Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 268
Filtrar
1.
Radiology ; : 210407, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34981975

RESUMO

Background Improving diagnosis of ductal carcinoma in situ (DCIS) before surgery is important in choosing optimal patient management strategies. However, patients may harbor occult invasive disease not detected until definitive surgery. Purpose To assess the performance and clinical utility of mammographic radiomic features in the prediction of occult invasive cancer among women diagnosed with DCIS on the basis of core biopsy findings. Materials and Methods In this Health Insurance Portability and Accountability Act-compliant retrospective study, digital magnification mammographic images were collected from women who underwent breast core-needle biopsy for calcifications that was performed at a single institution between September 2008 and April 2017 and yielded a diagnosis of DCIS. The database query was directed at asymptomatic women with calcifications without a mass, architectural distortion, asymmetric density, or palpable disease. Logistic regression with regularization was used. Differences across training and internal test set by upstaging rate, age, lesion size, and estrogen and progesterone receptor status were assessed by using the Kruskal-Wallis or χ2 test. Results The study consisted of 700 women with DCIS (age range, 40-89 years; mean age, 59 years ± 10 [standard deviation]), including 114 with lesions (16.3%) upstaged to invasive cancer at subsequent surgery. The sample was split randomly into 400 women for the training set and 300 for the testing set (mean ages: training set, 59 years ± 10; test set, 59 years ± 10; P = .85). A total of 109 radiomic and four clinical features were extracted. The best model on the test set by using all radiomic and clinical features helped predict upstaging with an area under the receiver operating characteristic curve of 0.71 (95% CI: 0.62, 0.79). For a fixed high sensitivity (90%), the model yielded a specificity of 22%, a negative predictive value of 92%, and an odds ratio of 2.4 (95% CI: 1.8, 3.2). High specificity (90%) corresponded to a sensitivity of 37%, positive predictive value of 41%, and odds ratio of 5.0 (95% CI: 2.8, 9.0). Conclusion Machine learning models that use radiomic features applied to mammographic calcifications may help predict upstaging of ductal carcinoma in situ, which can refine clinical decision making and treatment planning. © RSNA, 2022.

2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(1): 21-25, 2022 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-34964960

RESUMO

OBJECTIVE: To identify the pathogenic variant for a husband with osteogenesis imperfecta and provide preimplantation genetic testing (PGT) for the couple. METHODS: High-throughput sequencing and Sanger sequencing were carried out to identify the pathologic variant in the husband patients. PGT of embryos was performed through direct detection of the mutation site. Meanwhile, chromosome aneuploidy of the blastocysts was screened. Following transplantation, cytogenetic and genetic testing of fetal amniotic fluid sample was carried out during mid-pregnancy. Chromosome copy number variant (CNV) was detected at multiple sites of the placenta after delivery. RESULTS: The husband was found to harbor heterozygous c.544-2A>G variant of the COL1A1 gene. The same variant was not detected in either of his parents. PGT revealed that out of three embryos of the couple, one was wild-type for the c.544-2A site but mosaicism for duplication of 16p13.3.11.2. The other two embryos were both heterozygous for the c.544-2A>G variant. Following adequate genetic counseling, the wild-type embryo was transplanted. Amniotic fluid testing confirmed that the fetus had normal chromosomes and did not carry the c.544-2A>G variant. The copy number of chromosomes at different parts of placenta was normal after birth. CONCLUSION: For couples affected with monogenic disorders, e.g., osteogenesis imperfecta, direct detection of the mutation site may be used for PGT after identifying the pathogenic variant. After adequate genetic counseling, prenatal diagnosis must be carried out to ensure the result.


Assuntos
Osteogênese Imperfeita , Diagnóstico Pré-Implantação , Aneuploidia , China , Feminino , Testes Genéticos , Humanos , Osteogênese Imperfeita/genética , Gravidez
3.
Sci Total Environ ; 807(Pt 1): 150814, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34626635

RESUMO

Due to strong endocrine disrupting effects, steroids in the environment have attracted substantial attention, with studies mostly focusing on the parent steroids. Here, we conducted the first investigation on the contamination profiles, possible sources, mass inventories, and ecological risks of 27 steroids and their metabolites in 15 typical fishing ports in Southeast China. Twelve steroids were detectable in the sediment samples with the total mean concentrations of 4.6-35 ng/g. High proportions of steroid metabolites were measured in the sediments and five metabolites were newly observed. Untreated municipal sewage and aquaculture wastes constitute the possible steroid sources in the studied fishing ports. The total inventories of steroids in fishing ports ranged from 2.1-16 mg/m2, with their metabolites being important contributors. The ecological risk analysis indicated high risks across all sampling sites mainly due to the contributions of parent steroids. Furthermore, our results found that progesterone is an acceptable chemical indicator for various steroids in sediments. This study provides the first evidence of steroid metabolites in the marine environment, calling for more studies in environmental behavior and ecotoxicology of steroid metabolites.


Assuntos
Monitoramento Ambiental , Poluentes Químicos da Água , Aquicultura , China , Sedimentos Geológicos , Esteroides/análise , Poluentes Químicos da Água/análise
4.
Clin Proteomics ; 18(1): 31, 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34963445

RESUMO

BACKGROUND: Placenta accreta (PA) is a major cause of maternal morbidity and mortality in modern obstetrics, few studies have explored the underlying molecular mechanisms. METHODS: In our study, transcriptome and proteome profiling were performed in placental tissues from ten participants including five cases each in the PA and control groups to clarify the pathogenesis of PA. RESULTS: We identified differential expression of 37,743 transcripts and 160 proteins between the PA and control groups with an overlap rate of 0.09%. The 33 most-significant transcripts and proteins were found and further screened and analyzed. Adhesion-related signature, chemotaxis related signatures and immune related signature were found in the PA group and played a certain role. Sum up two points, three significant indicators, methyl-CpG-binding domain protein 2 (MeCP2), podocin (PODN), and apolipoprotein D (ApoD), which participate in "negative regulation of cell migration", were downregulated at the mRNA and protein levels in PA group. Furthermore, transwell migration and invasion assay of HTR-8/SVneo cell indicated the all of them impaired the migration and invasion of trophoblast. CONCLUSION: A poor correlation was observed between the transcriptome and proteome data and MeCP2, PODN, and ApoD decreased in transcriptome and proteome profiling, resulting in increased migration of trophoblasts in the PA group, which clarify the mechanism of PA and might be the biomarkers or therapy targets in the future.

5.
IEEE Trans Biomed Eng ; PP2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34788216

RESUMO

In mammography, calcifications are one of the most common signs of breast cancer. Detection of such lesions is an active area of research for computer-aided diagnosis and machine learning algorithms. Due to limited numbers of positive cases, many supervised detection models suffer from overfitting and fail to generalize. We present a one-class, semi-supervised framework using a deep convolutional autoencoder trained with over 50,000 images from 11,000 negative-only cases. Since the model learned from only normal breast parenchymal features, calcifications produced large signals when comparing the residuals between input and reconstruction output images. As a key advancement, a structural dissimilarity index was used to suppress non-structural noises. Our selected model achieved pixel-based AUROC of 0.959 and AUPRC of 0.676 during validation, where calcification masks were defined in a semi-automated process. Although not trained directly on any cancers, detection performance of calcification lesions on 1,883 testing images (645 malignant and 1238 negative) achieved 75% sensitivity at 2.5 false positives per image. Performance plateaued early when trained with only a fraction of the cases, and greater model complexity or a larger dataset did not improve performance. This study demonstrates the potential of this anomaly detection approach to detect mammographic calcifications in a semi-supervised manner with efficient use of a small number of labeled images, and may facilitate new clinical applications such as computer-aided triage and quality improvement.

6.
Chemosphere ; : 132835, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34762885

RESUMO

Considering the adverse effects of heavy metals (HMs) on agriculture soil, in-situ immobilization has been paid great attention worldwide. P-modified biochar/hydrochar along with synthetic zeolite for efficient HMs immobilization in contaminated soil becomes a promising choice. In this study, H3PO4-modified hydrochar (BPH) derived from banana peels, and Na-X zeolite (ZL) prepared from coal gangue was applied individually and synergistically (1%BPH, 2%BPH 1%ZL, 2%ZL, and 1%BPH+1%ZL) to remediate a farmland soil polluted by Cd, Cu, and Pb near the coal-mining area. Compared with the mono-application of these two amendments, their combination significantly improved the soil organic carbon (SOC), electric conductivity (EC), and dehydrogenase activity. Besides, the addition of 1%CLH+1%ZL remarkably reduced the Cd, Cu, and Pb bioavailability by 67.01%, 57.01%, and 78.72%, respectively, in the soil after 100 d incubation by transforming these metals to more stable forms. The order of the HMs immobilization capacity for these two amendments was as follows: Pb > Cu > Cd. Moreover, the dominated immobilization mechanism of their synergistic application was that BPH could immobilize HMs by precipitation, complexation, and π-π electron-donor-acceptor interaction. The precipitation and complexation blocked the surface pores of BPH. The sustained release of phosphorus groups and radicals was prevented. This obstacle was possibly alleviated by adding ZL. Besides, the formation of cationic bridging, the enhancement of soil properties, and the physical adsorption of these amendments were also conducive to HMs immobilization in soil. This work indicated that co-application of BPH and ZL possibly was an excellent choice for immobilizing HMs in soil.

7.
Front Nutr ; 8: 750801, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778342

RESUMO

Background: Dairy product consumption is associated with ovarian cancer (OC) incidence. However, limited evidence is available on its influence on OC mortality. Methods: The association between pre-diagnostic dairy product intake and OC mortality was investigated in the OC follow-up study, which included a hospital-based cohort (n = 853) of women diagnosed with epithelial OC between 2015 and 2020. Pre-diagnosis diet information was collected using a validated food frequency questionnaire. Deaths were ascertained up to March 31, 2021 via death registry linkage. Cox proportional hazards model was used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI) for the aforementioned association. Results: A total of 130 women died during the median follow-up of 37.2 months (interquartile: 24.7-50.2 months). Comparisons of highest to lowest tertile intake showed that pre-diagnosis dairy product use was associated with total OC mortality (HR = 2.03, 95% CI = 1.21-3.40, p trend = 0.06). In addition, short survival was separately associated with protein (HR = 2.09, 95% CI = 1.25-3.49, p trend < 0.05), fat (HR = 2.16, 95% CI = 1.30-3.61, p trend < 0.05), and calcium (HR = 2.03, 95% CI = 1.21-3.4, p trend = 0.06) from dairy intake. Similar positive magnitudes were observed for menopausal status, residual lesions, histological type, and body mass index, although not all of these factors showed statistical significance. Conclusion: Pre-diagnosis dairy product consumption, including protein, fat, and calcium from dairy intake, was associated with higher mortality among OC survivors.

8.
Bioresour Technol ; : 126344, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34780901

RESUMO

The influences of combination of garbage enzyme and biochar on total organic carbon (TOC) degradation, humification and the fungal succession during sewage sludge (SS) composting were established. Results showed that the GE and BC + GE treatments significantly increased the enzyme activity of fluorescein diacetate hydrolase (FDA) and increased the TOC degradation rate by 9.8% and 21.9% relative to control. The excitation-emission matrix (EEM) combined with the percentage fluorescence response (Pi, n) also proved that the combination of BC and GE promoted fulvic acid-like and humic-like substances production, and thus increased humification. Furthermore, the combination of BC and GE effectively decreased the relative abundance of Unclassified_k_Fugni, while increased the abundance of Ascomycota and Basidiomycota compared with control. The four genera, Pseudeurotium, Talaromyces, Trichoderma, and Penicillium, were the main fungi for the humification. Comparatively, the combined of BC and GE showed the optimal performance for TOC degradation and humification during SS composting.

9.
Eur J Med Chem ; 226: 113877, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34624823

RESUMO

In humans, more than three hundred diverse enzymes that require zinc as an essential cofactor have been identified. These zinc enzymes have demonstrated different and important physiological functions and some of them have been considered as valuable therapeutic targets for drug discovery. Indeed, many drugs targeting a few zinc enzymes have been marketed to treat a variety of diseases. This review discusses drug discovery and drug development based on a dozen of zinc enzymes, including their biological functions and pathogenic roles, their best in class inhibitors (and clinical trial data when available), coordination and binding modes of representative inhibitors, and their implications for further drug design. The opportunities and challenges in developing zinc enzyme inhibitors for the treatment of human disorders are highlighted, too.

11.
Environ Sci Technol ; 55(22): 15090-15099, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34521203

RESUMO

Microbially derived extracellular polymeric substances (EPSs) occupy a large portion of dissolved organic matter (DOM) in surface waters, but the understanding of the photochemical behaviors of EPS is still very limited. In this study, the photochemical characteristics of EPS from different microbial sources (Shewanella oneidensis, Escherichia coli, and sewage sludge flocs) were investigated in terms of the production of reactive species (RS), such as triplet intermediates (3EPS*), hydroxyl radicals (•OH), and singlet oxygen (1O2). The steady-state concentrations of •OH, 3EPS*, and 1O2 varied in the ranges of 2.55-8.73 × 10-17, 3.01-4.56 × 10-15, and 2.08-2.66 × 10-13 M, respectively, which were within the range reported for DOM from other sources. The steady-state concentrations of RS varied among different EPS isolates due to the diversity of their composition. A strong photochemical degradation of the protein-like components in EPS isolates was identified by excitation emission matrix fluorescence with parallel factor analysis, but relatively, humic-like components remained stable. Fourier-transform ion cyclotron resonance mass spectrometry further revealed that the aliphatic portion of EPS was resistant to irradiation, while other portions with lower H/C ratios and higher O/C ratios were more susceptible to photolysis, leading to the phototransformation of EPS to higher saturation and lower aromaticity. With the phototransformation of EPS, the RS derived from EPS could effectively promote the degradation of antibiotic tetracycline. The findings of this study provide new insights into the photoinduced self-evolution of EPS and the interrelated photochemical fate of contaminants in the aquatic environment.


Assuntos
Matriz Extracelular de Substâncias Poliméricas , Esgotos , Radical Hidroxila , Fotólise , Shewanella
12.
Int J Dermatol ; 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34435665

RESUMO

BACKGROUND: Psoriasis is an immune-mediated inflammatory skin disease, featured by epidermal hyperproliferation. Psoriasis exhibits metabolic abnormalities, which can further aggravate the condition of psoriasis. The present study aimed to investigate the role of psoriatic keratinocytes (KCs) in the metabolic reprogramming of dermal mesenchymal stem cells (DMSCs). METHODS: Dermal mesenchymal stem cells were cocultured with primary KCs either from psoriatic lesions or from normal subjects using Transwell plate. Glycolysis and mitochondrial metabolism of DMSCs were detected by Seahorse Metabolic Analyzer. Expression levels of proteins were analyzed by Western blotting. DMSCs proliferation was assessed using 5-ethynyl-2'-deoxyuridine assay and Cell Counting Kit-8. RESULTS: In comparison with normal KCs, coculture of psoriatic KCs with DMSCs dramatically increased glycolytic and mitochondrial metabolism, and expression levels of stem cell factor, epidermal growth factor, glucose transporter 1, and c-Myc. Moreover, psoriatic KCs were more potent than normal KCs in the stimulation of DMSC proliferation. CONCLUSIONS: In conclusion, psoriatic KCs display a higher potency in metabolic reprogramming and stimulation of DMSC proliferation, possibly contributing to the pathogenesis of psoriasis. However, whether the intervention of metabolic reprogramming of DMSCs can alleviate psoriasis remains to be determined.

13.
Cancer Cell Int ; 21(1): 360, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238293

RESUMO

OBJECTIVE: Long non-coding RNAs (lncRNAs) and microRNAs (miRs) are differentially expressed in ovarian cancer (OC) cells and influence OC progression. This study intended to explore the underlying roles of LINC00115 and miR-30a in OC. METHODS: Gene Expression Omnibus database was used to find OC microarray datasets and bioinformatics analysis predicted the potential molecular mechanism of OC. OC stem cells (OCSCs) surface marker was isolated from human OC cell line and identified. CD133+ OCSCs were transfected with LINC00115, miR-30a and SOX9 alone or together to detect sphere-forming ability and apoptosis of OCSCs. Caspase-3 activity and DNA damage in cell supernatant were detected. The levels of CD44, NANOG, POU5F1, LINC00115, CD133, miR-30a and SOX9 were measured. Then sh-LNC00115-treated OCSCs were added with Wnt/ß-catenin activator SKL2001 to observe the changes of cell stemness and activity. Finally, animal models were established to evaluate the effect of LINC00115 on OCSC in vivo. RESULTS: LINC00115 and SOX9 were highly expressed in OC, while miR-30a was lowly expressed. After silencing LINC00115 or overexpressing miR-30a, the sphere-forming rate of CD133+ OCSC and levels of CD133, CD44, NANOG and POU5F1 decreased, while apoptotic rate, Caspase-3 activity and histone-related DNA damage increased. SOX9 reversed these trends. Additionally, LINC00115 could bind to miR-30a and miR-30a could target SOX9. SKL2001 partially reversed cell stemness and activity in sh-LNC00115-treated OCSCs. Finally, silencing LINC00115 could inhibit OCSCs growth in vivo. CONCLUSION: LINC00115 promoted stemness and inhibited apoptosis of OCSCs by upregulating SOX9 and in activating the Wnt/ß-catenin pathway through competitively binding to miR-30a.

14.
Front Pharmacol ; 12: 670054, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054541

RESUMO

Background: Emerging evidence suggests that gut microbiota plays a vital role in the occurrence of multiple endocrine disorders including polycystic ovary syndrome (PCOS). Shaoyao-Gancao Decoction (SGD), a classical Chinese prescription, has been widely used in the treatment of PCOS for decades. In previous studies, we found that SGD treatment could effectively reduce ovarian inflammation in PCOS rats. However, whether the anti-inflammation effect of SGD involves the regulation of the gut microbiota remains elusive. Methods: Letrozole-induced PCOS rat models were established, and the therapeutic effects of SGD were evaluated. Specifically, body weight, serum hormone concentrations, estrus phase and ovary histopathology were assessed. Then the structure of gut microbiota was determined by 16s rRNA sequencing. Additionally, the serum levels of pro-inflammatory cytokines and LPS were measured by ELISA kits. The key gene and protein expressions of TLR4/NF-κB signaling pathway were detected by quantitative real-time PCR and western blot. Results: SGD could effectively reduce body weight, regulate estrous cycles and ameliorate hyperandrogenism in PCOS rats. In addition, SGD treatment decreased releases of pro-inflammatory cytokines, enhanced the expressions of tight junction (occludin and claudin1), and then prevented a translocation of LPS into bloodstream. SGD could significantly reduce the ratio of Firmicutes to Bacteroidetes, decrease the abundance of LPS-producing pathogens Proteobateria and enrich the abundance of Butyricicoccus, Coprococcus, Akkermansia Blautia and Bacteroides in PCOS rats. Furthermore, SGD blunted the key gene and protein expressions of TLR4/NF-κB signaling pathway both in vivo and in LPS-induced RAW264.7 cells. Conclusion: SGD administration could ameliorate the inflammatory response in PCOS rats by remodeling gut microbiome structure, protecting gut barrier, and suppressing TLR4/NF-κB signaling pathway.

15.
Water Res ; 198: 117168, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33962238

RESUMO

Novel brominated flame retardants (NBFRs), which have been developed as replacements for legacy flame retardants such as polybrominated diphenyl ethers (PBDEs), are a class of alternative flame retardants with emerging and widespread applications. The ubiquitous occurrence of NBFRs in the aquatic environments and the potential adverse effects on aquatic organisms have initiated intense global concerns. The present article, therefore, identifies and analyzes the current state of knowledge on the occurrence, bioaccumulation, fates, and environmental and health risks of NBFRs in aquatic environments. The key findings from this review are that (1) the distribution of NBFRs are source-dependent in the global aquatic environments, and several NBFRs have been reported at higher concentrations than that of the legacy flame retardants; (2) high bioaccumulative properties have been found for all of the discussed NBFRs due to their strong hydrophobic characteristics and weak metabolic rates; (3) the limited information available suggests that NBFRs are resistant to biotic and abiotic degradation processes and that sorption to sludge and sediments are the main fate of NBFRs in the aquatic environments; (4) the results of ecological risk assessments have indicated the potential risks of NBFRs and have suggested that source areas are the most vulnerable environmental compartments. Knowledge gaps and perspectives for future research regarding the monitoring, toxicokinetics, transformation processes, and development of ecological risk assessments of NBFRs in aquatic environments are proposed.


Assuntos
Retardadores de Chama , Hidrocarbonetos Bromados , Bioacumulação , Monitoramento Ambiental , Retardadores de Chama/análise , Éteres Difenil Halogenados , Medição de Risco
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 615-619, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33812440

RESUMO

OBJECTIVE: To compare the plasma components of frozen plasma (FP) and fresh frozen plasma (FFP). METHODS: Twenty samples of FP and 20 samples of FFP from Beijing Red Cross Blood Center were randomly selected. Immediately after plasma melting, 12 plasma components including coagulation factor, fibrinolytic system and anticoagulation protein were detected, including activated partial thromboplastin time (APTT), prothrombin time (PT), coagulation factor Ⅷ (FⅧ) activity, coagulation factor Ⅴ (FⅤ) activity, fibrinogen(FIB) level, ADAMTS-13 activity, von Willebrand factor(vWF) activity, D-dimer (D-dimer, DD), fibrin degradation products (FDP), antithrombin (AT), protein C (PC), and protein S (PS). All these coagulation components between the two types of plasma were compared and analyzed. RESULTS: Compared with FFP, APTT in FP was significantly prolonged(t=3.428, P<0.01), and PT was also significantly prolonged(z=-2.140, P<0.05), and FⅧ activity was decreased (t=-3.372, P<0.01), but all in the reference range, and PS activity was decreased(t=-2.458,P<0.05), there was no statistical difference in the other part between two types of plasma(P>0.05). CONCLUSION: FP can substitute FFP in the treatment of some diseases, although it is lack of some coagulation factors and anticoagulation protein.


Assuntos
Fatores de Coagulação Sanguínea , Plasma , Pequim , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Humanos
17.
Acta Odontol Scand ; 79(6): 458-465, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33823749

RESUMO

OBJECTIVES: Odontogenic inflammatory diseases are main causes for alveolar bone breakdown and teeth loss, leaving great difficulties in denture restoration. Local inflammatory granulation tissue (IGT) is considered as pathological tissue and required to be removed. However, there are many evidences supporting that under appropriate intervention, IGT in alveolar bone maybe transformed into reparative granulation tissue (RGT), followed by ossification. Therefore, this study aimed to discover a specific target to promote this transformation. MATERIALS AND METHODS: After drawing out histological differences between IGT and RGT with haematoxylin and eosin (H&E) and immunohistochemical (IHC) assay staining, TMT-labelled quantitative proteomic analysis was applied to identify potential targets. RESULTS: The most striking histological property of RGT was found to be ECM deposition, which significantly decreased inflammatory cells, prominently increased fibroblasts as well as triggered changes of vascular types. Combined with histological findings and proteomic analysis, five KEGG pathways were associated with ECM, inflammation and angiogenesis and 49 pathways involved in differentially expressed proteins. COL1A1 was not only the most up-regulated protein, but also one of main hubs in protein-protein interaction regulatory network. Specific protease cathepsin K (CTSK) was identified. Level of CTSK in RGT was down-regulated to 69.10-76.97% (p < .05), with significantly up-regulated COL1A1, COL1A2, FN1 and TGFB1 included in focal adhesion, PI3K-Akt signalling pathways and angiogenesis. CTSK involved in transformation from IGT to RGT. CONCLUSIONS: CTSK might be a target to regulate transformation from IGT to RGT in alveolar bone through ECM, stem cells and angiogenesis mechanisms. However, further research is also clearly required.


Assuntos
Fosfatidilinositol 3-Quinases , Proteômica , Tecido de Granulação , Humanos , Osteogênese , Células-Tronco
18.
ACS Appl Mater Interfaces ; 13(17): 19679-19694, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33876926

RESUMO

Photothermal therapy (PTT) is a promising tumor therapy strategy; however, heterogeneous heat distribution over the tumor often exists, resulting in insufficient photothermal ablation and potential risk of cancer metastasis, which has been demonstrated to be associate with platelets. Herein, a near-infrared (NIR) photothermal agent of IR780 was conjugated with MRI agent of Gd-DOTA via a disulfide linkage (ICD-Gd), which was coassembly with lipid connecting tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) (DSPE-PEG-CREKA) to encapsulate a platelet inhibitor of ticagrelor (Tic), affording a multistimuli-responsive nanosystem (DPC@ICD-Gd-Tic). The nanosystem with completely quenching fluorescence could specifically target the tumor-associated platelets and showed pH/reduction/NIR light-responsive drug release, which simultaneously resulting in dis-assembly of nanoparticle and fluorescence recovery, enabling the drug delivery visualization in tumor in situ via activatable NIR fluorescence/MR bimodal imaging. Finally, DPC@ICD-Gd-Tic further integrated the photoinduced hyperthermia and platelet function inhibitor to achieve synergistic anticancer therapy, leading to ablation of primary tumor cells and effectively suppressed their distant metastasis. The number of lung metastases in 4T1 tumor bearing mice was reduced by about 90%, and the size of tumor was reduced by about 70%, while half of the mouse was completely cured by this smart nanosystem.


Assuntos
Imageamento por Ressonância Magnética/métodos , Metástase Neoplásica/prevenção & controle , Imagem Óptica/métodos , Terapia Fototérmica , Inibidores da Agregação Plaquetária/administração & dosagem , Ticagrelor/administração & dosagem , Animais , Linhagem Celular Tumoral , Terapia Combinada , Sistemas de Liberação de Medicamentos , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Bioorg Med Chem Lett ; 43: 128051, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33887441

RESUMO

Successes have been achieved in developing human monoamine oxidase B (hMAO-B) inhibitors as anti-Parkinson's disease (PD) drugs. However, low efficiency and unwanted side effects of the marketed hMAO-B inhibitors hamper their medical applications, therefore, novel potent selective hMAO-B inhibitors are still of great interest. Herein we report 1-(prop-2-yn-1-ylamino)-2,3-dihydro-1H-indene-4-thiol derivatives as hMAO-B inhibitors, which were designed by employing a fragment-based drug design strategy to link rasagiline to hydrophobic fragments. Among the synthesized 31 compounds, K8 and K24 demonstrated very encouraging hMAO-B inhibitory activities and selectivity over hMAO-A, better than rasagiline and safinamide. In vitro studies indicated that K8 and K24 are nontoxic to nervous tissue cells and they have considerable effects against ROS formation and potential neuroprotective activity. Further mice behavioral tests demonstrated these two compounds have good therapeutic effects on MPTP-induced PD model mice. All these experiment results suggest that compounds K8 and K24 can be promising candidates for further research for treatment of PD.


Assuntos
Desenho de Fármacos , Indenos/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Compostos de Sulfidrila/farmacologia , Relação Dose-Resposta a Droga , Humanos , Indenos/síntese química , Indenos/química , Modelos Moleculares , Estrutura Molecular , Inibidores da Monoaminoxidase/síntese química , Inibidores da Monoaminoxidase/química , Relação Estrutura-Atividade , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/química
20.
Hepatology ; 74(1): 214-232, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33615520

RESUMO

BACKGROUND AND AIMS: Bone is the second most frequent site of metastasis for HCC, which leads to an extremely poor prognosis. HCC bone metastasis is typically osteolytic, involving the activation of osteoclasts. Long noncoding RNA H19 plays an important role in the pathogenesis of human cancers. Nonetheless, the mechanism underlying the participation of H19 in HCC bone metastasis remains unclear. APPROACH AND RESULTS: The current study established a mouse HCC bone metastasis model by using serial intracardiac injection and cell isolation to obtain cells with distinct bone metastasis ability. H19 was highly expressed in these cells and in clinical HCC bone metastasis specimens. Both osteoclastogenesis in vitro and HCC bone metastasis in vivo were promoted by H19 overexpression, whereas these processes were suppressed by H19 knockdown. H19 overexpression attenuated p38 phosphorylation and further down-regulated the expression of osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor. However, up-regulated OPG expression as well as suppressed osteoclastogenesis caused by H19 knockdown were recovered by p38 interference, indicating that p38 mitogen-activated protein kinase (MAPK)-OPG contributed to H19-promoted HCC bone metastasis. Furthermore, we demonstrated that H19 inhibited the expression of OPG by binding with protein phosphatase 1 catalytic subunit alpha (PPP1CA), which dephosphorylates p38. SB-203580-mediated inactivation of p38MAPK reversed the down-regulation of HCC bone metastasis caused by H19 knockdown in vivo. Additionally, H19 enhanced cell migration and invasion by up-regulating zinc finger E-box binding homeobox 1 through the sequestration of microRNA (miR) 200b-3p. CONCLUSIONS: H19 plays a critical role in HCC bone metastasis by reducing OPG expression, which is mediated by the PPP1CA-induced inactivation of the p38MAPK pathway; and H19 also functions as a sponge for miR-200b-3p.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...