ptarmigans.


Assuntos
Bibenzilas/síntese química , Bibenzilas/farmacologia , Ericaceae/química , Extratos Vegetais/síntese química , Extratos Vegetais/farmacologia , Bacillus subtilis/efeitos dos fármacos , Bibenzilas/química , Bibenzilas/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Células HCT116 , Células HL-60 , Células HeLa , Humanos , Japão , Espectroscopia de Ressonância Magnética , Conformação Molecular , Neoplasias/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Pirogalol/análogos & derivados , Pirogalol/química
6.
J Colloid Interface Sci ; 559: 313-323, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675662

RESUMO

Antibiotic resistance is a common phenomenon observed during treatment with antibacterials. Use of nanozymes, especially those with synergistic enzyme-like activities, as antibacterials could overcome this problem, but their synthesis is limited by their high cost and/or complex production process. Herein, vanadium oxide nanodots (VOxNDs) were prepared via a one-step bottom-up ethanol-thermal method using vanadium trichloride as the precursor. VOxNDs alone possess bienzyme mimics of peroxidase and oxidase. Accordingly, highly efficient antibacterials against drug-resistant bacteria can be obtained through synergistic catalysis; the oxidase-like activity decomposes O2 to generate superoxide anion radical (O2-) and hydroxyl radicals (OH), and the intrinsic peroxidase-like activity can further induce the production of OH from external H2O2. Consequently, H2O2 concentration could decrease up to four magnitude orders with VOxNDs to achieve an antibacterial efficacy similar to that of H2O2 alone. Wound healing in vivo further confirms the high antibacterial efficiency, good biocompatibility, and application potential of the synergistic antibacterial system due to the "nano" structure of VOxNDs. The method of synthesis of nanodot antibacterials described in this paper is inexpensive, and the results of this study reveal the multi-enzymatic synergism of nanozymes.


Assuntos
Antibacterianos/química , Nanopartículas Metálicas/química , Óxidos/química , Compostos de Vanádio/química , Cicatrização/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química , Materiais Biomiméticos/química , Catálise , Sobrevivência Celular/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Células HeLa , Células Endoteliais da Veia Umbilical Humana , Humanos , Peróxido de Hidrogênio/química , Radical Hidroxila/química , Peroxidases/metabolismo , Ratos Sprague-Dawley , Staphylococcus aureus/efeitos dos fármacos
7.
J Colloid Interface Sci ; 558: 137-144, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31586733

RESUMO

Platinum oxide (PtOx) nanoparticles (NPs) have been shown to possess anticancer activity by releasing ionic Pt species under biological conditions. However, the dissolution kinetics and the changes in the chemical state of Pt during PtOx dissolution have not yet been studied. To fill this gap, we prepared a composite (designated as PtOx@MMT-2) containing PtOx NPs on hollow mesoporous silica nanospheres and studied the dissolution of the material in different biorelevant media. We found that the release of Pt was retarded due to the adsorption of biomolecules on PtOx NPs during the degradation of host silica. The biomolecules adsorption also lowered the accessibility of PtOx NPs, resulting in the reduced catalase-like activity of the NPs. In line with the results, the cytotoxicity of PtOx@MMT-2, which was positively correlated to the amount of Pt uptake, was reduced by biomolecules adsorption. Our findings should be applicable to other metal (oxide) NPs under biological conditions and may provide implications for the design of nanomaterials for practical therapeutic applications.


Assuntos
Materiais Biocompatíveis/química , Nanopartículas/química , Óxidos/química , Platina/química , Dióxido de Silício/química , Adsorção , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células HeLa , Humanos , Nanopartículas/uso terapêutico , Solubilidade
9.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(10): 926-931, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31814569

RESUMO

Objective To investigate the effect of acetyl coenzyme A synthase 2 (ACSS2) on the migration and invasion induced by nutrient stress (NS) in cervical cancer cells. Methods Immunohistochemistry was used to detect the expression and distribution of ACSS2 protein in 20 pairs of cervical tumors and their adjacent normal tissues. Cervical cancer HeLa cells and the normal cervical epithelial HCvEpC cells were cultured, and serum content in culture medium was reduced from 100 to 10 mL/L as NS treatment. Western blot analysis was performed to detect the expression of ACSS2, GSK-3ß, p-GSK-3ß, ß-catenin, ß-actin, E-cadherin, vimentin. Small interfering RNA (siRNA) was used to down-regulate the expression of ACSS2. Cell migration was assessed by wound healing test, and cell invasion was tested by TranswellTM assay. Results The expression level of ACSS2 in 20 cervical tumors was significantly higher as compared with the adjacent normal tissues. The levels of ACSS2 in HeLa cells could be significantly up-regulated by NS, while no marked change was seen in HCvEpC cells. The treatment of NS promoted the epithelial mesenchymal transformation (EMT) of HeLa cells, which could be effectively reversed by siRNA-ACSS2. The scratch results showed that NS increased the healing rate of HeLa cells, which could be blocked by ACSS2 silencing. Coincidently, the number of invasive cells was elevated after NS treatment, which could be partly reversed by siRNA-ACSS2. The expression of ACSS2, p-GSK-3ß and nuclear ß-catenin was up-regulated in HeLa cells treated with NS for 48 hours, while siRNA-ACSS2 down-regulated their expression. Conclusion Silencing ACSS2 expression inhibits migration and invasion of cervical cancer cells induced by NS, which is related to down-regulated Wnt/ß-catenin signaling pathway activity.


Assuntos
Acetato-CoA Ligase/genética , Inativação Gênica , Neoplasias do Colo do Útero/patologia , Via de Sinalização Wnt , Movimento Celular , Proliferação de Células , Meios de Cultura , Transição Epitelial-Mesenquimal , Feminino , Técnicas de Silenciamento de Genes , Células HeLa , Humanos , Invasividade Neoplásica , Neoplasias do Colo do Útero/genética
10.
Cell Physiol Biochem ; 53(6): 948-960, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31820855

RESUMO

BACKGROUND/AIMS: HOTAIR is a long non-coding RNA that promotes the development of human cancer. TET1 enzyme is involved in DNA demethylation by oxidation of 5-methylcytocine and it is considered a tumor suppressor in some types of cancer. HOTAIR and TET1 are involved in modulation of the Wnt/ß-catenin signaling pathway, but their role in cervical cancer remains to be elucidated. The aim of this work was to analyze the effect of HOTAIR in TET1 expression, Wnt/ß-catenin signaling, and expression, methylation and hidroxymethylation of some negative regulators of this pathway in HeLa cells. METHODS: HOTAIR and TET expression were analyzed by RT-qPCR and western blot. The HOTAIR knockdown was done with DsiRNA and the activity of the Wnt/ß-catenin signaling pathway through luciferase assays and ß-catenin nuclear translocation. The mRNA levels of SNAIL, EDN3, CYCD1, SPRY2 (targets of Wnt/ß-catenin pathway) PCDH10, SOX17, AJAP1, and MAGI2 (negative regulators of Wnt/ß-catenin pathway) were evaluated by RT-qPCR. The DNA methylation and hidroxymethylation of negative regulators of the Wnt/ß-catenin pathway were evaluated by methylation-specific PCR and chemical modification, followed by digestion and quantitative PCR. RESULTS: HOTAIR knockdown in HeLa cells decreased the activity of Wnt/ß-catenin signaling pathway. It increased the mRNA levels of Wnt/ ß-catenin negative regulators through a decrease in their promoter's methylation pattern. TET1 enzyme was also down-regulated in HOTAIR knockdown cells. CONCLUSION: Our study suggests a mechanism in which HOTAIR promotes the over-activation of Wnt/ß-catenin signaling pathway by downregulation of PCDH10, SOX17, AJAP1 and MAGI2 and also TET.


Assuntos
RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Via de Sinalização Wnt , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Metilação de DNA , Guanilato Quinases/genética , Guanilato Quinases/metabolismo , Células HeLa , Humanos , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Fatores de Transcrição SOXF/genética , Fatores de Transcrição SOXF/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
11.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(11): 1280-1286, 2019 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-31852648

RESUMO

OBJECTIVE: To investigate the effect of Golgi phosphoprotein 3 (Golph3) on paclitaxel- induced apoptosis and autophagy in HeLa cells. METHODS: HeLa cells were transfected with a lentiviral vector expressing Golph3 or a small interfering RNA (siRNA) targeting Golph3 for up-regulation or down-regulation of Golph3 which was verified by Western blotting. The autophagic bodies in the cells were observed using transmission electron microscopy. The expression of autophagy markers p62 and LC3 were detected using Western blotting, and the cell apoptosis was examined by PI/Anexin V-FITC double staining and flow cytometry. The effects of blocking autophagy was evaluated by treatment of the cells with the autophagy inhibitor 3-MA. RESULTS: Transmission electron microscopy showed that the lentivirus-mediated overexpression of Golph3 significantly increased the number of autophagic bodies and interference of Golph3 expression significantly decreased autophagic bodies in HeLa cells. Western blotting showed that Golph3 overexpression caused an increased expression of LC3 and decreased the accumulation of p62 in the cells, and interference of Golph3 resulted in the reverse changes. The cell apoptosis induced by paclitaxel was significantly decreased in Golph3-overexpressing HeLa cells and increased in the cells with Golph3 knockdown (P>0.01). Treatment with 3-MA alone did not obviously affect HeLa cell apoptosis, but in cells with Golph3 knockdown, 3-MA significantly enhanced paclitaxel-induced apoptosis (P>0.01). CONCLUSIONS: Up-regulation of Golph3 promotes autophagy and inhibits paclitaxel-induced apoptosis, whereas suppression of Golph3 inhibits autophagy and enhances paclitaxel- induced apoptosis in HeLa cells.


Assuntos
Autofagia , Apoptose , Células HeLa , Humanos , Proteínas de Membrana , Paclitaxel , Fosfoproteínas
12.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(5): 609-614, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31699190

RESUMO

Objective To detect the methylation status of SALL3 gene promoter region in normal cervical tissues,cervical cancer tissues,and cervical cancer cell lines and thus explore the relationship between methylation status and the expression of SALL3 gene.Methods The DNA methylation statuses of SALL3 gene in normal cervical,cervical cancer tissues and cervical cancer cell lines were analyzed by methylation-specific PCR(MS-PCR).The expressions of SALL3 mRNA in cervical cancer cell lines,cervical cancer tissues,and normal cervical tissues were detected by RT-PCR.Results In cervical cancer and matched peri-carcinomatous samples,the methylation levels of SALL3 were up-regulated(CCa vs.CCap:P=0.046;CCa vs.NC P=0.039)and the protein expressions were down-regulated(CCa vs.CCap:P=0.012;CCa vs.NC P=0.000)when compared with normal cervix samples.The mRNA levels of SALL3 in HeLa and SiHa cells treated with 5-Azacytidine were elevated in a dose-dependent manner(HeLa:P=0.001;SiHa:P=0.002).The methylation level of SALL3 was higher in high risk human papillomavirus(HPV)-positive cervical samples than in HPV-negative cervical samples(P=0.014),which also resulted in a descending SALL3 expression in HPV-positive samples(P=0.021).Conclusions The hypermethylation of SALL3 in promoter regions inhibits the expression of SALL3 in cervical cancer tissue samples.Infection with high-risk HPV serotypes may increase the methylation of SALL3 promoter region,silence its expression,and thus promote the development of cervical cancer.


Assuntos
Metilação de DNA , Proteínas de Homeodomínio/genética , Regiões Promotoras Genéticas , Fatores de Transcrição/genética , Neoplasias do Colo do Útero/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Infecções por Papillomavirus/genética , RNA Mensageiro/genética
14.
J Environ Pathol Toxicol Oncol ; 38(2): 173-183, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679280

RESUMO

In the present study, we investigated the effects of conditioned media (CM) collected from the cancer cell lines (K562, MCF-7, and HeLa) on peripheral blood mononuclear cells (PBMCs) isolated from the healthy human blood. The soluble factors in the CM are probably responsible for the differential mRNA expressions of Foxp3, Helios, Neuropilin- 1 (NRP-1), and glycoprotein A repetitions predominant (GARP), along with IFN-γ and TGF-ß in PBMCs cultured with cancer cells CM. The PBMCs cultured with CM of K562 showed increased expression of Foxp3, Helios, NRP-1, GARP, IFN-γ, and TGF-ß compared to PBMCs cultured with CM of MCF-7 and HeLa cells. In addition, the intracellular staining on PBMCs cultured with CM from cell lines were also evaluated for CD4, CD25, Foxp3, Helios, and NRP-1 by multicolor flow cytometry. The expression of CD4+CD25+Foxp3+, CD4+Helios+Foxp3+ and CD+NRP-1+Foxp3+ showed retarded cell population compared to control PBMCs. Our data suggest that soluble factors in CM of cancer cells may trigger the immune response in PBMCs resulting in a systematic response. Further research could lead to the identification of specific soluble factors that are involved in trafficking of cells into the immune cascades, which could be a safe and promising strategy for targeting human cancers.


Assuntos
Expressão Gênica , Interferon gama/genética , Leucócitos Mononucleares/metabolismo , Fator de Crescimento Transformador beta/genética , Meios de Cultivo Condicionados , Células HeLa , Humanos , Interferon gama/metabolismo , Células K562 , Células MCF-7 , Fator de Crescimento Transformador beta/metabolismo
15.
BMC Bioinformatics ; 20(1): 564, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718539

RESUMO

BACKGROUND: Analysing large and high-dimensional biological data sets poses significant computational difficulties for bioinformaticians due to lack of accessible tools that scale to hundreds of millions of data points. RESULTS: We developed a novel machine learning command line tool called PyBDA for automated, distributed analysis of big biological data sets. By using Apache Spark in the backend, PyBDA scales to data sets beyond the size of current applications. It uses Snakemake in order to automatically schedule jobs to a high-performance computing cluster. We demonstrate the utility of the software by analyzing image-based RNA interference data of 150 million single cells. CONCLUSION: PyBDA allows automated, easy-to-use data analysis using common statistical methods and machine learning algorithms. It can be used with simple command line calls entirely making it accessible to a broad user base. PyBDA is available at https://pybda.rtfd.io.


Assuntos
Algoritmos , Biologia Computacional/métodos , Automação , Metodologias Computacionais , Células HeLa , Humanos , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina
16.
J Oral Sci ; 61(4): 512-515, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31708552

RESUMO

Sodium hypochlorite (NaOCl) is widely used as an antimicrobial irrigant; however, it has cytotoxic and neurotoxic effects. For these reasons, development of new, safe irrigants other than NaOCl is long overdue. In the present study, the antimicrobial and noxious effects of acid-electrolyzed functional water (FW) were evaluated and compared with those of NaOCl. Enterococcus faecalis, Streptococcus mutans, Porphyromonas gingivalis, or Candida albicans were mixed with each tested solution for 30 s. The mixtures were then plated on brain-heart infusion agar plates, after which colony numbers were counted. Serially diluted acid FW was used to determine the actual chloride concentration (ACC) required for a bactericidal effect. Noxious effects were evaluated by measuring lactate dehydrogenase released from HeLa cells. Acid FW and NaOCl had similar bactericidal effects against all bacterial species but not against C. albicans. An ACC of at least 10 ppm was required in order to ensure effective bacteriocidal activity and induce significant lactate dehydrogenase release. Acid FW-treated HeLa cells exhibited healthy growth, with slight retardation as compared with non-treated cells. Because of its efficient bactericidal, and less noxious, effects on human cells, acid FW may be a useful irrigant for effective root canal treatment.


Assuntos
Irrigantes do Canal Radicular , Água , Enterococcus faecalis , Células HeLa , Humanos , Hipoclorito de Sódio
18.
Org Biomol Chem ; 17(45): 9693-9697, 2019 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-31691700

RESUMO

A series of cyclic Arg-rich mitochondria-penetrating peptides were prepared with variation in the macrocycle size and the chirality of Arg residues. A cyclic heptapeptide was demonstrated to be an efficient mitochondria-specific delivery vector for delivering membrane impermeable peptides.


Assuntos
Membrana Celular/metabolismo , Peptídeos Penetradores de Células/metabolismo , Mitocôndrias/metabolismo , Membrana Celular/química , Sobrevivência Celular , Peptídeos Penetradores de Células/química , Ciclização , Células HeLa , Humanos , Mitocôndrias/química , Conformação Molecular
19.
Genes Dev ; 33(23-24): 1751-1774, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31753913

RESUMO

Bromodomain proteins (BRD) are key chromatin regulators of genome function and stability as well as therapeutic targets in cancer. Here, we systematically delineate the contribution of human BRD proteins for genome stability and DNA double-strand break (DSB) repair using several cell-based assays and proteomic interaction network analysis. Applying these approaches, we identify 24 of the 42 BRD proteins as promoters of DNA repair and/or genome integrity. We identified a BRD-reader function of PCAF that bound TIP60-mediated histone acetylations at DSBs to recruit a DUB complex to deubiquitylate histone H2BK120, to allowing direct acetylation by PCAF, and repair of DSBs by homologous recombination. We also discovered the bromo-and-extra-terminal (BET) BRD proteins, BRD2 and BRD4, as negative regulators of transcription-associated RNA-DNA hybrids (R-loops) as inhibition of BRD2 or BRD4 increased R-loop formation, which generated DSBs. These breaks were reliant on topoisomerase II, and BRD2 directly bound and activated topoisomerase I, a known restrainer of R-loops. Thus, comprehensive interactome and functional profiling of BRD proteins revealed new homologous recombination and genome stability pathways, providing a framework to understand genome maintenance by BRD proteins and the effects of their pharmacological inhibition.


Assuntos
Instabilidade Genômica , Reparo de DNA por Recombinação/genética , Fatores de Transcrição/genética , Acetilação , Linhagem Celular , Quebras de DNA de Cadeia Dupla , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Células HEK293 , Células HeLa , Humanos , Transativadores/metabolismo , Fatores de Transcrição/análise , Ubiquitinação , Fatores de Transcrição de p300-CBP/genética , Fatores de Transcrição de p300-CBP/metabolismo
20.
Chem Commun (Camb) ; 55(96): 14534-14537, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31740902

RESUMO

Fe-N/C single atom catalysts (SACs) exhibit peroxidase-like, oxidase-like, catalase-like, and glutathione peroxidase-like activity. Fe-N/C SACs are successfully applied to control the intracellular H2O2 level. This study not only explores the types of SACs mimicking enzymes but also provides opportunities for SACs in biomedical and other bioengineering applications.


Assuntos
Materiais Biomiméticos/química , Carbono/química , Ferro/química , Nitrogênio/química , Espécies Reativas de Oxigênio/química , Materiais Biomiméticos/metabolismo , Materiais Biomiméticos/farmacologia , Catalase/química , Catalase/metabolismo , Catálise , Sobrevivência Celular/efeitos dos fármacos , Glutationa Peroxidase/química , Glutationa Peroxidase/metabolismo , Células HeLa , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Oxirredução , Porfirinas/química , Espécies Reativas de Oxigênio/metabolismo
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