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1.
Mol Pharm ; 21(2): 895-903, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38170629

RESUMO

To develop radiolabeled FGFR2-targeting probes for visualizing fibroblast growth factor receptor (FGFR) expression levels in the tumor microenvironment, four novel 99mTc-labeled FGFR2-targeting peptides ([99mTc]Tc-FGFR2-1, [99mTc]Tc-FGFR2-2, [99mTc]Tc-FGFR2-3, and [99mTc]Tc-FGFR2-4) with different amino acid linkers between the targeted peptide moiety and the 99mTc chelating group were designed and synthesized. The in vitro cellular inhibition, internalization, and efflux results demonstrated that the four 99mTc complexes exhibited FGFR2-specific binding and prolonged cellular retention in DU145 human prostate cancer cells, which indicated that modification from the glycine side (N-terminal) of CH02 was feasible. Among them, [99mTc]Tc-FGFR2-1 exhibited the highest in vitro cellular uptake and in vivo tumor uptake at 30 min postinjection, and tumor uptake could be significantly inhibited by the competitor CH02 (53% inhibited, p < 0.05), suggesting the tumor-specific targeting ability of [99mTc]Tc-FGFR2-1. The DU145-xenografted tumor lesions were clearly visualized by single photon emission computed tomography (SPECT)/CT at 30 min postinjection of [99mTc]Tc-FGFR2-1, highlighting its potential as a SPECT imaging probe for tumor FGFR2 detection.


Assuntos
Melanoma , Peptídeos , Masculino , Humanos , Peptídeos/química , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Melanoma/metabolismo , Quelantes , Ligação Proteica , Linhagem Celular Tumoral , Microambiente Tumoral , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo
2.
Acta Pharmacol Sin ; 45(6): 1224-1236, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38467717

RESUMO

The root of Aconitum carmichaelii Debx. (Fuzi) is an herbal medicine used in China that exerts significant efficacy in rescuing patients from severe diseases. A key toxic compound in Fuzi, aconitine (AC), could trigger unpredictable cardiotoxicities with high-individualization, thus hinders safe application of Fuzi. In this study we investigated the individual differences of AC-induced cardiotoxicities, the biomarkers and underlying mechanisms. Diversity Outbred (DO) mice were used as a genetically heterogeneous model for mimicking individualization clinically. The mice were orally administered AC (0.3, 0.6, 0.9 mg· kg-1 ·d-1) for 7 d. We found that AC-triggered cardiotoxicities in DO mice shared similar characteristics to those observed in clinic patients. Most importantly, significant individual differences were found in DO mice (variation coefficients: 34.08%-53.17%). RNA-sequencing in AC-tolerant and AC-sensitive mice revealed that hemoglobin subunit beta (HBB), a toxic-responsive protein in blood with 89% homology to human, was specifically enriched in AC-sensitive mice. Moreover, we found that HBB overexpression could significantly exacerbate AC-induced cardiotoxicity while HBB knockdown markedly attenuated cell death of cardiomyocytes. We revealed that AC could trigger hemolysis, and specifically bind to HBB in cell-free hemoglobin (cf-Hb), which could excessively promote NO scavenge and decrease cardioprotective S-nitrosylation. Meanwhile, AC bound to HBB enhanced the binding of HBB to ABHD5 and AMPK, which correspondingly decreased HDAC-NT generation and led to cardiomyocytes death. This study not only demonstrates HBB achievement a novel target of AC in blood, but provides the first clue for HBB as a novel biomarker in determining the individual differences of Fuzi-triggered cardiotoxicity.


Assuntos
Proteínas Quinases Ativadas por AMP , Aconitina , Cardiotoxicidade , Histona Desacetilases , Animais , Camundongos , Cardiotoxicidade/metabolismo , Cardiotoxicidade/etiologia , Histona Desacetilases/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Masculino , Humanos , Aconitum/química , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Medicamentos de Ervas Chinesas/farmacologia
3.
Neurol Sci ; 45(6): 2845-2851, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38228940

RESUMO

AIM: The aim of this study was to determine the usefulness of magnetic resonance imaging (MRI) characteristics in discriminating H3 K27M-mutant gliomas from wildtype gliomas in the spinal cord. MATERIALS AND METHODS: Fifty-eight patients with spinal cord gliomas were enrolled in this study. The H3 K27 gene status was identified by Sanger sequencing or immunohistochemistry test of resection tumor specimens. The MR imaging characteristics were evaluated and compared between H3 K27M-mutant and wildtype gliomas using the χ2 test and the Mann-Whitney U test. RESULTS: Of 58 recruited patients, 23 (39.7%) were diagnosed with H3 K27M-mutant glioma. The H3 K27M-mutant gliomas were found to more likely occur in men compared with wildtype gliomas (87.0% vs. 42.9%, p = 0.001). On T2-weighted MR images, the signal-to-noise ratio (SNR) of H3 K27M-mutant gliomas was significantly lower than that of wildtype gliomas (103.9 ± 72.0 vs. 168.9 ± 86.8, p < 0.001). Of 35 wildtype tumors, 60% showed well-defined margin but this feature was not found in all mutant tumors (p < 0.001). The SNR of tumors on contrast-enhanced T1-weighted images of the H3 K27M-mutant gliomas was significantly lower than that of wildtype gliomas (187.7 ± 160.4 vs. 295.1 ± 207.8, p = 0.006). Receiver operating-characteristic analysis revealed that area under curve (AUC) of combination of 1/SNR on T2-weighted images, 1/SNR on contrast-enhanced T1-weighted images, ill-defined margin, and sex reached 0.937 (95% CI, 0.873-1.000) in discriminating H3 K27M-mutant gliomas. CONCLUSIONS: The MR imaging characteristics are valuable in discriminating H3 K27M-mutant from wildtype gliomas in the spinal cord and the combination of these imaging features with sex had a high strength in this discrimination.


Assuntos
Glioma , Histonas , Imageamento por Ressonância Magnética , Mutação , Neoplasias da Medula Espinal , Humanos , Masculino , Glioma/genética , Glioma/diagnóstico por imagem , Glioma/patologia , Feminino , Imageamento por Ressonância Magnética/métodos , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/patologia , Adulto , Pessoa de Meia-Idade , Histonas/genética , Adulto Jovem , Idoso , Adolescente , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia
4.
Molecules ; 29(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38998960

RESUMO

The United Nations proposed the Sustainable Development Goals with the aim to make human settlements in cities resilient and sustainable. The excessive discharge of urban waste including sludge and garden waste can pollute groundwater and lead to the emission of greenhouse gases (e.g., CH4). The proper recycling of urban waste is essential for responsible consumption and production, reducing environmental pollution and addressing climate change issues. This study aimed to prepare biochar with high adsorption amounts of iodine using urban sludge and peach wood from garden waste. The study was conducted to examine the variations in the mass ratio between urban sludge and peach wood (2/1, 1/1, and 1/2) as well as pyrolysis temperatures (300 °C, 500 °C, and 700 °C) on the carbon yield and adsorption capacities of biochar. Scanning electron microscopy, Brunauer-Emmett-Teller analysis, Fourier transform infrared spectrometry, powder X-ray diffraction, and elemental analysis were used to characterize the biochar produced at different pyrolysis temperatures and mass ratios. The results indicate that the carbon yield of biochar was found to be the highest (>60%) at a pyrolysis temperature of 300 °C across different pyrolysis temperatures. The absorbed amounts of iodine in the aqueous solution ranged from 86 to 223 mg g-1 at a mass ratio of 1:1 between urban sludge and peach wood, which were comparably higher than those observed in other mass ratios. This study advances water treatment by offering a cost-effective method by using biochar derived from the processing of urban sludge and garden waste.


Assuntos
Carvão Vegetal , Iodo , Pirólise , Esgotos , Carvão Vegetal/química , Iodo/química , Esgotos/química , Adsorção , Temperatura , Jardins , Espectroscopia de Infravermelho com Transformada de Fourier , Cidades
5.
Surg Endosc ; 37(9): 7376-7384, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37580576

RESUMO

BACKGROUND: In recent years, computer-assisted intervention and robot-assisted surgery are receiving increasing attention. The need for real-time identification and tracking of surgical tools and tool tips is constantly demanding. A series of researches focusing on surgical tool tracking and identification have been performed. However, the size of dataset, the sensitivity/precision, and the response time of these studies were limited. In this work, we developed and utilized an automated method based on Convolutional Neural Network (CNN) and You Only Look Once (YOLO) v3 algorithm to locate and identify surgical tools and tool tips covering five different surgical scenarios. MATERIALS AND METHODS: An algorithm of object detection was applied to identify and locate the surgical tools and tool tips. DarkNet-19 was used as Backbone Network and YOLOv3 was modified and applied for the detection. We included a series of 181 endoscopy videos covering 5 different surgical scenarios: pancreatic surgery, thyroid surgery, colon surgery, gastric surgery, and external scenes. A total amount of 25,333 images containing 94,463 targets were collected. Training and test sets were divided in a proportion of 2.5:1. The data sets were openly stored at the Kaggle database. RESULTS: Under an Intersection over Union threshold of 0.5, the overall sensitivity and precision rate of the model were 93.02% and 89.61% for tool recognition and 87.05% and 83.57% for tool tip recognition, respectively. The model demonstrated the highest tool and tool tip recognition sensitivity and precision rate under external scenes. Among the four different internal surgical scenes, the network had better performances in pancreatic and colon surgeries and poorer performances in gastric and thyroid surgeries. CONCLUSION: We developed a surgical tool and tool tip recognition model based on CNN and YOLOv3. Validation of our model demonstrated satisfactory precision, accuracy, and robustness across different surgical scenes.


Assuntos
Redes Neurais de Computação , Procedimentos Cirúrgicos Robóticos , Humanos , Algoritmos , Endoscopia , Bases de Dados Factuais
6.
Environ Toxicol ; 38(7): 1494-1508, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37017410

RESUMO

Silicosis is a life-threatening lung fibrotic disease caused by excessive inhalation of environmental exposure to crystalline silica-containing dust, whereas achieving therapeutic cures are constrained. Antioxidation and anti-inflammation are currently recognized as effective strategies to counteract organ fibrosis. Using naturally occurring phytomedicines quercetin (Qu) has emerged in antagonizing fibrotic disorders involving oxidative stress and inflammation, but unfortunately the hydrophilicity deficiency. Herein, chitosan-assisted encapsulation of Qu in nanoparticles (Qu/CS-NPs) was first fabricated for silicosis-associated fibrosis treatment by pulmonary delivery. Qu/CS-NPs with spherical diameters of ~160 nm, demonstrated a high Qu encapsulated capability, excellent hydrophilic stability, fantastic oxidation radical scavenging action, and outstanding controlled as well as slow release Qu action. A silicosis rat model induced by intratracheal instillation silica was established to estimate the anti-fibrosis effect of Qu/CS-NPs. After intratracheal administration, CS-NPs markedly enhanced Qu anti-fibrotic therapy efficacy, accompanying the evident changes in reducing ROS and MDA production to mitigate oxidative stress, inhibiting IL-1ß and TNF-α release, improving lung histological architecture, down-regulating α-SAM levels and suppressing ECM deposition, and thereby ameliorating silica-induced pulmonary fibrosis. Results manifested that the augmented antioxidant and anti-inflammatory activities of Qu by CS-NPs delivery was a result of achieving this remarkable improvement in curative effects. Combined with negligible systemic toxicity, nano-decorated Qu may provide a feasible therapeutic option for silicosis therapy.


Assuntos
Fibrose Pulmonar , Silicose , Ratos , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/prevenção & controle , Dióxido de Silício/toxicidade , Quercetina/farmacologia , Quercetina/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Silicose/tratamento farmacológico , Silicose/patologia , Estresse Oxidativo , Fibrose , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico
7.
Acta Pharmacol Sin ; 43(7): 1843-1856, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34845369

RESUMO

Ras has long been viewed as a promising target for cancer therapy. Farnesylthiosalicylic acid (FTS), as the only Ras inhibitor has ever entered phase II clinical trials, has yielded disappointing results due to its strong hydrophobicity, poor tumor-targeting capacity, and low therapeutic efficiency. Thus, enhancing hydrophilicity and tumor-targeting capacity of FTS for improving its therapeutic efficacy is of great significance. In this study we conjugated FTS with a cancer-targeting small molecule dye IR783 and characterized the anticancer properties of the conjugate FTS-IR783. We showed that IR783 conjugation greatly improved the hydrophilicity, tumor-targeting and therapeutic potential of FTS. After a single oral administration in Balb/c mice, the relative bioavailability of FTS-IR783 was increased by 90.7% compared with FTS. We demonstrated that organic anion transporting polypeptide (OATP) and endocytosis synergistically drove the uptake of the FTS-IR783 conjugate in breast cancer MDA-MB-231 cells, resulting in superior tumor-targeting ability of the conjugate both in vitro and in vivo. We further revealed that FTS-IR783 conjugate could bind with and directly activate AMPK rather than affecting Ras, and subsequently regulate the TSC2/mTOR signaling pathway, thus achieving 2-10-fold increased anti-cancer therapeutic efficacy against 6 human breast cancer cell lines compared to FTS both in vivo and in vitro. Overall, our data highlights a promising approach for the modification of the anti-tumor drug FTS using IR783 and makes it possible to return FTS back to the clinic with a better efficacy.


Assuntos
Antineoplásicos , Neoplasias da Mama , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Farneseno Álcool/análogos & derivados , Farneseno Álcool/farmacologia , Farneseno Álcool/uso terapêutico , Feminino , Humanos , Camundongos , Salicilatos , Proteínas ras/metabolismo , Proteínas ras/uso terapêutico
8.
Biochem Genet ; 60(5): 1781-1792, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35092560

RESUMO

Although previous studies showed that long non-coding RNAs (lncRNAs) have critical roles in the pathogenesis of acute myocardial infarction (AMI), the underlying molecular mechanism that lncRNAs participate in MI remains unclear. Herein, we explored the expression of lncRNA HOX antisense non-coding RNA (HOTAIR) in the serum of MI patients and mouse model of AMI. Biological functions of HOTAIR in hypoxic H9c2 cells, the in vitro model of MI, were also assessed. RT-qPCR results showed that HOTAIR expression was downregulated in the serum of AMI patients and AMI mice. HOTAIR overexpression promoted H9c2 cell viability and inhibited cell apoptosis under hypoxic conditions. Mechanically, HOTAIR was regulated by miR-206 and FN1 was the direct target of miR-206. More importantly, miR-206 overexpression or FN1 knockdown reversed the effect of HOTAIR overexpression on H9c2 cell viability and apoptosis under hypoxic conditions. Therefore, targeting the HOTAIR/miR-206/FN1 axis may be a promising therapeutic method for MI.


Assuntos
MicroRNAs , Infarto do Miocárdio , RNA Longo não Codificante , Animais , Apoptose/genética , Linhagem Celular , Sobrevivência Celular/genética , Fibronectinas/genética , Humanos , Camundongos , MicroRNAs/genética , Infarto do Miocárdio/genética , RNA Longo não Codificante/genética , Ratos
9.
Cancer Immunol Immunother ; 70(6): 1619-1634, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33237349

RESUMO

The microRNA let-7d has been reported to be a tumor suppressor in renal cell carcinoma (RCC). Tumor-associated macrophages (TAM) are M2-polarized macrophages that can enhance tumor growth and angiogenesis in many human cancers. However, the role of let-7d in TAM-associated RCC progression remains elusive. First, we observed a strongly inverse correlation between let-7d expression and microvessel density in RCC tissues. Furthermore, the proliferation, migration, and tube formation of HUVECs were significantly inhibited by conditioned medium from a coculture system of the phorbol myristate acetate pretreated human THP-1 macrophages and let-7d-overexpressing RCC cells. Moreover, the proportion of M2 macrophages was significantly lower in the group that was cocultured with let-7d-overexpressing RCC cells. Subcutaneous xenografts formed by the injection of let-7d-overexpressing RCC cells together with THP-1 cells resulted in a significant decrease in the M2 macrophage ratio and microvessel density compared with those formed by the injection of control RCC cells with THP-1 cells. In silico and experimental analysis revealed interleukin-10 (IL-10) and IL-13 as let-7d target genes. Importantly, the addition of IL-10 and IL-13 counteracted the inhibitory effects of the conditioned medium from the coculture system with let-7d-overexpressing RCC cells in vitro. Additionally, overexpression of IL-10 and IL-13 reversed the effects of let-7d on macrophage M2 polarization and tumor angiogenesis in vivo. Finally, the expression of IL-10 and IL-13 were inversely correlated with the expression of let-7d in RCC clinical specimens. These results suggest that let-7d may inhibit intratumoral macrophage M2 polarization and subsequent tumor angiogenesis by targeting IL-10 and IL-13.


Assuntos
Carcinoma de Células Renais/prevenção & controle , Interleucina-10/antagonistas & inibidores , Interleucina-13/antagonistas & inibidores , Neoplasias Renais/prevenção & controle , Ativação de Macrófagos/imunologia , MicroRNAs/genética , Neovascularização Patológica/terapia , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/patologia , Prognóstico , Células THP-1/imunologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Analyst ; 146(20): 6228-6238, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34528034

RESUMO

We have developed a sensitive and rapid gold nanoparticle-based immunochromatographic strip (GNP-ICS) for the detection of phenacetin (PNCT) and paracetamol (PAP) using an anti-PNCT monoclonal antibody (mAb). The sensitive anti-PNCT mAb (2D6) had a half maximal inhibitory concentration (IC50) and limit of detection (LOD) of 3.51 and 0.21 ng mL-1, respectively. Additionally, its cross-reactivity with PAP was approximately 10.1%. The developed GNP-ICS assay based on GNP-labeled mAb was sensitive for the detection of PNCT with vLOD and cut-off values of 2.5 and 50 ng mL-1 respectively and a vLOD value of 25 ng mL-1 for PAP. Furthermore, the developed icELISA and GNP-ICS assays were applied to determine PNCT-spiked beverage samples without pretreatment, in addition to a kind of PAP-containing drug. The recoveries were validated using high performance liquid chromatography (HPLC). The results revealed that the developed GNP-ICS assay was reliable for the detection of PNCT in practical samples.


Assuntos
Ouro , Nanopartículas Metálicas , Acetaminofen , Cromatografia de Afinidade , Ensaio de Imunoadsorção Enzimática , Limite de Detecção , Fenacetina
11.
Analyst ; 146(12): 3871-3879, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34028472

RESUMO

This report describes the development of a sensitive and broadly specific indirect competitive enzyme-linked immunosorbent assay (icELISA) and a gold nanoparticle-based immunochromatographic strip (GNP-ICS) assay for the detection of benzo[a]pyrene (B[a]P), using an anti-B[a]P monoclonal antibody (mAb). A broad-specific anti-B[a]P mAb (4E8) was raised from two types of haptens, with half maximal inhibitory concentrations and limits of detection (LOD) values of 2.51 and 0.54 ng mL-1, respectively. In addition, the cross-reactivity was up to 390% with structurally related compounds. The GNP-ICS assay based on a GNP-labeled mAb showed broad specificity in the detection of B[a]P and its analogues, with cut-off and visual LOD values of 100 and 10 ng mL-1, respectively. Furthermore, the recoveries from the developed icELISA and GNP-ICS assay in edible oil samples spiked with B[a]P were validated by high-performance liquid chromatography-fluorescence detection. The results revealed that the icELISA could reliably detect B[a]P in edible oils.


Assuntos
Ouro , Nanopartículas Metálicas , Anticorpos Monoclonais , Benzo(a)pireno , Ensaio de Imunoadsorção Enzimática , Óleos de Plantas
12.
Ann Hepatol ; 23: 100297, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33346094

RESUMO

INTRODUCTION AND OBJECTIVES: CASC9 and miR-424-5p are closely related with hepatocellular carcinoma (HCC) progression. This study aimed to evaluate the effect of CASC9 involved with miR-424-5p on the development of HCC. MATERIALS AND METHODS: qRT-PCR was performed to determine the mRNA expressions of CASC9 and miR-424-5p in HCC tissues/cells and adjacent normal tissues/human hepatic epithelial cells, and to analyze the relationship of CASC9 with the clinico-pathological characteristics and prognosis of HCC patients. Then, cell proliferation was measured by CCK-8 and1 clone formation assays. Apoptosis of HCC cells was measured by flow cytometry. Besides, cell migration and invasion were determined by scratch wound-healing and Transwell assays, respectively. DIANA-LncBase V2 and dual luciferase reporter gene assay were used to verify the targeted relationship between CASC9 and miR-424-5p. Bcl-2, Bax and cleaved caspase-3 expressions were detected by Western blot. RESULTS: Higher expression of CASC9 was observed in HCC tissues/ cells than in adjacent normal tissues/ human hepatic epithelial cells, and was closely linked to poor prognosis of HCC, tumor size, TNM stage, differentiation degree, lymph node metastasis and alpha-fetoprotein (AFP). Down-regulation of CASC9 decreased the proliferation, invasion and migration of HCC cells while enhancing apoptosis. Besides, CASC9 was negatively correlated with miR-424-5p. MiR-424-5p inhibitor enhanced cell proliferation, invasion and migration while decreasing apoptosis. Interestingly, siRNA-CASC9 partially offset the effects of miR-424-5p inhibitor on HCC cells. CONCLUSION: CASC9 promoted proliferation, invasion and migration and inhibited apoptosis in HCC cells by inhibiting miR-424-5p.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Apoptose , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Feminino , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , RNA Longo não Codificante/metabolismo
13.
Neuropathology ; 41(3): 183-190, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33599007

RESUMO

We investigated the risk factors for diffuse midline gliomas of the spinal cord (DMGSCs). Seventy patients with spinal cord gliomas in two hospitals were analyzed retrospectively. Sixty-nine patients that underwent surgery achieved partial or gross total removal. The patients were subdivided into some groups, based on age, WHO grade, tumor location within the cord, tumor size, and molecular profile: immunohistochemical expression of p53 and ATRX, and mutational status of Histone 3 (H3), and BRAF. Thirty-three patients had an H3 K27M mutation (47%). Some clinical characteristics were significantly different between H3 K27M mutant and H3 wild-type tumors. The main risk factors for DMGSCs were male sex, glioblastomas, and ≤ 2 spinal cord segments. The median survival period of patients with H3 K27M mutant tumors was significantly shorter than those with H3 wild-type tumors (17.0 ± 3.7 months vs censored, P < 0.0001). In the DMGSC subgroup, patients with thoracic cord tumors had a significantly better prognosis than those with cervical cord tumors (31.0 ± 6.0 vs 10.0 ± 4.8 months). Patients > 45 years of age survived significantly longer than patients < 19 years (P = 0.001). In conclusion, H3 K27M mutation significantly predicts a worse outcome of spinal cord gliomas. Anatomical location and age are the main risk factors for DMGSCs.


Assuntos
Glioma/genética , Glioma/patologia , Histonas/genética , Mutação , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA
14.
Am J Physiol Renal Physiol ; 319(2): F202-F214, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32628541

RESUMO

Kidney stone disease is a crystal concretion formed in the kidneys that has been associated with an increased risk of chronic kidney disease. MicroRNAs are functionally involved in kidney injury. Data mining using a microRNA array database suggested that miR-21 may be associated with calcium oxalate monohydrate (COM)-induced renal tubular cell injury. Here, we confirmed that COM exposure significantly upregulated miR-21 expression, inhibited proliferation, promoted apoptosis, and caused lipid accumulation in an immortalized renal tubular cell line (HK-2). Moreover, inhibition of miR-21 enhanced proliferation and decreased apoptosis and lipid accumulation in HK-2 cells upon COM exposure. In a glyoxylate-induced mouse model of renal calcium oxalate deposition, increased miR-21 expression, lipid accumulation, and kidney injury were also observed. In silico analysis and subsequent experimental validation confirmed the peroxisome proliferator-activated receptor (PPAR)-α gene (PPARA) a key gene in fatty acid oxidation, as a direct miR-21 target. Suppression of miR-21 by miRNA antagomiR or activation of PPAR-α by its selective agonist fenofibrate significantly reduced renal lipid accumulation and protected against renal injury in vivo. In addition, miR-21 was significantly increased in urine samples from patients with calcium oxalate renal stones compared with healthy volunteers. In situ hybridization of biopsy samples from patients with nephrocalcinosis revealed that miR-21 was also significantly upregulated compared with normal kidney tissues from patients with renal cell carcinoma who underwent radical nephrectomy. These results suggested that miR-21 promoted calcium oxalate-induced renal tubular cell injury by targeting PPARA, indicating that miR-21 could be a potential therapeutic target and biomarker for nephrolithiasis.


Assuntos
Oxalato de Cálcio/farmacologia , Rim/lesões , MicroRNAs/farmacologia , PPAR alfa/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Apoptose/genética , Biomarcadores/metabolismo , Oxalato de Cálcio/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Rim/metabolismo , Cálculos Renais/patologia , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , MicroRNAs/genética , Nefrocalcinose/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Biomacromolecules ; 21(6): 2176-2186, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32286801

RESUMO

Many biological high-performance composites, such as bone, antler, and crustacean cuticles, are composed of densely mineralized and ordered nanofiber materials. The mimicry of even simplistic bioinspired structures, i.e., of densely and homogeneously mineralized nanofibrillar materials with controllable mechanical performance, continues to be a grand challenge. Here, using alkaline phosphatase as an enzymatic catalyst, we demonstrate the dense, homogeneous, and spatially controlled mineralization of calcium phosphate nanostructures within networks of anionically charged cellulose nanofibrils (CNFs) and cationically charged chitin nanofibrils (ChNFs)-both emerging biobased nanoscale building blocks for sustainable high-performance materials design. Our study reveals that anionic CNFs lead to a more homogeneous nanoscale mineralization with very high mineral contents up to ca. 70 wt % with a transition from amorphous to crystalline deposits, while cationic ChNFs yield rod-like crystalline morphologies. The bone-inspired CNF bulk films exhibit a significantly increased stiffness, maintain good flexibility and translucency, and have a significant gain in wet state mechanical properties. The mechanical properties can be tuned both by the enzyme concentration and the mineralization time. Moreover, we also show a spatial control of the mineralization using kinetically controlled substrate uptake in a dialysis reactor, and by spatially selectively incorporating the enzyme into 2D printed filament patterns. The strategy highlights possibilities for spatial encoding of enzymes in tailored structures and patterns and programmed mineralization processes, promoting the potential application of mineralized CNF biomaterials with complex gradients for bone substitutes and tissue regeneration in general.


Assuntos
Materiais Biomiméticos , Nanofibras , Biomimética , Celulose , Diálise Renal
16.
BMC Health Serv Res ; 20(1): 407, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393254

RESUMO

BACKGROUND: Community-based diabetes management is known to be an important strategy for global diabetes control. In China, community-based diabetes management care, including regular blood glucose tests and guidance on medicine use, dietary control, and physical exercise provided by primary health institutions (PHIs), as one of the key contents of the national essential public health services (EPHS), was implemented since 2009 when the new round of health system reform was initiated. This study aimed to investigate the utilization of community-based diabetes management care services, and explore the factors influencing utilization from both patients' and providers' points of view. METHODS: In total, 2520 type-2 diabetes mellitus (DM) patients registered for EPHS were selected from 63 PHIs in eight counties of Shandong province, China, using multi-stage stratified sampling. Of those, 2166 patients (response rate: 85.4%) completed face-to-face structured questionnaires on their utilization of community-based diabetes management care services. Further, 63 PHIs were surveyed on diabetes care delivery, and 444 primary healthcare providers were purposively sampled from those PHIs to measure their knowledge of diabetes management care delivery, using a self-developed questionnaire. Descriptive statistics were used to analyze the delivery and utilization of diabetes management care services. Multilevel logistic regression models were used to analyze the factors associated with patients' utilization of diabetes management services. RESULTS: All 63 PHIs reported that all the required four diabetes management services were provided through EPHS. However, only 49.6% of the patients reported they fully used these services, with no statistically significant difference between urban and rural patients. Patients who had higher knowledge of diabetes and better self-efficacy in controlling the condition, were more likely to fully utilize diabetes management care. A larger number of PHI health staff per 1000 population was associated with better utilization of care. CONCLUSION: Although community-based diabetes management services are well available to Chinese DM patients under the framework of EPHS, the actual utilization of diabetes management services among the patients was poor. The size of the PHI workforce, patients' knowledge and self-efficacy in controlling diabetes, were important predictors of utilization, and could be enhanced to improve control of diabetes.


Assuntos
Serviços de Saúde Comunitária/estatística & dados numéricos , Diabetes Mellitus Tipo 2/terapia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto , Idoso , China , Estudos Transversais , Atenção à Saúde , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , População Rural , Autoeficácia , Inquéritos e Questionários
19.
J Sci Food Agric ; 98(2): 674-680, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28671318

RESUMO

BACKGROUND: Aflatoxin B1 (AFB1 ) is a kind of toxic and carcinogenic mycotoxin. A time-resolved fluoroimmunoassay (TRFIA) was established for quantitative detection of AFB1 in feed using Eu3+ -labeled IgG as tracer. RESULTS: Monoclonal antibody (McAb) against AFB1 (9B11-D7) was prepared through immunization and cell fusion and was identified as high affinity, specificity and sensibility by enzyme-linked immunosorbent assay (ELISA). The 50% inhibition value (IC50 ) was 0.81 ng mL-1 , the limit of detection (LOD) was 0.10 ng mL-1 and detection range was 0.10-3.94 ng mL-1 . Goat anti-mouse immunoglobulin G (IgG) was modified by Eu3+ -DATT, generating Eu3+ -labeled IgG. Under optimal assay conditions, TRFIA was shown to be highly sensitive and specific in detection of AFB1 . The IC50 and LOD were 94.73 pg mL-1 and 3.55 pg mL-1 , respectively, and detection range was 3.55-1.11 × 103 pg mL-1 . Cross-reactivity with AFM1 , AFB2 , AFG1 and AFG2 was 31.26%, 37.6%, 127.46% and 35.74%, respectively, but zero with other analogues. In determination of AFB1 spiked in feed sample, TRFIA showed high accuracy and precision. The average recoveries ranged from 93.71% to 97.80%, and coefficient of variation was 1.25-3.73%. Good correlation between TRFIA and HPLC was demonstrated for determination of AFB1 in feeds, confirming the reliability of the developed method. CONCLUSION: The developed TRFIA exhibited good potential for employment in the ultrasensitive detection of AFB1 in feed and could be used to determine total aflatoxins. © 2017 Society of Chemical Industry.


Assuntos
Aflatoxina B1/química , Európio/química , Fluorimunoensaio/métodos , Imunoglobulina G/química , Radioimunoensaio/métodos , Ovalbumina/química , Sensibilidade e Especificidade , Soroalbumina Bovina/química
20.
J Sci Food Agric ; 97(7): 2223-2229, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27616272

RESUMO

BACKGROUND: Fumonisins are a kind of toxic and carcinogenic mycotoxin. A rapid immunochromatographic test strip has been developed for simultaneous detection of fumonisin B1 , B2 and B3 (FB1 , FB2 and FB3 ) in maize based on colloidal gold-labelled monoclonal antibody (McAb) against FB1 probe. RESULTS: The anti-FB1 McAb (2E11-H3) was produced through immunisation and cell fusion, and identified as high affinity, specificity and sensitivity. The cross-reaction ratios with fumonisin B2 and B3 were accordingly 385% and 72.4%, while none with other analogues. The colloid gold-labelled anti-FB1 McAb probe was successfully prepared and used for establishing the immunochromatographic strip. The test strip showed high sensitivity and specificity, the IC50 for FB1 was 58.08 ng mL-1 , LOD was 11.24 ng mL-1 , calculated from standard curve. Moreover, the test strip exhibited high cross-reactivity with FB2 and FB3 , and could be applied to the simultaneous detection of FBs (FB1 :FB2 :FB3 = 12:4:1) in maize sample with high accuracy and precision. The average recoveries of FBs in maize ranged from 90.42% to 95.29%, and CVs were 1.25-3.77%. The results of the test strip for FBs samples showed good correlation with high-performance liquid chromatography analysis. CONCLUSION: The immunochromatographic test strip could be employed in the rapid simultaneous detection of FB1 , FB2 and FB3 in maize samples on-site. © 2016 Society of Chemical Industry.


Assuntos
Cromatografia de Afinidade/métodos , Contaminação de Alimentos/análise , Fumonisinas/análise , Coloide de Ouro/química , Zea mays/química , Anticorpos Monoclonais/análise , Cromatografia de Afinidade/instrumentação
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