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1.
Bioorg Med Chem Lett ; : 128410, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34626784

RESUMO

Four series of cajanonic acid A (CAA) derivatives have been designed and synthesized. The newly prepared compounds have been screened for glucose consumption activity in HepG2 cell lines and PPARγ antagonistic activity in HEK293 cell lines. Compound 26g bearing a tetrahydroisoquinolinone scaffold showed the most potent PPARγ antagonistic and hypoglycemic activities. An oral glucose tolerance test (OGTT) was performed and the results further confirmed that 26g was a potent hypoglycemic agent. In addition, the possible binding modes for compound 26g in the PPARγ protein have been investigated in this study.

2.
IEEE Trans Cybern ; PP2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34506295

RESUMO

Human parsing is a fine-grained semantic segmentation task, which needs to understand human semantic parts. Most existing methods model human parsing as a general semantic segmentation, which ignores the inherent relationship among hierarchical human parts. In this work, we propose a pose-guided hierarchical semantic decomposition and composition framework for human parsing. Specifically, our method includes a semantic maintained decomposition and composition (SMDC) module and a pose distillation (PC) module. SMDC progressively disassembles the human body to focus on the more concise regions of interest in the decomposition stage and then gradually assembles human parts under the guidance of pose information in the composition stage. Notably, SMDC maintains the atomic semantic labels during both stages to avoid the error propagation issue of the hierarchical structure. To further take advantage of the relationship of human parts, we introduce pose information as explicit guidance for the composition. However, the discrete structure prediction in pose estimation is against the requirement of the continuous region in human parsing. To this end, we design a PC module to broadcast the maximum responses of pose estimation to form the continuous structure in the way of knowledge distillation. The experimental results on the look-into-person (LIP) and PASCAL-Person-Part datasets demonstrate the superiority of our method compared with the state-of-the-art methods, that is, 55.21% mean Intersection of Union (mIoU) on LIP and 69.88% mIoU on PASCAL-Person-Part.

3.
Sheng Wu Gong Cheng Xue Bao ; 37(8): 2836-2844, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34472301

RESUMO

It has been reported that ODB genes play an important role in homologous recombination-directed DNA repair, suggesting their potential applications in plant breeding. To analyze the expression characteristics of tobacco NtODB gene, the cDNA sequence of NtODB was obtained using in silico cloning technique. The physicochemical properties, signal peptide, and advanced structures of the predicted protein were analyzed using bioinformatics tools. The results showed that the NtODB gene has a 579-bp open reading frame which encodes a protein with 192 amino acid residues. The protein NtODB is predicted to be alkaline and hydrophilic. Real-time quantitative PCR showed that NtODB was constitutively expressed in different tissues. Subcellular localization showed that NtODB was mainly expressed in cell membrane and chloroplast. These results may help us to better understand and elucidate the roles of ODB genes in the homologous recombination-directed DNA repair.


Assuntos
Biologia Computacional , Tabaco , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Simulação por Computador , DNA Complementar , Filogenia , Melhoramento Vegetal , Tabaco/genética
4.
Commun Biol ; 4(1): 1019, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465850

RESUMO

Despite the uniform mortality in pancreatic adenocarcinoma (PDAC), clinical disease heterogeneity exists with limited genomic differences. A highly aggressive tumor subtype termed 'basal-like' was identified to show worse outcomes and higher inflammatory responses. Here, we focus on the microbial effect in PDAC progression and present a comprehensive analysis of the tumor microbiome in different PDAC subtypes with resectable tumors using metagenomic sequencing. We found distinctive microbial communities in basal-like tumors and identified an increasing abundance of Acinetobacter, Pseudomonas and Sphingopyxis to be highly associated with carcinogenesis. Functional characterization of microbial genes suggested the potential to induce pathogen-related inflammation. Host-microbiota interplay analysis provided new insights into the tumorigenic role of specific microbiome compositions and demonstrated the influence of host genetics in shaping the tumor microbiome. Taken together, these findings indicated that the tumor microbiome is closely related to PDAC oncogenesis and the induction of inflammation. Additionally, our data revealed the microbial basis of PDAC heterogeneity and proved the predictive value of the microbiome, which will contribute to the intervention and treatment of disease.

5.
Clin Transl Med ; 11(9): e520, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34586739

RESUMO

BACKGROUND: The differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) is clinically challenging due to a lack of minimally invasive diagnosis methods. MicroRNAs (miRNAs) derived from small extracellular vesicles (EVs) in the blood have been reported as a promising diagnosis biomarker for various types of cancer. However, blood small EV miRNA signatures and their diagnostic value to differentiate between PDAC and CP remain to be determined. METHODS: In this study, 107 patients with PDAC or CP were recruited, and 90 patients were finally enrolled for a training cohort (n = 48) and test cohort (n = 42). Small RNA sequencing was used to assess the expression of blood small EV miRNAs in these patients. RESULTS: The linear model from the differentially expressed blood small EV miR-95-3p divided by miR-26b-5p showed an average sensitivity of 84.1% and an average specificity of 96.6% to identify PDAC from CP in the training cohort and the test cohort, respectively. When the model was combined with serum carbohydrate antigen 19-9 (CA19-9), the average sensitivity increased to 96.5%, and the average specificity remained at 96.4% of both cohorts, which demonstrated the best performance of all the published biomarkers for distinguishing between PDAC and CP. The causal analysis performed using the Bayesian network demonstrated that miR-95-3p was associated with a "consequence" of "cancer" and miR-26b-5p as a "cause" of "pancreatitis." A subgroup analysis revealed that blood small EV miR-335-5p/miR-340-5p could predict metastases in both cohorts and was associated with an overall survival (p = 0.020). CONCLUSIONS: This study indicated that blood small EV miR-95-3p/miR-26b-5p and its combination with serum levels of CA19-9 could separate PDAC from CP, and miR-335-5p/miR-340-5p was identified to associate with PDAC metastasis and poor prognosis. These results suggested the potentiality of blood small EV miRNAs as differential diagnosis and metastases biomarkers of PDAC.

6.
Curr Drug Deliv ; 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34420504

RESUMO

BACKGROUND: Hydrophilic hydroxypropyl methylcellulose (HPMC) matrix tablets are the standard role model of the oral controlled-release formulation. Nevertheless, the HPMC kinetics for the mechanistic understanding of drug release and hydrodynamic behaviors are rarely investigated. This study aims to investigate the release behaviors of both HPMC and paracetamol (model drug) from the hydrophilic matrix tablet. METHODS: Two different viscosity grades of HPMC were used (Low viscosity: 6 cps, High viscosity: 4,000 cps). Three different ratios of drug/HPMC (H:38.08%, M:22.85%, and L:15.23% (w/w) of HPMC amounts in total weight) matrix tablets were prepared by wet granulation technique. The release profiles of the drug and HPMC in a matrix tablet were quantitatively analyzed by HPLC and 1H-nuclear magnetic resonance (NMR) spectroscopy. The hydrodynamic changes of HPMC were determined by the gravimetric behaviors such as swelling and erosion rates, gel layer thickness, front movement data,and distributive near-infrared (NIR) chemical imaging of HPMC in a matrix tablet during the dissolution process. RESULTS: High viscosity HPMC tablets showed slower release of HPMC than the release rate of drug, suggesting that drug release preceded polymer release.Different hydration phenomenon was qualitatively identified and corresponded to the release profiles. The release behaviors of HPMC and drug in the tablet could be distinguished with the significant difference with fitted dissolution kinetics model (Low viscosity HPMC 6cps; Korsmeyer-Peppas model, High viscosity HPMC 4000cps; Hopfenberg model, Paracetamol; Weibull model) according to the weight of ingredients and types of HPMC. CONCLUSION: The determination of HPMC polymer release correlating with drug release, hydrodynamic behavior, and NIR chemical imaging of HPMC can provide new insights into the drug release-modulating mechanism in the hydrophilic matrix system.

7.
Carbohydr Polym ; 272: 118453, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34420713

RESUMO

The purpose of this study was to design alginate in situ forming gel (ISFG) injectable with clinically acceptable gelation time and controlled release of hydrophobic drug. Milled or unmilled paliperidone palmitate (PPP) was used. The gelation time was controlled by varying the ratios of glucono-d-lactone (GDL) and pyridoxal 5'-phosphate (PLP) in prefilled alginate solution mixtures (ASMs) containing PPP, CaCO3, GDL and PLP for clinically acceptable injectability. However, the gelation time was varied by the alginate type (M/G ratio), storage condition, and drug solubilizers. This ISFG exhibited 32.15 kPa of the maximal compressive stress without causing pain and stiffness. The ISFG containing conically milled PPP released PPP in a controlled manner without exhibiting any initial burst release for 4 weeks. The current alginate ISFG injectable using new combination of PLP and GDL could be used to deliver long-acting injectable drugs.

8.
Small ; : e2102155, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34309180

RESUMO

Energy shortages and greenhouse effects are two unavoidable problems that need to be solved. Photocatalytically converting CO2 into a series of valuable chemicals is considered to be an effective means of solving the above dilemmas. Among these photocatalysts, the utilization of black phosphorus for CO2 photocatalytic reduction deserves a lightspot not only for its excellent catalytic activity through different reaction routes, but also on account of the great preponderance of this relatively cheap catalyst. Herein, this review offers a summary of the recent advances in synthesis, structure, properties, and application for CO2 photocatalytic reduction. In detail, the review starts from the basic principle of CO2 photocatalytic reduction. In the following section, the synthesis, structure, and properties, as well as CO2 photocatalytic reduction process of black phosphorus-based photocatalyst are discussed. In addition, some possible influencing factors and reaction mechanism are also summarized. Finally, a summary and the possible future perspectives of black phosphorus-based photocatalyst for CO2 reduction are established.

9.
Cancer Lett ; 518: 207-213, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34271105

RESUMO

AJCC TNM stage and WHO grade (G) are two widely used staging systems to guide clinical management for pancreatic neuroendocrine neoplasms (panNENs), based on clinical staging and pathological grading information, respectively. We proposed to integrate TNM stage and G grade into one staging system (TNMG) and to evaluate its clinical application as a prognostic indicator for panNENs. Accordingly, 5254 patients diagnosed with panNENs were used to evaluate and to validate the applicability of TNMG to panNENs. The predictive accuracy of TNMG system was compared with that of each separate staging/grading system. We found that TNM stage and G grade were independent risk factors for survival in both the Surveillance, Epidemiology, and End Result (SEER) and multicenter series. The interaction effect between TNM stage and G grade was significant. Twelve subgroups combining the TNM stage and G grade were proposed in the TNMG stage, which were classified into five stages TNMG. According to the TNMG staging classification in the SEER series, the estimated median survival for stages I, II, III, IV, and V were 203, 174, 112, 61, and 8 months, respectively. The predictive accuracy of TNMG stage was higher than that of TNM stage and G grade used independently. The TNMG stage classification was more accurate in predicting panNEN patient's prognosis than either the TNM stage or G grade.

10.
Lancet Oncol ; 22(8): 1093-1102, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34237249

RESUMO

BACKGROUND: There is paucity of investigations into immunotherapy or targeted therapy for postoperative locally recurrent pancreatic cancer. We aimed to assess the efficacy of stereotactic body radiotherapy (SBRT) plus pembrolizumab and trametinib in these patients. METHODS: In this open-label, randomised, controlled, phase 2 study, participants were recruited from Changhai Hospital affiliated to Naval Medical University, Shanghai, China. Eligible patients were aged 18 years or older with histologically confirmed pancreatic ductal adenocarcinoma characterised by mutant KRAS and positive immunohistochemical staining of PD-L1, Eastern Cooperative Oncology Group performance status of 0 or 1, and documented local recurrence after surgery followed by chemotherapy (mFOLFIRINOX or 5-fluorouracil). Eligible participants were randomly assigned (1:1) using an interactive voice or web response system, without stratification, to receive SBRT with doses ranging from 35-40 Gy in five fractions, intravenous pembrolizumab 200 mg once every 3 weeks, and oral trametinib 2 mg once daily or SBRT (same regimen) and intravenous gemcitabine (1000 mg/m2) on day 1 and 8 of a 21-day cycle for eight cycles until disease progression, death, unacceptable toxicity, or consent withdrawal. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the as-treated population in all participants who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02704156, and is now complete. FINDINGS: Between Oct 10, 2016, and Oct 28, 2017, 198 patients were screen, of whom 170 patients were enrolled and randomly assigned to receive SBRT plus pembrolizumab and trametinib (n=85) or SBRT plus gemcitabine (n=85). As of the clinical cutoff date (Nov 30, 2020), median follow-up was 23·3 months (IQR 20·5-27·4). Median overall survival was 24·9 months (23·3-26·5) with SBRT plus pembrolizumab and trametinib and 22·4 months (95% CI 21·2-23·6) with SBRT plus gemcitabine (hazard ratio [HR] 0·60 [95% CI 0·44-0·82]; p=0·0012). The most common grade 3 or 4 adverse effects were increased alanine aminotransferase or aspartate aminotransferase (ten [12%] of 85 in SBRT plus pembrolizumab and trametinib group vs six [7%] of 85 in SBRT plus gemcitabine group), increased blood bilirubin (four [5%] vs none), neutropenia (one [1%] vs nine [11%]), and thrombocytopenia (one [1%] vs four [5%]). Serious adverse events were reported by 19 (22%) participants in the SBRT plus pembrolizumab and trametinib group and 12 (14%) in the SBRT plus gemcitabine group. No treatment-related deaths occurred. INTERPRETATION: The combination of SBRT plus pembrolizumab and trametinib could be a novel treatment option for patients with locally recurrent pancreatic cancer after surgery. Phase 3 trials are needed to confirm our findings. FUNDING: Shanghai Shenkang Center and Changhai Hospital. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Ductal Pancreático/terapia , Terapia Combinada/métodos , Neoplasias Pancreáticas/terapia , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Idoso , China , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiocirurgia/métodos
11.
Am J Med Sci ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34274323

RESUMO

BACKGROUND: Recent guidelines and randomized clinical trials favor the multivessel percutaneous coronary intervention (MV-PCI) strategy undertaken immediately or staged after primary PCI in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. However, the optimal strategy of MV-PCI remains unknown. METHODS: We conducted a search of PUBMED, EMBASE, Web of Science, the Cochrane database (CENTRAL), clinicaltrial.gov, and Google Scholar for studies comparing immediate versus staged MV-PCI in patients with STEMI and multivessel disease. Pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated using random-effects models. RESULTS: Eighteen (4 randomized clinical trials) studies with 8,100 patients fulfilled the inclusion criteria. Relative to staged MV-PCI, immediate MV-PCI was associated with higher short-term (within 30 days) (OR, 3.96; 95% CI, 2.07-7.59; P<0.0001) and long-term (above 6 months) mortality (OR, 2.12; 95% CI, 1.46-3.07; P<0.0001), short-term major adverse cardiovascular events (MACE)(OR, 1.99; 95% CI, 1.13-3.50; P=0.02) and cardiac death (OR, 4.78; 95% CI, 2.17-10.53; P=0.0001). There was a nonsignificant trend towards higher long-term MACE (OR, 1.23; 95% CI, 0.98-1.54; P=0.07) and cardiac death (OR, 1.75; 95% CI, 0.93-3.30; P=0.08) with immediate versus staged MV-PCI. Revascularization, myocardial infarction, and safety endpoints including stroke, major bleeding, and renal failure were similar between immediate versus staged MV-PCI. However, pooled analysis of randomized clinical trials did not show any significant differences in long-term MACE, all-cause mortality, myocardial infarction, and revascularization. CONCLUSIONS: Our meta-analysis suggests that among patients with STEMI and multivessel disease, staged instead of immediate MV-PCI may be the optimal revascularization strategy.

12.
Med Image Anal ; 73: 102150, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34303891

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and carries a dismal prognosis of ∼10% in five year survival rate. Surgery remains the best option of a potential cure for patients who are evaluated to be eligible for initial resection of PDAC. However, outcomes vary significantly even among the resected patients who were the same cancer stage and received similar treatments. Accurate quantitative preoperative prediction of primary resectable PDACs for personalized cancer treatment is thus highly desired. Nevertheless, there are a very few automated methods yet to fully exploit the contrast-enhanced computed tomography (CE-CT) imaging for PDAC prognosis assessment. CE-CT plays a critical role in PDAC staging and resectability evaluation. In this work, we propose a novel deep neural network model for the survival prediction of primary resectable PDAC patients, named as 3D Contrast-Enhanced Convolutional Long Short-Term Memory network (CE-ConvLSTM), which can derive the tumor attenuation signatures or patterns from patient CE-CT imaging studies. Tumor-vascular relationships, which might indicate the resection margin status, have also been proven to hold strong relationships with the overall survival of PDAC patients. To capture such relationships, we propose a self-learning approach for automated pancreas and peripancreatic anatomy segmentation without requiring any annotations on our PDAC datasets. We then employ a multi-task convolutional neural network (CNN) to accomplish both tasks of survival outcome and margin prediction where the network benefits from learning the resection margin related image features to improve the survival prediction. Our presented framework can improve overall survival prediction performances compared with existing state-of-the-art survival analysis approaches. The new staging biomarker integrating both the proposed risk signature and margin prediction has evidently added values to be combined with the current clinical staging system.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/cirurgia , Humanos , Margens de Excisão , Pâncreas , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Prognóstico , Tomografia Computadorizada por Raios X
13.
Compr Rev Food Sci Food Saf ; 20(4): 3579-3619, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34146455

RESUMO

Grape phenolic compounds undergo various types of transformations during winemaking under the influences of yeasts, which further impacts the sensory attributes, thus the quality of wine. Understanding the roles of yeasts in phenolics transformation is important for controlling wine quality through fermentation culture selection. This literature review discusses the mechanisms of how yeasts alter the phenolic compounds during winemaking, summarizes the effects of Saccharomyces cerevisiae and non-Saccharomyces yeasts on the content and composition of phenolics in wine, and highlights the influences of mixed cultural fermentation on the phenolic profile of wine. Collectively, this paper aims to provide a deeper understanding on yeast-phenolics interactions and to identify the current literature gaps for future research.

14.
J BUON ; 26(2): 643, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34077027

RESUMO

The Editors of JBUON issue an Expression of Concern to 'Tormentic acid induces anticancer effects in cisplatin-resistant human cervical cancer cells mediated via cell cycle arrest, ROS production, and targeting mTOR/PI3K/AKT signalling pathway', by Jinrong Wu, Ning Wang, Gang Jin, Lili Xue, JBUON 2020;25(1):74-79; PMID: 32277616. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

15.
J Hazard Mater ; 419: 126484, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34186427

RESUMO

An aromatic heterocyclic compound, 2-aminobenzothiazole (ABT), was used to decorate graphene oxide (GO) by a facile hydrothermal self-assembly procedure. The developed three-dimensional (3D) GO-ABT composite aerogels could be utilized as high-powered and sustainable adsorbents for the enrichment and recovery of low concentration rare earth elements (REEs) from aqueous solutions. The composition and microstructure of GO-ABT composites were explored various characterization methods. The enrichment properties of GO-ABT composites for REEs were investigated in detail, revealing the existence of S-, N- and -NH2 in ABT, as well as the carboxyl and hydroxyl groups of GO which might act as the major REE binding sites. The adsorption of GO-ABT composites for low concentration REEs could reach equilibrium in 30 min. Our investigations confirmed that the optimal pH value of GO-ABT composites for REEs was pH 4.0-5.0. For the adsorbent regeneration study, 50.0 mg of GO-ABT15:1/120 °C/6 h composite was used toward 20.0 mL of Er3+ solutions. After ten regeneration cycles, the adsorption rates of GO-ABT composites for Er3+ remained around 100%, and the desorption rates maintained over 90%. The long-term storage of the adsorbent did not affect its adsorption ability, while desorption rates increased, indicating it possessed relatively higher stability.

16.
Aging (Albany NY) ; 13(13): 17155-17176, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34081626

RESUMO

Hypoxia contributes significantly to the development of chemoresistance of many malignancies including esophageal cancer (EC). Accumulating studies have indicated that long non-coding RNAs play important roles in chemotherapy resistance. Here, we identified a novel lncRNA-EMS/miR-758-3p/WTAP axis that was involved in hypoxia-mediated chemoresistance to cisplatin in human EC. Hypoxia induced the expressions of lncRNA EMS and WTAP, and reduced the expression of miR-758-3p in EC cell line ECA-109. In addition, the expressions of EMS and WTAP were required for the hypoxia-induced drug resistance to cisplatin in EC cells, while overexpression of miR-758-3p reversed such chemoresistance. The targeting relationships between EMS and miR-758-3p, as well as miR-758-3p and WTAP, were verified by luciferase-based reporter assays and multiple quantitative assays after gene overexpression/knockdown. Moreover, we found significant correlations between tumor expressions of these molecules. Notably, higher levels of EMS/WTAP, or lower levels of miR-758-3p in tumors predicted worse survivals of EC patients. Furthermore, in a xenograft mouse model, targeted knockdown of EMS and WTAP in ECA-109 cells markedly attenuated the resistance of tumors to cisplatin treatments. Our study uncovers a critical lncRNA-EMS/miR-758-3p/WTAP axis in regulating hypoxia-mediated drug resistance to cisplatin in EC.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Ciclo Celular/genética , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Hipóxia/complicações , MicroRNAs/genética , Fatores de Processamento de RNA/genética , RNA Longo não Codificante/genética , Animais , Biomarcadores Tumorais , Linhagem Celular Tumoral , Neoplasias Esofágicas/mortalidade , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Nus , Valor Preditivo dos Testes , Análise de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Cell Death Dis ; 12(7): 628, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145224

RESUMO

With an increasing aging society, China is the world's fastest growing markets for oral implants. Compared with traditional oral implants, immediate implants cause marginal bone resorption and increase the failure rate of osseointegration, but the mechanism is still unknown. Therefore, it is important to further study mechanisms of tension stimulus on osteoblasts and osteoclasts at the early stage of osseointegration to promote rapid osseointegration around oral implants. The results showed that exosomes containing circ_0008542 from MC3T3-E1 cells with prolonged tensile stimulation promoted osteoclast differentiation and bone resorption. Circ_0008542 upregulated Tnfrsf11a (RANK) gene expression by acting as a miR-185-5p sponge. Meanwhile, the circ_0008542 1916-1992 bp segment exhibited increased m6A methylation levels. Inhibiting the RNA methyltransferase METTL3 or overexpressing the RNA demethylase ALKBH5 reversed osteoclast differentiation and bone resorption induced by circ_0008542. Injection of circ_0008542 + ALKBH5 into the tail vein of mice reversed the same effects in vivo. Site-directed mutagenesis study demonstrated that 1956 bp on circ_0008542 is the m6A functional site with the abovementioned biological functions. In conclusion, the RNA methylase METTL3 acts on the m6A functional site of 1956 bp in circ_0008542, promoting competitive binding of miRNA-185-5p by circ_0008542, and leading to an increase in the target gene RANK and the initiation of osteoclast bone absorption. In contrast, the RNA demethylase ALKBH5 inhibits the binding of circ_0008542 with miRNA-185-5p to correct the bone resorption process. The potential value of this study provides methods to enhance the resistance of immediate implants through use of exosomes releasing ALKBH5.


Assuntos
Reabsorção Óssea/metabolismo , Comunicação Celular , Diferenciação Celular , Exossomos/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese , RNA Circular/metabolismo , Células 3T3 , Homólogo AlkB 5 da RNA Desmetilase/genética , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Animais , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , Microambiente Celular , Exossomos/transplante , Feminino , Mecanotransdução Celular , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , MicroRNAs/metabolismo , Osseointegração , Osteoblastos/transplante , Osteoclastos/patologia , Células RAW 264.7 , RNA Circular/genética , Ratos , Receptor Ativador de Fator Nuclear kappa-B/genética , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Estresse Mecânico
18.
Sensors (Basel) ; 21(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067559

RESUMO

Weakly supervised instance segmentation (WSIS) provides a promising way to address instance segmentation in the absence of sufficient labeled data for training. Previous attempts on WSIS usually follow a proposal-based paradigm, critical to which is the proposal scoring strategy. These works mostly rely on certain heuristic strategies for proposal scoring, which largely hampers the sustainable advances concerning WSIS. Towards this end, this paper introduces a novel framework for weakly supervised instance segmentation, called Weakly Supervised R-CNN (WS-RCNN). The basic idea is to deploy a deep network to learn to score proposals, under the special setting of weak supervision. To tackle the key issue of acquiring proposal-level pseudo labels for model training, we propose a so-called Attention-Guided Pseudo Labeling (AGPL) strategy, which leverages the local maximal (peaks) in image-level attention maps and the spatial relationship among peaks and proposals to infer pseudo labels. We also suggest a novel training loss, called Entropic OpenSet Loss, to handle background proposals more effectively so as to further improve the robustness. Comprehensive experiments on two standard benchmarking datasets demonstrate that the proposed WS-RCNN can outperform the state-of-the-art by a large margin, with an improvement of 11.6% on PASCAL VOC 2012 and 10.7% on MS COCO 2014 in terms of mAP50, which indicates that learning-based proposal scoring and the proposed WS-RCNN framework might be a promising way towards WSIS.

19.
Biosensors (Basel) ; 11(5)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065240

RESUMO

Exosomes are a kind of membrane-bound phospholipid nanovesicle that are secreted extensively in a variety of biological fluids. Accumulating evidence has indicated that exosomes not only communicate with cells, but also perform functional roles in physiology and pathology. In addition, exosomes have also elicited a great deal of excitement due to their potential as disease biomarkers. Therefore, requirements for sensitive methods capable of precisely and specifically determining exosomes were needed. Herein, we not only develop a sensing surface to capture exosomes but also compare two surface proteins on exosomes, which are appropriate for detecting exosome surface markers by total internal reflected imaging ellipsometry (TIRIE). Protein G and antibody were immobilized on a thin layer of golden substrate to form the biosensing surface. The bio-interaction between antibodies and exosomes was recorded by the TIRIE in real time. The distance between exosomes adhered on a surface was 44 nm ± 0.5 nm. The KD  of anti-CD9 and exosome was lower than anti-CD63 and exosome by introducing pseudo-first-order interaction kinetics, which suggested that CD9 is more suitable for exosome surface markers than CD63. The limit of detection (LOD) of TIRIE was 0.4 µg/mL. In conclusion, we have proposed a surface for the detection of exosomes based on TIRIE, which can make the detection of exosomes convenient and efficient.


Assuntos
Biomarcadores , Técnicas Biossensoriais , Exossomos/química , Linhagem Celular Tumoral , Espectroscopia Dielétrica , Humanos , Limite de Detecção , Proteínas de Membrana , Ligação Proteica
20.
J Mater Chem B ; 9(20): 4241-4248, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34008693

RESUMO

A multifunctional nanoplatform (1), MnCO@TPP@C-TiO2, which consists of a carrier of carbon-doped TiO2 nanoparticles with surface covalent functionalization of manganese carbonyls and a directing group of triphenylphosphine, was prepared for mitochondria-targeted carbon monoxide (CO) delivery combined with photodynamic therapy (PDT). MnCO@TPP@C-TiO2 selectively localized in the mitochondria of HeLa cells where the overexpressed-H2O2 triggered CO release resulting in mitochondrial damage. And singlet oxygen species generated upon 808 nm near infrared light irradiation further destroyed the mitochondria and induced cancer cells apoptosis. Cytotoxicity assays revealed that the nanoplatform with mitochondria-targeted CO delivery and PDT exhibited the highest lethality against cancer cells in comparison with all the other control samples tested, and it showed good dark biocompatibility with normal cells that express low H2O2 levels. This work may provide new insights into combining CO-based gas therapy with traditional PDT for efficient cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Monóxido de Carbono/química , Complexos de Coordenação/farmacologia , Sistemas de Liberação de Medicamentos , Mitocôndrias/efeitos dos fármacos , Fotoquimioterapia , Oxigênio Singlete/química , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Raios Infravermelhos , Mitocôndrias/metabolismo , Estrutura Molecular , Tamanho da Partícula , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície , Células Tumorais Cultivadas
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