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1.
Adv Exp Med Biol ; 1280: 1-18, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791971

RESUMO

Due to the great diversity of chemical and physical properties of metabolites as well as a wide range of concentrations of metabolites present in metabolomic samples, performing comprehensive and quantitative metabolome analysis is a major analytical challenge. Conventional approach of combining various techniques and methods with each detecting a fraction of the metabolome can lead to the increase in overall metabolomic coverage. However, this approach requires extensive investment in equipment and analytical expertise with still relatively low coverage and low sample throughput. Chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS) offers an alternative means of increasing metabolomic coverage while maintaining high quantification precision and accuracy. This chapter describes the CIL LC-MS method and its key features for metabolomic analysis.


Assuntos
Metabolômica , Espectrometria de Massas em Tandem , Cromatografia Líquida , Marcação por Isótopo , Metaboloma
2.
Nanotechnology ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33799309

RESUMO

Various polydopamine (PDA) nanospheres were synthesized by utilizing triblock copolymer Pluronic F127 and 1,3,5-trimethylbenzene (TMB) as soft templates. Precise morphology control of polydopamine nanospheres was realized from solid polydopamine nanospheres (PDANSs) to hollow polydopamine nanospheres (H-PDANSs), mesoporous polydopamine nanospheres (MPDANSs) and hollow mesoporous polydopamine nanospheres (H-MPDANSs) by adjusting the weight ratio of TMB to F127. The inner diameter of the prepared H-MPDANSs can be controlled in the range of 50-100 nm, and the outer diameter is about 180 nm. Furthermore, the thickness of hollow mesoporous spherical shell can be adjusted by changing the amount of dopamine (DA). The H-MPDANSs have good biocompatibility, excellent photothermal properties, high drug loading capacity, and outstanding sustainable drug release properties. In addition, both NIR laser irradiation and acid pH can facilitate the controlled release of doxorubicin (DOX) from H-MPDANSs@DOX.

3.
Mol Med Rep ; 23(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33760140

RESUMO

Chaperone­mediated autophagy (CMA) is a selective type of autophagy whereby a specific subset of intracellular proteins is targeted to the lysosome for degradation. The present study investigated the mechanisms underlying the response and resistance to 5­fluorouracil (5­FU) in colorectal cancer (CRC) cell lines. In engineered 5­FU­resistant CRC cell lines, a significant elevation of lysosome­associated membrane protein 2A (LAMP2A), which is the key molecule in the CMA pathway, was identified. High expression of LAMP2A was found to be responsible for 5­FU resistance and to enhance PLD2 expression through the activation of NF­κB pathway. Accordingly, loss or gain of function of LAMP2A in 5­FU­resistant CRC cells rendered them sensitive or resistant to 5­FU, respectively. Taken together, the results of the present study suggested that chemoresistance in patients with CRC may be mediated by enhancing CMA. Thus, CMA is a promising predictor of chemosensitivity to 5­FU treatment and anti­CMA therapy may be a novel therapeutic option for patients with CRC.

4.
Sci Rep ; 11(1): 6422, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33742041

RESUMO

Coronavirus disease 2019 (COVID-19) has spread in more than 100 countries and regions around the world, raising grave global concerns. COVID-19 has a similar pattern of infection, clinical symptoms, and chest imaging findings to influenza pneumonia. In this retrospective study, we analysed clinical and chest CT data of 24 patients with COVID-19 and 79 patients with influenza pneumonia. Univariate analysis demonstrated that the temperature, systolic pressure, cough and sputum production could distinguish COVID-19 from influenza pneumonia. The diagnostic sensitivity and specificity for the clinical features are 0.783 and 0.747, and the AUC value is 0.819. Univariate analysis demonstrates that nine CT features, central-peripheral distribution, superior-inferior distribution, anterior-posterior distribution, patches of GGO, GGO nodule, vascular enlargement in GGO, air bronchogram, bronchiectasis within focus, interlobular septal thickening, could distinguish COVID-19 from influenza pneumonia. The diagnostic sensitivity and specificity for the CT features are 0.750 and 0.962, and the AUC value is 0.927. Finally, a multivariate logistic regression model combined the variables from the clinical variables and CT features models was made. The combined model contained six features: systolic blood pressure, sputum production, vascular enlargement in the GGO, GGO nodule, central-peripheral distribution and bronchiectasis within focus. The diagnostic sensitivity and specificity for the combined features are 0.87 and 0.96, and the AUC value is 0.961. In conclusion, some CT features or clinical variables can differentiate COVID-19 from influenza pneumonia. Moreover, CT features combined with clinical variables had higher diagnostic performance.


Assuntos
/diagnóstico , Influenza Humana/diagnóstico , Pneumonia Viral/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Influenza Humana/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico por imagem , Estudos Retrospectivos , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto Jovem
5.
Front Public Health ; 9: 630620, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33692982

RESUMO

The outbreak of coronavirus disease-2019 (COVID-19) ineluctably caused social distancing and unemployment, which may bring additional health risks for patients with cancer. To investigate the association of the pandemic-related impacts with the health-related quality of life (HRQoL) among patients with melanoma during the COVID-19 pandemic, we conducted a cross-sectional study among Chinese patients with melanoma. A self-administered online questionnaire was distributed to melanoma patients through social media. Demographic and clinical data, and pandemic-related impacts (unemployment and income loss) were collected. HRQoL was determined by the Functional Assessment of Cancer Therapy-General (FACT-G) and its disease-specific module (the melanoma subscale, MS). A total of 135 patients with melanoma completed the study. The mean age of the patients was 55.8 ± 14.2 years, 48.1% (65/135) were male, and 17.04% (34/135) were unemployed since the epidemic. Unemployment of the patients and their family members and income loss were significantly associated with a lower FACT-G score, while the MS score was associated with the unemployment of the patients' family members. Our findings suggested that unemployment is associated with impaired HRQoL in melanoma patients during the COVID-19 epidemic.


Assuntos
Grupo com Ancestrais do Continente Asiático/psicologia , /psicologia , Melanoma/economia , Melanoma/psicologia , Qualidade de Vida/psicologia , Desemprego/psicologia , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Melanoma/epidemiologia , Pessoa de Meia-Idade , Pandemias , Inquéritos e Questionários , Desemprego/estatística & dados numéricos
6.
Exp Dermatol ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33751677

RESUMO

Symptomatic dermographism (SD) is a recurrent inflammatory skin disease related to immunity; however, the details remain elusive. In view of the important role of gut microbiota in immune regulation, the purpose of this study is to investigate the alterations of gut microbiota in SD and explore the potential bacterial biomarkers for diagnosis. A case-control study including SD patients and normal controls (NCs) was carried out. Gut microbiota of the participants was analysed by the 16S rDNA sequencing of faecal samples. The linear discriminant analysis effect size and the receiver operating characteristic curve (ROC) analysis were used to identify the bacterial biomarkers. Forty-four participants were included in this study. The alpha-diversity and beta-diversity of gut microbiota differed significantly between SD patients and NCs. The abundance of Verrucomicrobia, Ruminococcaceae and their subordinate taxa were reduced in SD patients, while Enterobacteriales and its subordinate taxon exhibited higher relative abundance compared with NCs. Subdoligranulum and Ruminococcus bromii showed a potential diagnostic value for SD, and Prevotella stercorea was negatively relevant to duration of SD. Furthermore, the pyruvate, butyric acid and histamine metabolism pathway were likely to be involved in the pathogenesis of SD. Our results revealed that the gut microbiota of SD patients experienced obvious changes, and Verrucomicrobia, Ruminococcaceae and Enterobacteriales were microbiota signatures for SD.

7.
Chemosphere ; 269: 128677, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33657748

RESUMO

Toxicity of microplastics (MPs) in granular form to aquatic animals has been frequently tested, whereas the effects of fibrous MPs remain further explored. In this study, the effects of polyethylene terephthalate granular particles (p-PET, approximately 150 µm in diameter) and fibers (f-PET, approximately 3-5 mm in length and 20 µm in diameter) on the development of zebrafish embryos and their joint effects with cadmium (Cd) were compared. p-PET and f-PET accelerated the velocities of blood flow and heart rate and inhibited hatching in zebrafish embryos because of their barrier effects on the channels in the embryonic chorion and enhanced the mechanical strength of the chorion. The Cd content in the chorion increased by p-PET due to the adsorption of p-PET on the chorion. By contrast, more f-PET dissociated in culture medium and resulted in low Cd content in the chorion. Given that chorion can effectively block p-PET and f-PET, the Cd accumulation in eggs significantly decreased (p < 0.05) under p-PET/f-PET and Cd combined treatment because of the reduction in the bioavailability of Cd. Therefore, p-PET and f-PET decreased the toxicities of Cd on all the target endpoints in this study, and the detoxification effect of f-PET at 72 hpf was more significant than that of p-PET. These results suggest that the toxicity induced by MPs might be form-related.


Assuntos
Microplásticos , Poluentes Químicos da Água , Animais , Cádmio/toxicidade , Córion , Embrião não Mamífero , Plásticos/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
8.
Diagn Interv Radiol ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33650498

RESUMO

During the coronavirus disease 2019 (COVID-19) pandemic period, container computed tomography (CT) scanners were developed and used for the first time in China to perform CT examinations for patients with clinically mild to moderate COVID-19 who did not need to be hospitalized for comprehensive treatment, but needed to be isolated in Fangcang shelter hospitals (also known as makeshift hospitals) to receive some supportive treatment. The container CT is a multidetector CT scanner installed within a radiation-protected stand-alone container (a detachable lead shielding room) that is deployed outside the makeshift hospital buildings. The container CT approach provided various medical institutions with the solution not only for rapid CT installation and high adaptability to site environments, but also for significantly minimizing the risk of cross-infection between radiological personnel and patients during CT examination in the pandemic. In this article, we described the typical setup of a container CT and how it worked for chest CT examinations in Wuhan city, the epicenter of COVID-19 outbreak.

9.
Eur Urol ; 2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33785255

RESUMO

CONTEXT: In addition to genetic alterations, epigenetic alterations play a crucial role during prostate cancer progression. A better understanding of the epigenetic factors that promote prostate cancer progression may lead to the design of rational therapeutic strategies to target prostate cancer more effectively. OBJECTIVE: To systematically review recent literature on the role of epigenetic factors in prostate cancer and highlight key preclinical and translational data with epigenetic therapies. EVIDENCE ACQUISITION: We performed a systemic literature search in PubMed. At the request of the editors, we limited our search to articles published between January 2015 and August 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Clinical trials targeting epigenetic factors were retrieved from clinicaltrials.gov. EVIDENCE SYNTHESIS: We retrieved 1451 articles, and 62 were finally selected for review. Twelve additional foundational studies outside this time frame were also included. Findings from both preclinical and clinical studies were reviewed and summarized. We also discuss 12 ongoing clinical studies with epigenetic targeted therapies. CONCLUSIONS: Epigenetic mechanisms impact prostate cancer progression. Understanding the role of specific epigenetic factors is critical to determine how we may improve prostate cancer treatment and modulate resistance to standard therapies. Recent preclinical studies and ongoing or completed clinical studies with epigenetic therapies provide a useful roadmap for how to best deploy epigenetic therapies clinically to target prostate cancer. PATIENT SUMMARY: Epigenetics is a process by which gene expression is regulated without changes in the DNA sequence itself. Oftentimes, epigenetic changes influence cellular behavior and contribute to cancer development or progression. Understanding how epigenetic changes occur in prostate cancer is the first step toward therapeutic targeting in patients. Importantly, laboratory-based studies and recently completed and ongoing clinical trials suggest that drugs targeting epigenetic factors are promising. More work is necessary to determine whether this class of drugs will add to our existing treatment arsenal in prostate cancer.

10.
Mol Cell Endocrinol ; 528: 111223, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33667596

RESUMO

The transcription factor GLIS3 is an important factor in hormone biosynthesis and thyroid development, and mutations in GLIS3 are relatively rare. Deletions of more than one of the 11 exons of GLIS3 occur in most patients with various extrathyroidal abnormalities and congenital hypothyroidism (CH), and only 18 missense variants of GLIS3 related to thyroid disease have been reported. The aim of this study was to report the family history and molecular basis of patients with CH who carry GLIS3 variants. Three hundred and fifty-three non-consanguineous infants with CH were recruited and subjected to targeted exome sequencing of CH-related genes. The transcriptional activity and cellular localization of the variants in GLIS3 were investigated in vitro. We identified 20 heterozygous GLIS3 exonic missense variants, including eight novel sites, in 19 patients with CH. One patient carried compound heterozygous GLIS3 variants (p.His34Arg and p.Pro835Leu). None of the variants affected the nuclear localization. However, three variants (p.His34Arg, p.Pro835Leu, and p.Ser893Phe) located in the N-terminal and C-terminal regions of the GLIS3 protein downregulated the transcriptional activation of several genes required for thyroid hormone (TH) biosynthesis. This study of patients with CH extends the current knowledge surrounding the spectrum of GLIS3 variants and the mechanisms by which they cause TH biosynthesis defects.

11.
Medicine (Baltimore) ; 100(9): e24462, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655918

RESUMO

INTRODUCTION: Numerous investigations have been performed to explore candidate biomarker proteins in esophageal squamous cell carcinoma (ESCC) patients, which could predict the response to chemoradiotherapy (CRT). Here we report a patient with unresectable ESCC who had unsatisfactory effects with radiotherapy, chemotherapy and immunotherapy. We performed genetic analysis in this patient to gain insights about the cause of the rapid progression. PATIENT CONCERNS: A 65-year-old man presented with food obstruction, hoarse voice and choking on drinking water for 2 months, and pain behind the breastbone for 1 month. DIAGNOSIS: The patient was clinically diagnosed with ESCC and staged as T4N1M1 Stage IV. INTERVENTIONS: The patient was treated with CRT and immunotherapy. Mutational analyses through high throughput DNA sequencing methodology (next generation sequencing; NGS) was performed on the patient's blood sample. OUTCOMES: The tumor progressed rapidly during the treatment period, and the patient passed away only 3 months from the onset of symptoms. CONCLUSION: Although the role of TP53 gene and PIK3CA gene in the progression, treatment and sensitivity of esophageal cancer has been studied, the mechanism of their simultaneous appearance has not been demonstrated in relevant studies. We speculate that the reason for the rapid progression in this patient during active treatment might be related to this. Further studies are needed to validate our observations.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Genes p53/genética , Idoso , Análise Mutacional de DNA , Progressão da Doença , Evolução Fatal , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino
12.
Food Chem ; 352: 129332, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33690075

RESUMO

In order to construct a novel and efficient calcium delivery system, a dextran- casein phosphopeptide (CPP) conjugates as calcium carrier was prepared by Maillard reaction of CPP and dextran. The preparation of the conjugates, construction of calcium delivery system and digestion in vitro were studied. The grafting rate of conjugates, which was confirmed by migration and intensity changes in the characteristic peaks using ultraviolet-visible and Fourier transform infrared spectroscopy, reached 48.88%. The microscopy showed CPP was coated with dextran, the conjugates with a kind of "shell-core" structure had excellent stability. Compared with CPP, the chelating rate of conjugates increased from 6.0% to 13.87%, and the calcium retention rate improved from 1.09% to 7.90% in vitro digestion. The calcium binding capacity and effect of controlled release of the conjugates were superior to those of CPP. Therefore, the conjugates could be used as an effective carrier for new calcium supplements.


Assuntos
Cálcio/química , Caseínas/química , Dextranos/química , Digestão , Portadores de Fármacos/química , Fosfopeptídeos/química , Cálcio/metabolismo , Reação de Maillard
13.
Biosens Bioelectron ; 179: 113052, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33601131

RESUMO

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are prominent metabolic products which show well-established significance. At relatively low concentrations, they play multifaceted roles in regulating a number of physiological processes. Overproduction of ROS/RNS contributes to the pathogenesis of a plethora of physiological disorders, including but not limited to cardiovascular diseases, neurodegenerative diseases, cancer. Electrochemistry have been extensively used for detecting and monitoring ROS/RNS, benefiting from their inherent advantages including fast response, low costs, real-time detection, high sensitivity and selectivity. This review focuses on three types of ROS/RNS (H2O2, O2-, NO) with emphasis on their electrochemical detection/monitoring respectively. We demonstrate the application of electrochemical strategies for ROS/RNS detection in body fluids, in vitro, and in vivo, outlining the hardware architecture and comparing analytical performance of these sensors. This review aims for a holistic view of limitations in existing ROS/RNS detection by comprehensively explaining the shortcomings of the current works in the hope of drawing attentions to the challenges of ROS/RNS electrochemical technologies. We pay particular attention to in vitro and in vivo sensors and extend our evaluation to suggest possible solutions. Specifically, this review focuses on the development of currently nanotechnologies, biomimetic engineering, 3D-culture methods and implanted sensors to provide a guideline for future works.

14.
BMC Plant Biol ; 21(1): 81, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557757

RESUMO

BACKGROUND: Calcium (Ca2+) plays an important role in plant growth and development, and the maintenance of calcium homeostasis is necessary for the survival of all plant species. Ca2+/H+ exchangers (CAXs) are a subgroup of the CaCA (Ca2+/cation antiporter) superfamily. In general, CAX proteins mediate cytosolic Ca2+ entry into vacuoles to prevent excessive accumulation of Ca2+ in the cytosol. The CaCA superfamily has been identified and characterised in many plant species; however, characterisation of the CaCA superfamily and functional study of apple CAX proteins have yet to be conducted in apple (Malus × domestica Borkh.). RESULTS: Here, we identified 21 CaCA family proteins in apple for the first time. Phylogenetic and gene structure analysis, as well as prediction of conserved motifs, suggested that these proteins could be classified into four groups: CAX, CCX, NCL, and MHX. Expression analysis showed that the 10 MdCAX genes we cloned strongly responded to calcium and abiotic stress treatments. Collinearity analysis and characterisation of calcium transport capacity resulted in the identification of a pair of segmental duplication genes: MdCAX3L-1 and MdCAX3L-2; MdCAX3L-2 showed strong calcium transport capacity, whereas MdCAX3L-1 showed no calcium transport capacity. Yeast two-hybrid (Y2H) assays showed that these two proteins could interact with each other. The high sequence similarity (94.6%) makes them a good model for studying the crucial residues and structural basis of the calcium transport of CAX proteins. Prediction of the protein interaction network revealed several proteins that may interact with CAX proteins and play important roles in plant stress responses, such as SOS2, CXIP1, MHX, NRAMP3, and MTP8. CONCLUSIONS: Our analysis indicated that MdCAX proteins have strong calcium transport capacity and are involved in the abiotic stress response in apple. These findings provide new insight and rich resources for future studies of MdCAX proteins in apple.

15.
BMC Cancer ; 21(1): 141, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557782

RESUMO

BACKGROUND: Lung carcinoid is a rare malignant tumor with poor survival. The current study established a nomogram model for predicting cancer-specific survival (CSS) in patients with lung carcinoid tumors. METHODS: A total of 1956 patients diagnosed with primary lung carcinoid tumors were extracted from the Surveillance, Epidemiology, and End Results database. The specific predictors of CSS for lung carcinoid tumors were identified and integrated to build a nomogram. Validation of the nomogram was conducted using parameters concordance index (C-index), calibration plots, decision curve analyses (DCAs), and the receiver operating characteristic (ROC) curve. RESULTS: Age at diagnosis, grade, histological type, N stage, M stage, surgery of the primary site, radiation of the primary site, and tumor size were independent prognostic factors of CSS. High discriminative accuracy of the nomogram model was shown in the training cohort (C-index = 0.873), which was also testified in the internal validation cohort (C-index = 0.861). In both cohorts, the calibration plots showed good concordance between the predicted and observed CSS at 3, 5, and 10 years. The DCA showed great potential for clinical application. The ROC curve showed superior survival predictive ability of the nomogram model (area under the curve = 0.868). CONCLUSIONS: We developed a practical nomogram that provided independent predictions of CSS for patients with lung carcinoid tumors. This nomogram may have the potential to assist clinicians in prognostic evaluations or developing individualized therapies for patients with this neoplasm.

17.
JAMA Oncol ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33570548

RESUMO

Importance: Decipher (Decipher Biosciences Inc) is a genomic classifier (GC) developed to estimate the risk of distant metastasis (DM) after radical prostatectomy (RP) in patients with prostate cancer. Objective: To validate the GC in the context of a randomized phase 3 trial. Design, Setting, and Participants: This ancillary study used RP specimens from the phase 3 placebo-controlled NRG/RTOG 9601 randomized clinical trial conducted from March 1998 to March 2003. The specimens were centrally reviewed, and RNA was extracted from the highest-grade tumor available in 2019 with a median follow-up of 13 years. Clinical-grade whole transcriptomes from samples passing quality control were assigned GC scores (scale, 0-1). A National Clinical Trials Network-approved prespecified statistical plan included the primary objective of validating the independent prognostic ability of GC for DM, with secondary end points of prostate cancer-specific mortality (PCSM) and overall survival (OS). Data were analyzed from September 2019 to December 2019. Intervention: Salvage radiotherapy (sRT) with or without 2 years of bicalutamide. Main Outcomes and Measures: The preplanned primary end point of this study was the independent association of the GC with the development of DM. Results: In this ancillary study of specimens from a phase 3 randomized clinical trial, GC scores were generated from 486 of 760 randomized patients with a median follow-up of 13 years; samples from a total of 352 men (median [interquartile range] age, 64.5 (60-70) years; 314 White [89.2%] participants) passed microarray quality control and comprised the final cohort for analysis. On multivariable analysis, the GC (continuous variable, per 0.1 unit) was independently associated with DM (hazard ratio [HR], 1.17; 95% CI, 1.05-1.32; P = .006), PCSM (HR, 1.39; 95% CI, 1.20-1.63; P < .001), and OS (HR, 1.17; 95% CI, 1.06-1.29; P = .002) after adjusting for age, race/ethnicity, Gleason score, T stage, margin status, entry prostate-specific antigen, and treatment arm. Although the original planned analysis was not powered to detect a treatment effect interaction by GC score, the estimated absolute effect of bicalutamide on 12-year OS was less when comparing patients with lower vs higher GC scores (2.4% vs 8.9%), which was further demonstrated in men receiving early sRT at a prostate-specific antigen level lower than 0.7 ng/mL (-7.8% vs 4.6%). Conclusions and Relevance: This ancillary validation study of the Decipher GC in a randomized trial cohort demonstrated association of the GC with DM, PCSM, and OS independent of standard clinicopathologic variables. These results suggest that not all men with biochemically recurrent prostate cancer after surgery benefit equally from the addition of hormone therapy to sRT. Trial Registration: ClinicalTrials.gov identifier: NCT00002874.

18.
Bioorg Chem ; 108: 104656, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33548731

RESUMO

In this study, we report the generation of a polymer-based dynamic combinatorial library (DCL) incorporating exchangeable side chains using acylhydrazone formation reaction. In combination with tetrameric butyrylcholinesterase (BChE), the most potent binding side chain was identified, and the information obtained was further used for the synthesis of a multivalent BChE inhibitor. In the in vitro biological evaluation, this multivalent inhibitor exhibited not only better inhibitory effect than the commercial reference but also high selectivity on BChE over acetylcholinesterase (AChE).

19.
Food Chem ; 349: 129202, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33582540

RESUMO

In this work, we propose a electrochemical enzyme-free glucose sensor by direct growth of conductive Ni/Co bimetal MOF on carbon cloth [Ni/Co(HHTP)MOF/CC] via a facile hydrothermal method. Due to excellent conductivity between Ni/Co(HHTP)MOF and CC, synergic catalytic effect of Ni and Co elements, the Ni/Co(HHTP)MOF/CC not only provides larger surface area and more effective active sites, but also boosts the charge transports and electro-catalytic performance. Under optimized conditions, the Ni/Co(HHTP)MOF/CC shows excellent activity with a linear range of 0.3 µM-2.312 mM, a low detection limit of 100 nM (S/N = 3), a fast response time of 2 s and a high sensitivity of 3250 µA mM-1 cm-2. Furthermore, the Ni/Co(HHTP)MOF/CC was successfully applied for the detection of glucose in real serum and beverages with competitive performances. This facile and cost-effective method provides a novel strategy for monitoring of glucose in biological and food samples.


Assuntos
Bebidas/análise , Carbono/química , Cobalto/química , Eletroquímica/instrumentação , Glucose/análise , Estruturas Metalorgânicas/química , Níquel/química , Glicemia/análise , Catálise , Condutividade Elétrica , Humanos , Limite de Detecção
20.
Anticancer Drugs ; 32(3): 314-322, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33394687

RESUMO

Evodiamine (Evo), a quinazoline alkaloid and one of the most typical polycyclic heterocycles, is mainly isolated from Evodia rugulosa. Vasculogenic mimicry (VM) is a newly identified way of angiogenesis during tumor neovascularization, which is prevalent in a variety of highly invasive tumors. The purpose of this study was to investigate the effect and mechanism of Evo on VM in human colorectal cancer (CRC) cells. The number of VM structures was calculated by the three-dimensional culture of human CRC cells. Wound-healing was used to detect the migration of HCT116 cells. Gene expression was detected by reverse transcription-quantitative PCR assay. CD31/PAS staining was used to identify VM. Western blotting and immunofluorescence were used to detect protein levels. The results showed that Evo inhibited the migration of HCT116 cells, as well as the formation of VM. Furthermore, Evo reduced the expression of hypoxia-inducible factor 1-alpha (HIF-1α), VE-cadherin, VEGF, MMP2, and MMP9. In a model of subcutaneous xenotransplantation, Evo also inhibited tumor growth and VM formation. Our study demonstrates that Evo could inhibit VM in CRC cells HCT116 and reduce the expression of HIF-1α, VE-cadherin, VEGF, MMP2, and MMP9.

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