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1.
Genome Med ; 13(1): 146, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493320

RESUMO

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) present unique molecular signatures, but the tumorigenesis of EBVaGCs and the role EBV plays during this process remain poorly understood. METHODS: We applied whole-exome sequencing, EBV genome sequencing, and whole-genome bisulfite sequencing to multiple samples (n = 123) derived from the same patients (n = 25), which covered saliva samples and different histological stages from morphologically normal epithelial tissues to dysplasia and EBVaGCs. We compared the genomic landscape between EBVaGCs and their precursor lesions and traced the clonal evolution for each patient. We also analyzed genome sequences of EBV from samples of different histological types. Finally, the key molecular events promoting the tumor evolution were demonstrated by MTT, IC50, and colony formation assay in vitro experiments and in vivo xenograft experiments. RESULTS: Our analysis revealed increasing mutational burden and EBV load from normal tissues and low-grade dysplasia (LD) to high-grade dysplasia (HD) and EBVaGCs, and oncogenic amplifications occurred late in EBVaGCs. Interestingly, within each patient, EBVaGCs and HDs were monoclonal and harbored single-strain-originated EBV, but saliva or normal tissues/LDs had different EBV strains from that in EBVaGCs. Compared with precursor lesions, tumor cells showed incremental methylation in promotor regions, whereas EBV presented consistent hypermethylation. Dominant alterations targeting the PI3K-Akt and Wnt pathways were found in EBV-infected cells. The combinational inhibition of these two pathways in EBV-positive tumor cells confirmed their synergistic function. CONCLUSIONS: We portrayed the (epi) genomic evolution process of EBVaGCs, revealed the extensive genomic diversity of EBV between tumors and normal tissue sites, and demonstrated the synergistic activation of the PI3K and Wnt pathways in EBVaGCs, offering a new potential treatment strategy for this disease.

2.
Diabetes Res Clin Pract ; 180: 109040, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34500005

RESUMO

OBJECTIVES: To develop and validate a model for predicting the risk of early diabetic foot ulcer (DFU) based on systematic review and meta-analysis. METHODS: Data were analyzed from the risk factors of DFU with their corresponding risk ratio (RR) by meta-analysis. The DFU prediction model included statistically significant risk factors from the meta-analysis, all of which were scored by its weightings, and the prediction model was externally validated using a validation cohort from China. The occurrence of early DFU was defined as patients with type 2 diabetes who were free of DFU at baseline and diagnosed with DFU at follow-up. Evaluation of model performance was based on the area under the discrimination receiver operating characteristic curve (ROC), with optimal cutoff point determined by calculation of sensitivity and specificity. Kaplan-Meier curve were performed tocompare the cumulative risk of different groups. RESULTS: Our meta-analysis confirmed a cumulative incidence of approximately 6.0% in 46,521 patients with diabetes. The final risk prediction model included Sex, BMI, HbA1c, Smoker, DN, DR, DPN, Intermittent Claudication, Foot care, and their RRs were 1.87, 1.08, 1.21, 1.77, 2.97, 2.98, 2.76, 3.77, 0.38, respectively. The total score of all risk factors was 80 points according to their weightings. The prediction model showed good discrimination with AUC = 0.798 (95 %CI 0.738-0.858). At the optimal cut-off value of 46.5 points, the sensitivity, specificity and Youden index were 0.769, 0.798 and 0.567, respectively. The final model stratified the validation cohort into low, low-intermediate, high-intermediate and high-risk groups; Compared with low-risk group, the RR with 95 %CI of developing DFU in high-intermediate and high-risk group were 17.23 (5.12-58.02), p < 0.01 and 46.11 (5.16-91.74), p < 0.01, respectively. CONCLUSION: We have developed a simple tool to facilitates early identification of patients with diabetes at high risk of developing DFU based on scores. This simple tool may improve clinical decision-making and potentially guide early intervention.

3.
Anal Chem ; 93(33): 11634-11640, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34378382

RESUMO

Exploring the ratiometric fluorescence biosensing of DNA-templated biemissive silver nanoclusters (AgNCs) is significant in bioanalysis, yet the design of a stimuli-responsive DNA device is a challenge. Herein, using the anti-digoxin antibody (anti-Dig) with two identical binding sites as a model, a tweezer-like DNA architecture is assembled to populate fluorescent green- and red-AgNCs (g-AgNCs and r-AgNCs), aiming to produce a ratio signal via specific recognition of anti-Dig with two haptens (DigH). To this end, four DNA probes are programmed, including a reporter strand (RS) dually ended with a g-/r-AgNC template sequence, an enhancer strand (ES) tethering two same G-rich tails (G18), a capture strand (CS) labeled with DigH at two ends, and a help strand (HS). Initially, both g-AgNCs and r-AgNCs wrapped in the intact RS are nonfluorescent, whereas the base pairing between RS, ES, CS, and HS resulted in the construction of DNA mechanical tweezers with two symmetric arms hinged by a rigid "fulcrum", in which g-AgNCs are lighted up due to G18 proximity ("green-on"), and r-AgNCs away from G18 are still dark ("red-off"). When two DigHs in proximity recognize and bind anti-Dig, the conformation switch of these tweezers resultantly occurs, taking g-AgNCs away from G18 for "green-off" and bringing r-AgNCs close to G18 for "red-on". As such, the ratiometric fluorescence of r-AgNCs versus g-AgNCs is generated in response to anti-Dig, achieving reliable quantization with a limit of detection at the picomolar level. Based on the fast stimulated switch of unique DNA tweezers, our ratiometric strategy of dual-emitting AgNCs would provide a new avenue for a variety of bioassays.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Anticorpos , DNA , Fluorescência , Prata , Espectrometria de Fluorescência
4.
Cancer Manag Res ; 13: 5989-6004, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34377019

RESUMO

Background: Currently, there is still a lack of understanding about the mechanism and therapeutic targets of pancreatic adenocarcinoma (PAAD). The potential of miRNA-mRNA networks for the identification of regulatory mechanisms involved in PAAD development remains unexplored. Methods: We compared differentially expressed miRNAs (DEMIs) and differentially expressed genes (DEGs) in PAAD and normal tissues from the Gene Expression Omnibus (GEO) database. Transcription factors (TFs) were obtained from FunRich. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs and DEMIs were implemented using Database for Annotation, Visualization and Integrated Discovery (DAVID). Then, key miRNAs and targeted mRNAs were identified by assessment of their expression and prognosis in UALCAN and Kaplan-Meier plotters. In the last step, the candidate miRNA-mRNA selected was confirmed by real-time quantitative polymerase chain reaction (qRT-PCR). Results: We distinguished 62 significant DEMIs, 1314 upregulated DEGs, and 1110 downregulated DEGs. The top 10 TFs were identified. In total, there were 160 hub genes obtained by intersecting the set of 2224 predicted targets with the set of significant DEGs. And we selected 8 key miRNAs. Furthermore, low expression of miR-455-3p in PAAD tissue was closely connected with poor prognosis, and only 5 target mRNAs were predicted to be increased in PAAD tissue with poor prognosis. Therefore, a novel miRNA-hub gene regulatory network in PAAD was constructed. Finally, in vitro experiments indicated that miR-455-3p expression was decreased in PAAD sample. HOXC4, DLG4, DYNLL1 and FBXO45 were validated by qRT-PCR as highly probable targets of miR-455-3p. Conclusion: A novel miRNA-mRNA axis has been discovered that may be involved in the regulation of transcriptional disorders and affected the survival of PAAD patients, which would provide a novel strategy for the treatment of PAAD.

5.
J Immunother Cancer ; 9(7)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34253636

RESUMO

BACKGROUND: A major current challenge is to exploit tertiary lymphoid structures (TLSs) to promote the lymphocyte infiltration, activation and differentiation by tumor antigens to increase antitumor immune responses. The mechanisms that underlie the role of TLS formation in the adaptive immune responses against nasopharyngeal carcinoma (NPC) remain largely unknown. METHODS: Cell populations and the corresponding markers were identified by single-cell RNA sequencing and fluorescence-activated cell sorting analysis. In vitro differentiation experiments were used to simulate the generation, regulation and function of the Th-CXCL13 cell subset in the tumor microenvironment of NPC. These were followed by histological evaluation of the colocalization of tumor-associated B cells (TABs) and Th-CXCL13 cells within TLSs, and statistical analysis of the relationship between the cells in TLSs and overall survival. RESULTS: A PD-1+CXCR5-CD4+ Th-CXCL13 cell subset was identified in NPC. This subset was a major source of CXCL13, representing the majority of the CD4+ T cells at levels comparable with Th1 and Tfh cells present in the TLSs. Monocytes activated by toll-like receptor 4 agonists served as the antigen-presenting cells that most efficiently triggered the expansion of Th-CXCL13 cells. Transforming growth factor beta 1 (TGF-ß1) stimulation and activation of Sox4 were critical for the induction and polarization of Th-CXCL13 cells in this process. The potential functional contributions of TABs recruited by Th-CXCL13 cells which induced plasma cell differentiation and immunoglobulin production via interleukin-21 and CD84 interactions in the TLSs demonstrated improved survival. CONCLUSIONS: Induction of Th-CXCL13 cells links innate inflammation to immune privilege in tumor-associated TLSs and might predict better survival.

6.
Shanghai Kou Qiang Yi Xue ; 30(2): 124-128, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-34109348

RESUMO

PURPOSE: To investigate the clinical outcomes, including survival and periapical healing rates and failure causes, of root canal treatment for patients with periapical lesion. METHODS: A retrospective cohort study was conducted which enrolled patients admitted for the evaluation and management of periapical lesion with root canal treatment. The primary predictor variables were difficulty assessment of root canal therapy (DARCT),which was divided into lower(DARCT =3-4), medium (DARCT =5-7) and higher (DARCT =8-9) difficulty root canal, in terms of canal length, curvature and calcification. The primary outcome measurement was the incidence of periapical healing and survival rate. Potential confounders included patient demographics, canal number, root canal filling, and coronal restoration. SPSS 21.0 software package was used for data analysis. RESULTS: The 5-year survival rate was 81.4%(83/102) and healing rate was 77.1% (64/83). DARCT was significantly associated with the survival rate(P=0.017). Root fracture, deep pockets lesions and periodontal abscess were observed in DARCT with a value of 8-9(P=0.027), leading to tooth extraction. The teeth with multiple root canals were extracted due to recurrent or persistent periapical lesion (P=0.004). Chi-square test showed that root canal number (P=0.021), quality of root canal filling (P=0.006) as well as DARCT (P=0.000) were significantly correlated with the final healing rate. Multivariate logistic regression analysis showed that DARCT (P=0.000) and the quality of root canal filling (P=0.033) were associated with the final healing rate. CONCLUSIONS: DARCT and the quality of root canal filling play key roles in the clinical prognosis of periapical lesion, DARCT and number of root canal are more likely to be correlated with failure.


Assuntos
Periodontite Periapical , Materiais Restauradores do Canal Radicular , Cavidade Pulpar , Humanos , Periodontite Periapical/terapia , Estudos Retrospectivos , Obturação do Canal Radicular , Tratamento do Canal Radicular
7.
Bioorg Chem ; 110: 104802, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33730672

RESUMO

Ataxia telangiectasia and Rad3-related protein (ATR) plays a crucial role in cancer and has become a promising target for cancer therapy. Daphnegiravone D (DGD), which could induce apoptosis and oxidative stress in hepatocellular carcinoma (HCC) cells, but the detailed target protein was still unclear. The study provided that the possible target of DGD against HCC cells was determined by isobaric labels for relative and absolute quantification (iTRAQ) assay. In all changed proteins the fold change of ATR was particularly significant. The results from GO, KEGG and PPI analysis showed that DNA damage, cell cycle, apoptosis, DNA repair related pathways changed and ATR was exactly related to them. Moreover, the mRNA and protein of ATR were both decreased in a concentration-dependent manner, and the results of molecular docking also verified the binding. Additionally, cellular thermal shift assay (CETSA) suggested that DGD could directly target at ATR protein. Furthermore, the knockdown of ATR could increase apoptosis and reactive oxygen species (ROS) which induced by DGD. Since ATR inhibitors were generally used in combination with chemotherapy drugs (especially DNA damage drugs) in clinical trials, we investigated the combined application of DGD and oxaliplatin. The results showed that DGD combined with OXA also increased the apoptosis and ROS production of Hep3B cells over either drug alone. Taken together, this study revealed that DGD targeting ATR could be a promising therapeutic strategy for the treatment of liver cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Daphne/química , Flavonoides/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Flavonoides/química , Flavonoides/isolamento & purificação , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais Cultivadas
8.
Anal Chim Acta ; 1147: 155-164, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33485574

RESUMO

Effective enantioselective recognition with chiral nanomaterials remains a challenge in the field of chemistry and biology. In this paper, a pair of left- and right-handed polyaniline (defined as S-PANI and R-PANI) were synthesized by chemical oxidation of aniline to form a specially twisted nanoribbon, which was induced by enantiomeric camphorsulfonic acid. Both S-PANI and R-PANI were used to construct electrochemical chiral sensors for the discrimination of tryptophan isomers (D- and L-Trp). Owing to the formation of efficient chiral nanospace with special nanoribbon morphology and enormous amounts of oxygen-containing functional groups of S-PANI or R-PANI, the high enantioselectivity was obtained with the recognition efficiency of 4.90 (D-Trp) on S-PANI and 4.20 (L-Trp) on R-PANI, respectively. The obtained chiral electrodes were also used for the determination of the enantiomeric excess (ee) for Trp, and a good linear relationship between peak currents and ee% of Trp was obtained. Furthermore, the strategy we proposed has tremendous potential in enantiomer recognition field.

9.
ACS Appl Mater Interfaces ; 12(52): 58094-58104, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33334099

RESUMO

The cocrystallization method that combines various constituents into cocrystals yields the newly formed materials with significantly enhanced charge transport properties. However, this strategy has not been greatly utilized in all-conjugated block copolymers (BCPs). Herein, we scrutinize the relationship between cocrystals and charge mobilities in all-conjugated BCPs (i.e., poly(3-butylthiophene)-block-poly(3-hexylthiophene); denoted P3BT-b-P3HT) by tuning their molecular weights and thermal annealing process. All the rod-rod BCPs form cocrystals with high charge mobilities than P3BT and P3HT homopolymers and P3BT/P3HT blend, imparting the cocrystal-facilitated charge transport because of the synergy of two conjugated components. Upon 150 °C treatment, their crystallinities increase and their charge mobilities at 15k, 18k, and 28k increase slightly. In contrast, P3BT-b-P3HT-12k shows decreased charge mobilities. It is due to the preferential increase of crystal size and order through the π-π stacking direction in the former while through the alkyl stacking direction in the latter. Intriguingly, when these P3BT-b-P3HT cocrystals experience two-step thermal treatment, P3BT-b-P3HT-12k retains its cocrystalline structure, while microphase separation of P3BT and P3HT occurs in P3BT-b-P3HT-15k, 18k, and 28k with different degrees. All P3BT-b-P3HT BCPs exhibit decreased charge mobilities. This study demonstrates the cocrystallization-promoted charge mobility in all-conjugated BCPs, which may facilitate their application in a wide range of optoelectronic devices.

10.
J Clin Pathol ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004423

RESUMO

AIMS: Liver hepatocellular carcinoma (LIHC) is the main manifestation of primary liver cancer, with low survival rate and poor prognosis. Medical decision-making process of LIHC is so complex that new biomarkers for diagnosis and prognosis have yet to be explored, this study aimed to identify the genes involved in the pathophysiology of LIHC and biomarkers that can be used to predict the prognosis of LIHC. METHODS: Six Gene Expression Omnibus (GEO) datasets selected from GEO were screened and integrated to find out the differential expression genes (DEGs) obtained from LIHC and normal hepatic tissues. The Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analysis of DEGs was implemented by DAVID. The Protein-protein interaction network was performed via STRING. In addition, Cox regression model was used to construct a gene prognostic signature. RESULTS: We ascertained 10 hub genes, nine of them (CDK1, CDC20, CCNB1, Thymidylate synthetase, Nuclear division cycle80, NUF2, MAD2L1, CCNA2 and BIRC5) as biomarkers of progression in LIHC patients. We also build a six gene prognosis signature (SOCS2, GAS2L3, NLRP5, TAF3, UTP11 and GAGE2A), which can be implemented to predict over survival effectively. CONCLUSIONS: We revealed promising genes that may participate in the pathophysiology of LIHC, and found available biomarkers for LIHC prognosis prediction, which were significant for researchers to further understand the molecular basis of LIHC and direct the synthesis medicine of LIHC.

11.
Bioorg Chem ; 104: 104267, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32920350

RESUMO

Crataegus pinnatifida has been famous for its nutritional purpose. However, systematic investigation on the bioactive constituents is still lacking, although this fruit has been reported for its cytotoxic effect before. In this study, two pairs of new lignan enantiomers (1a/1b, 2a/2b), which isolated using chiral chromatographic column from the fruits of C. pinnatifida were studied. The absolute configurations of enantiomers were determined by comparison between the experimental electronic circular dichroism (ECD) and calculated ECD spectra. Among them, 1a/1b exhibited a better cytotoxic effect in hepatocellular carcinoma Hep3B cells with an IC50 value of 34.97 ± 2.74 and 17.42 ± 0.71 µM, respectively. In addition, 1b induced much more apoptotic, autophagic cells than 1a in Hep3B cells. Furthermore, the underlying mechanism was demonstrated that p38 activation could promote 1b-induced apoptosis and autophagy. Moreover, 1b-induced apoptosis was significantly decreased in the presence of autophagic inhibitor Bafilomycin A1 (Baf A1), suggesting that the induction of autophagy enhanced apoptotic cell death in 1b-treated cells. In general, these findings provide a valuable basis for further understanding the effect of 8-O-4' lignans in C. pinnatifida on cytotoxic effect.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Crataegus/química , Lignanas/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lignanas/química , Lignanas/isolamento & purificação , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
12.
Nanomaterials (Basel) ; 10(10)2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32993059

RESUMO

In our work, passively mode-locked and Q-switched Er-doped fiber lasers (EDFLs) based on titanium disulfide (TiS2) as a saturable absorber (SA) were generated successfully. Stable mode-locked pulses centred at 1531.69 nm with the minimum pulse width of 2.36 ps were obtained. By reducing the length of the laser cavity and optimizing the cavity loss, Q-switched operation with a maximum pulse energy of 67.2 nJ and a minimum pulse duration of 2.34 µs was also obtained. Its repetition rate monotonically increased from 13.17 kHz to 48.45 kHz with about a 35 kHz tuning range. Our experiment results fully indicate that TiS2 exhibits excellent nonlinear absorption performance and significant potential in acting as ultra-fast photonics devices.

13.
Cell Res ; 30(11): 950-965, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32901110

RESUMO

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy with a complex tumor ecosystem. How the interplay between tumor cells, EBV, and the microenvironment contributes to NPC progression and immune evasion remains unclear. Here we performed single-cell RNA sequencing on ~104,000 cells from 19 EBV+ NPCs and 7 nonmalignant nasopharyngeal biopsies, simultaneously profiling the transcriptomes of malignant cells, EBV, stromal and immune cells. Overall, we identified global upregulation of interferon responses in the multicellular ecosystem of NPC. Notably, an epithelial-immune dual feature of malignant cells was discovered and associated with poor prognosis. Functional experiments revealed that tumor cells with this dual feature exhibited a higher capacity for tumorigenesis. Further characterization of the cellular components of the tumor microenvironment (TME) and their interactions with tumor cells revealed that the dual feature of tumor cells was positively correlated with the expression of co-inhibitory receptors on CD8+ tumor-infiltrating T cells. In addition, tumor cells with the dual feature were found to repress IFN-γ production by T cells, demonstrating their capacity for immune suppression. Our results provide new insights into the multicellular ecosystem of NPC and offer important clinical implications.

14.
Oncol Lett ; 20(4): 60, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32793313

RESUMO

Pancreatic adenocarcinoma (PAAD) is a type of malignant tumor with the highest mortality rate among all neoplasms worldwide, and its exact pathogenesis is still poorly understood. Timely diagnosis and treatment are of great importance in order to decrease the mortality rate of PAAD. Therefore, identifying new biomarkers for diagnosis and prognosis is essential to enable early detection of PAAD and to improve the overall survival (OS) rate. In order to screen and integrate differentially expressed genes (DEGs) between PAAD and normal tissues, a total of seven datasets were downloaded from the Gene Expression Omnibus database and the 'limma' and 'robustrankggreg' packages in R software were used. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the DEGs was performed using the Database for Annotation, Visualization and Integrated Discovery website, and the protein-protein interaction network analysis was performed using the Search Tool for the Retrieval of Interacting Genes/Proteins database. A gene prognostic signature was constructed using the Cox regression model. A total of 10 genes (CDK1, CCNB1, CDC20, ASPM, UBE2C, TPX2, TOP2A, NUSAP1, KIF20A and DLGAP5) that may be associated with pancreatic adenocarcinoma were identified. According to the differentially expressed genes in The Cancer Genome Atlas, the present study set up four prognostic signatures (matrix metalloproteinase 12, sodium voltage-gated channel α subunit 11, tetraspanin 1 and SH3 domain and tetratricopeptide repeats-containing 2), which effectively predicted OS. The hub genes that were highly associated with the occurrence, development and prognosis of PAAD were identified, which may be helpful to further understand the molecular basis of pancreatic cancer and guide the synthesis of drugs for PPAD.

15.
Methods Enzymol ; 640: 63-82, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32560806

RESUMO

Engineered fluorescent proteins have been extensively used in biological research for the study of gene expression, protein function and trafficking, and protein-protein interactions. In addition, fluorescent proteins have also been engineered to act as biosensing agents to detect intracellular signaling molecules and other small-molecule metabolites. Although they have been engineered extensively to achieve novel properties, fluorescent proteins are traditionally modified using the 20 canonical amino acids. This limits the number of functional groups that are available to the design and construction of novel fluorescent proteins. The expansion of the genetic code through the incorporation of noncanonical amino acids presents an opportunity to add new functionalities with the intent of modifying chemical and physical properties of fluorescent proteins. Herein we provide a general procedure for the site-specific incorporation of noncanonical amino acids into fluorescent proteins in live cells. We will also discuss a noncanonical amino acid-containing fluorescent protein sensor that is based on a general protection-deprotection design strategy, for the selective detection and quantification of Hg2+.


Assuntos
Aminoácidos , Proteínas , Aminoácidos/genética , Corantes Fluorescentes , Código Genético , Proteínas/genética
16.
Sci Rep ; 10(1): 3167, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32081915

RESUMO

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affects the joints. Overweight and obesity can aggravate disease activity and clinical outcome in patients with RA. However, the role of bariatric surgery in inducing weight loss in the treatment of RA has not been confirmed. In this 12-month prospective cohort study, RA patients with obesity who were referred to our hospital were included. Thirty-two patients were classified into the bariatric surgery group according to the patient's decision after a comprehensive assessment of surgery indications, and 33 patients received only pharmacotherapy for RA. At the 12-month follow-up, the response rates of ACR20, ACR50 and ACR70 were 75.0% vs. 51.5%, 53.1% vs. 39.4% and 31.3% vs. 21.2% in the bariatric surgery and non-surgery groups, respectively (all p < 0.05); the mean DAS28-ESR, DAS28-CRP and cDAI scores were 1.5 ± 0.9 vs. 2.4 ± 1.4, 1.2 ± 0.9 vs. 2.2 ± 1.7 and 9.5 ± 6.8 vs. 15.8 ± 12.5, respectively, in surgical patients compared to non-surgical patients (all p < 0.05). Compared to baseline, after 12 months, a significant reduction was observed in the use of leflunomide, biological agents, combination treatments, and NSAIDs in both groups (p < 0.05 or p < 0.01). However, there was no difference in medication use between the 2 groups either at baseline or at the 12-month follow-up (all p > 0.05). Compared to non-surgical patients, in RA patients with obesity, weight loss after bariatric surgery was associated with lower disease activity. Medication tapering for RA in patients who underwent bariatric surgery was not superior to that in non-surgical patients.


Assuntos
Artrite Reumatoide/complicações , Artrite Reumatoide/cirurgia , Cirurgia Bariátrica , Obesidade/complicações , Obesidade/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Estômago/cirurgia , Resultado do Tratamento
17.
Int J Cancer ; 147(2): 505-518, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32064600

RESUMO

Although early detection and systemic therapies have improved the diagnosis and clinical cure rate of breast cancer, breast cancer remains the most frequently occurring malignant cancer in women due to a lack of sufficiently effective treatments. Thus, to develop potential targeted therapies and thus benefit more patients, it is helpful to understand how cancer cells work. ZIC family members have been shown to play important roles in neural development and carcinogenesis. In our study, we found that ZIC2 is downregulated in breast cancer tissues at both the mRNA and protein levels. Low expression of ZIC2 was correlated with poor outcome in breast cancer patients and serves as an independent prognostic marker. Furthermore, overexpression of ZIC2 repressed, whereas knockdown of ZIC2 promoted, cell proliferation and colony formation ability in vitro and tumor growth in vivo. Using ChIP-seq and RNA-seq analysis, we screened and identified STAT3 as a potential target for ZIC2. ZIC2 bound to the STAT3 promoter and repressed the promoter activities of STAT3. ZIC2 knockdown induced the expression of STAT3, increasing the level of phosphorylated STAT3. These results suggest that ZIC2 regulates the transcription of STAT3 by directly binding to the STAT3 promoter. Additionally, interfering STAT3 with siRNAs or inhibitors abrogated the oncogenic effects induced by decreased ZIC2. Taken together, our results indicate that ZIC2 serves as a useful prognostic marker in breast cancer and acts as a tumor suppressor by regulating STAT3, implying that STAT3 inhibitors might provide an alternative treatment option for breast cancer patients with ZIC2 downregulation.


Assuntos
Neoplasias da Mama/patologia , Regulação para Baixo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Sequenciamento de Cromatina por Imunoprecipitação , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Camundongos , Transplante de Neoplasias , Fosforilação , Prognóstico , Regiões Promotoras Genéticas , Análise de Sequência de RNA , Transdução de Sinais
18.
J Geriatr Cardiol ; 17(12): 740-749, 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33424941

RESUMO

Background: It is unclear whether catheter ablation (CA) for atrial fibrillation (AF) affects the long-term prognosis in the elderly. This study aims to evaluate the relationship between CA and long-term outcomes in elderly patients with AF. Methods: Patients more than 75 years old with non-valvular AF were prospectively enrolled between August 2011 and December 2017 in the Chinese Atrial Fibrillation Registry Study. Participants who underwent CA at baseline were propensity score matched (1:1) with those who did not receive CA. The outcome events included all-cause mortality, cardiovascular mortality, stroke/transient ischemic attack (TIA), and cardiovascular hospitalization. Results: Overall, this cohort included 571 ablated patients and 571 non-ablated patients with similar characteristics on 18 dimensions. During a mean follow-up of 39.75 ± 19.98 months (minimum six months), 24 patients died in the ablation group, compared with 60 deaths in the non-ablation group [hazard ratio (HR) = 0.49, 95% confidence interval (CI): 0.30-0.79, P = 0.0024]. Besides, 6 ablated and 29 non-ablated subjects died of cardiovascular disease (HR = 0.25, 95% CI: 0.11-0.61, P = 0.0022). A total of 27 ablated and 40 non-ablated patients suffered stroke/TIA (HR = 0.79, 95% CI: 0.48-1.28, P = 0.3431). In addition, 140 ablated and 194 non-ablated participants suffered cardiovascular hospitalization (HR = 0.84, 95% CI: 0.67-1.04, P = 0.1084). Subgroup analyses according to gender, type of AF, time since onset of AF, and anticoagulants exposure in initiation did not show significant heterogeneity. Conclusions: In elderly patients with AF, CA may be associated with a lower incidence of all-cause and cardiovascular mortality.

19.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4844-4851, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872591

RESUMO

In this work,a high performance liquid chromatography-ultraviolet( HPLC-UV) detection technology was used to establish fingerprint analysis method for Sanye Tangzhiqing Decoction following an analytical quality by design( AQb D) approach. Firstly,column temperature,flow rate,and gradient elution conditions were determined as the method parameters needing to be optimized. Then according to the results of definitive screening design,three critical method attributes( CMAs) were identified,including peak number,the percentage of common peak area to total peak area,and retention time of the last peak. A stepwise regression method was used then to build quantitative models between CMAs and method parameters. Probability-based design space was calculated and successfully verified using the experimental error simulation method. After the analysis conditions were optimized,the contents of six components,namely chlorogenic acid,paeoniflorin,rutin,hyperoside,quercetin-3-O-ß-D-glucuronide,and salvianolic acid B were simultaneously determined. There were 19 common peaks in the fingerprint and their common peak area accounted for 96% of the total peak area. Both fingerprint and quantitative analysis methods were validated applicable in methodology study,and they can be applied to determine new samples.


Assuntos
Medicamentos de Ervas Chinesas , Ácido Clorogênico , Cromatografia Líquida de Alta Pressão
20.
Nat Prod Res ; : 1-5, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31741408

RESUMO

Daphne giraldii Nitsche, belongs to Daphne genus, has been reported to exert anti-tumor activities. Our previous study suggested that flavones from Daphne giraldii have significant inhibitory effects on hepatocellular carcinoma (HCC) cells. However, the potential target of this type flavone was still unknown. In this study, 74 flavonoids compounds of Daphne giraldii and 41 potential targets of HCC were analyzed by the network, the most potential target was histone deacetylase 6 (HDAC6). Considering the cytotoxicity, compound 70 (Daphnegiravone D, DGD) was chosen for further confirmation. Molecular docking study revealed that DGD formed high binding affinity with HDAC6. Concomitantly, pharmacological studies indicated that DGD could inhibit the expression of HDAC6 in vitro and in vivo. In this study, network pharmacology along with experimental validation predicted and verified HDAC6 as one of potential targets of flavones, these investigations provide a new insight for further study of Daphne giraldii on HCC treatment.

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