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Microvascular invasion of HCC is an important factor affecting postoperative recurrence and prognosis of patients. Preoperative diagnosis of MVI is greatly significant to improve the prognosis of HCC. Currently, the diagnosis of MVI is mainly based on the histopathological examination after surgery, which is difficult to meet the requirement of preoperative diagnosis. Also, the sensitivity, specificity and accuracy of MVI diagnosis based on a single imaging feature are low. In this paper, a robust, high-precision cross-modality unified framework for clinical diagnosis is proposed for the prediction of microvascular invasion of hepatocellular carcinoma. It can effectively extract, fuse and locate multi-phase MR Images and clinical data, enrich the semantic context, and comprehensively improve the prediction indicators in different hospitals. The state-of-the-art performance of the approach was validated on a dataset of HCC patients with confirmed pathological types. Moreover, CMIR provides a possible solution for related multimodality tasks in the medical field.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Hospitales , Periodo Posoperatorio , SemánticaRESUMEN
MRI is crucial for the diagnosis of HCC patients, especially when combined with CT images for MVI prediction, richer complementary information can be learned. Many studies have shown that whether hepatocellular carcinoma is accompanied by vascular invasion can be evidenced by imaging examinations such as CT or MR, so they can be used as a multimodal joint prediction to improve the prediction accuracy of MVI. However, it is high-risk, time-consuming and expensive in current clinical diagnosis due to the use of gadolinium-based contrast agent (CA) injection. If MRI could be synthesized without CA injection, there is no doubt that it would greatly optimize the diagnosis. Based on this, this paper proposes a high-quality image synthesis network, MVI-Wise GAN, that can be used to improve the prediction of microvascular invasion in HCC. It starts from the underlying imaging perspective, introduces K-space and feature-level constraints, and combines three related networks (an attention-aware generator, a convolutional neural network-based discriminator and a region-based convolutional neural network detector) Together, precise tumor region detection by synthetic tumor-specific MRI. Accurate MRI synthesis is achieved through backpropagation, the feature representation and context learning of HCC MVI are enhanced, and the performance of loss convergence is improved through residual learning. The model was tested on a dataset of 256 subjects from Run Run Shaw Hospital of Zhejiang University. Experimental results and quantitative evaluation show that MVI-Wise GAN achieves high-quality MRI synthesis with a tumor detection accuracy of 92.3%, which is helpful for the clinical diagnosis of liver tumor MVI.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Invasividad Neoplásica , Imagen por Resonancia Magnética/métodos , Medios de Contraste/farmacología , RadiofármacosRESUMEN
As the most common malignant tumor worldwide, hepatocellular carcinoma (HCC) has a high rate of death and recurrence, and microvascular invasion (MVI) is considered to be an independent risk factor affecting its early recurrence and poor survival rate. Accurate preoperative prediction of MVI is of great significance for the formulation of individualized treatment plans and long-term prognosis assessment for HCC patients. However, as the mechanism of MVI is still unclear, existing studies use deep learning methods to directly train CT or MR images, with limited predictive performance and lack of explanation. We map the pathological "7-point" baseline sampling method used to confirm the diagnosis of MVI onto MR images, propose a vision-guided attention-enhanced network to improve the prediction performance of MVI, and validate the prediction on the corresponding pathological images reliability of the results. Specifically, we design a learnable online class activation map (CAM) to guide the network to focus on high-incidence regions of MVI guided by an extended tumor mask. Further, an attention-enhanced module is proposed to force the network to learn image regions that can explain the MVI results. The generated attention maps capture long-distance dependencies and can be used as spatial priors for MVI to promote the learning of vision-guided module. The experimental results on the constructed multi-center dataset show that the proposed algorithm achieves the state-of-the-art compared to other models.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Invasividad Neoplásica/patologíaRESUMEN
Gardenia jasminoides fruits are extensively grown worldwide, with a large harvest, and its major medicinal ingredients are geniposide and crocins. Research on their accumulation and biosynthsis-related enzymes is rare. In this study, the accumulation of geniposide and crocin of G. jasminoides fruits at different developmental stages were clarified by HPLC. The highest cumulative amount of geniposide was 2.035% during the unripe-fruit period, and the highest content of crocin was 1.098% during the mature-fruit period. Furthermore, transcriptome sequencing was performed. A total of 50 unigenes encoding 4 key enzymes related in geniposide biosynthsis pathways were screened, and 41 unigenes encoding 7 key enzymes in the pathways of crocin were elucidated. It was found that the expression levels of differentially expressed genes of DN67890_c0_g1_i2-encoding GGPS, which is highly related to geniposide biosynthesis, and DN81253_c0_g1_i1-encoding lcyB, DN79477_c0_g1_i2-encoding lcyE, and DN84975_c1_g7_i11-encoding CCD, which are highly related to crocin biosynthesis, were consistent with the accumulation of geniposide and crocin content, respectively. The qRT-PCR results showed that the trends of relative expression were consistent with transcribed genes. This study provides insights for understanding the geniposide and crocin accumulation and biosynthsis during fruit development in G. jasminoides.
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Schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) are common neuropsychiatric disorders that lead to neuroinflammation in the pathogenesis. It is possible to further explore the connection between inflammation in the brain and SCZ, BD, and MDD. Therefore, we systematically reviewed PubMed and Web of Science on brain inflammatory markers measured in SCZ, BD, and MDD postmortem brains. Out of 2166 studies yielded by the search, 46 studies met the inclusion criteria in SCZ, BD, and MDD postmortem brains. The results were variable across inflammatory markers. For example, 26 studies were included to measure the differential expression between SCZ and control subjects. Similarly, seven of the included studies measured the differential expression of inflammatory markers in patients with BD. The heterogeneity from the included studies is not clear at present, which may be caused by several factors, including the measured brain region, disease stage, brain source, medication, and other factors.
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Trastorno Bipolar , Trastorno Depresivo Mayor , Esquizofrenia , Humanos , Trastorno Depresivo Mayor/metabolismo , Encéfalo/metabolismo , Trastorno Bipolar/metabolismo , Esquizofrenia/metabolismo , AutopsiaRESUMEN
OBJECTIVE: Liver fibrosis is a frequently occurring liver injury which lacks of effective treatment clinically. Here, we investigated the protective effects of a novel compound Gorse isoflavone alkaloid (GIA) against liver fibrosis. METHODS: Totally forty rats were randomly divided into four groups. Then we established a model of liver fibrosis induced by the intragastric administration of carbon tetrachloride (CCl4). This treated group was followed by the intragastric administration of GIA and colchicine. Then the liver index and spleen index, and liver function indexes were detected by kit. Western blotting assay was performed to estimate the expression of Transforming Growth Factor-ß1 (TGF-ß1) and related proteins. Tissue fibrosis was observed by Masson staining. RESULTS: Our results suggested that GIA reduced the deposition of collagen fibres and the fibrosis index hydroxyproline (Hyp) of liver tissue. Furthermore, we found that GIA significantly decreased the expression of Transforming Growth Factor-ß1 (TGF-ß1) and the ratio of p-smad2/3 to smad2/3, enhanced the level of superoxide dismutase (SOD), and decreased the concentration of malonic dialdehyde (MDA) in the liver. CONCLUSIONS: Our findings revealed that GIA has a beneficial effect to resist the liver fibrosis, and could be ideal for potential use in antifibrotic drugs for the liver.
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Non-small cell lung cancer (NSCLC) is a malignant tumor with high morbidity and mortality, with a high recurrence rate after surgery, which directly affects the life and health of patients. Recently, many studies are based on Computed Tomography (CT) images. They are cheap but have low accuracy. In contrast, the use of gene expression data to predict the recurrence of NSCLC has high accuracy. However, the acquisition of gene data is expensive and invasive, and cannot meet the recurrence prediction requirement of all patients. In this paper, we proposed a low-cost, high-accuracy residual multilayer perceptrons (ResMLP) recurrence prediction method. First, several proposed ResMLP modules are applied to construct a deep regression estimation model. Then, we build a mapping function of mixed features (handcrafted features and deep features) and gene data via this model. Finally, the recurrence prediction task is realized, by utilizing the gene estimation data obtained from the regression model to learn the information representation related to recurrence. The experimental results show that the proposed method has strong generalization ability and can reach 86.38% prediction accuracy. Clinical Relevance- This study improved the preoperative recurrence of NSCLC prediction accuracy from 78.61% by the conventional method to 86.38% by our proposed method using only the CT image.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/genética , Progresión de la Enfermedad , Genotipo , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Recurrencia Local de Neoplasia/patología , Redes Neurales de la ComputaciónRESUMEN
TDO2 is a key enzyme in the kynurenine metabolic pathway, which is the most important pathway of tryptophan metabolism. It has been shown that miRNAs are involved in cell metastasis through interaction with target mRNAs. In this study, we found 645 miRNAs that could be immunoprecipitated with TDO2 through the RNA-immunoprecipitation experiment. miR-126-5p was selected as the research target, which was also confirmed by dual-luciferase reporter assay. Through qRT-PCR analysis, it was verified that the overexpression of miR-126-5p promoted the expression of TDO2, PI3K/AKT and WNT1. Meanwhile, it was verified that overexpression of miR-126-5p can promote intracellular tryptophan metabolism by HPLC. We also verified the effects of miR-126-5p on cell proliferation, migration, and invasion by cck-8, cell colony formation and trans-well assay in both HCCLM3 cells and HepG2 cells. In vivo experiments were also conducted to verify that miR-126-5p promoted tumor formation and growth via immunohistochemical detection of cell infiltration and proliferation to generate markers Ki-67, BAX, and VEGF. In conclusion, our results suggest that miR-126-5p is a biomarker and a potential new treatment target in the progression of HCC via promoting the expression of TDO2.
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Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , MicroARNs/genética , Triptófano Hidroxilasa/genética , Animales , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Ratones Endogámicos BALB C , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Triptófano/genética , Triptófano/metabolismo , Triptófano Hidroxilasa/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Due to their multipotency and ability for self-renewal, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold great promise for generating hepatocytes. Previous research has successfully generated hepatocytes from early-passage [i.e., passage (P)3] hUC-MSCs; however, the populations of early-passage cells are limited, and these cells cannot produce sufficient functional hepatocytes for large-scale application in clinical therapy. Thus, a thorough investigation of the hepatic differentiation potential of in vitro-aged hUC-MSCs is needed. METHODS: hUC-MSCs were passaged in vitro and subcultured every 3 days up to P8, and their morphology, proliferative capacity, liver-specific marker expression, and liver function at the end of each passage were analyzed. The efficiency of the hepatogenic differentiation of hUC-MSCs driven by a functional hit 1 (FH1)-based strategy at different passages was also evaluated. RESULTS: The in vitro-aged hUC-MSCs gradually displayed morphological inhomogeneity, had reduced proliferative capability, and exhibited senescent properties while maintaining adipogenic and osteogenic differentiation potential. Additionally, senescence also decreased the expression of messenger RNA (mRNA) levels in albumin (ALB) and alpha 1-antitrpsin (A1AT) in these cells and their relative protein expression, which is the marker of a mature hepatocyte. The liver function of the in vitro-aged hUC-MSCs also deteriorated gradually. Finally, the percentage of hepatocyte-like cells (HLCs) generated from in vitro-aged hUC-MSCs reduced significantly, and the mature hepatocyte functions, such as ALB secretion, glycogen synthesis, low-density lipoprotein (LDL) intake, and indocyanine green (ICG) uptake, also changed. CONCLUSIONS: hUC-MSCs possess mature hepatocytes' specific markers and functions, which change gradually as they undergo cell senescence. Due to the loss of these properties within in vitro subcultures, the hepatic differentiation efficiency of in vitro-aged hUC-MSCs decreased dramatically in the late passage (P8). The current study provides valuable information can inform future research on liver disease.
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Tryptophan metabolism plays a role in the occurrence and development of hepatocellular carcinoma cells. By degrading certain amino acids, tumor growth can be limited while maintaining the body's normal nutritional requirements. Tryptophan side-chain oxidase (TSO) enzyme can degrade tryptophan, and its inhibitory effect on hepatocellular carcinoma cells is worthy of further study. To investigate the degradation effect on tryptophan, TSO was isolated and purified from qq Pseudomonas. The reaction products were identified with high performance liquid chromatography (HPLC) and high-performance liquid chromatography tandem mass spectrometry (HPLC-MS). De novo sequencing provided the complete amino acid sequence of TSO. The results of CCK-8, colony formation, transwell, and qPCR confirmed that TSO had inhibitory effects on the proliferation and migration of HCCLM3 (human hepatocarcinoma cell line) and HepG2 cells. The results of flow cytometry confirmed its apoptotic activity. In animal experiments, we found that the tumor-suppressive effect was better in the oncotherapy group than the intraperitoneal injection group. The results of immunohistochemistry also suggested that TSO could inhibit proliferation and promote apoptosis. In conclusion, a specific enzyme that can degrade tryptophan and inhibit the growth of hepatoma cells was authenticated, and its basic information was obtained by extraction/purification and amino acid sequencing.
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Antineoplásicos/farmacología , Proteínas Bacterianas/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Oxigenasas de Función Mixta/farmacología , Triptófano/metabolismo , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Apoptosis/genética , Proteínas Bacterianas/biosíntesis , Proteínas Bacterianas/genética , Proteínas Bacterianas/aislamiento & purificación , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones , Ratones Desnudos , Oxigenasas de Función Mixta/biosíntesis , Oxigenasas de Función Mixta/genética , Oxigenasas de Función Mixta/aislamiento & purificación , Modelos Moleculares , Antígeno Nuclear de Célula en Proliferación/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Estructura Secundaria de Proteína , Pseudomonas/química , Pseudomonas/enzimología , Pseudomonas/genética , Transducción de Señal , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
BACKGROUND: Because the liver is central to the physiology of the body, primary hepatocytes are widely used in liver pathology and physiological research, such as liver drug screening, bioartificial liver support system, and cell therapy for liver diseases. However, the source of primary hepatocytes is limited. We describe a novel non-transgenic protocol that facilitates the rapid generation of hepatocyte-like cells from human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), providing a new source of functional hepatocytes. METHODS: In this study, we used hUC-MSCs and human induced pluripotent cells (iPSCs) derived mesenchymal stem cells (iMSCs) to investigate the new induction strategy. Passage 3 MSCs were induced into hepatocyte-like cells using small-molecule compounds combined with cell factors in vitro. Functional hit 1 (FH1), a promising small molecule compound was achieved to replace HGF in the hepatocyte maturation stage to induce the hepatocyte-like cells differentiation. RESULTS: We rapidly induced hUC-MSCs and human iMSCs into hepatocyte-like cells within 10 days in vitro, and the cells were morphologically similarly to both hepatocytes derived from the hepatocyte growth factor (HGF)-based method and the primary hepatocytes. They expressed mature hepatocyte special genes and achieved functions such as glycogen storage, albumin expression, urea secretion, cytochrome P450 activity, Low-density lipoprotein (LDL) uptake, and indocyanine green (ICG) uptake. CONCLUSIONS: We successfully established a small-molecule protocol without using HGF to differentiate MSCs into hepatocyte-like cells, which provides a rapid and cost-effective platform for in vitro studies of liver disease.
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BACKGROUND: Subtilisin QK is a serine protease in the subtilisin family, and is fermented by Bacillus subtilis QK02. The fibrinolytic activity of subtilisin QK was measured by detecting low molecular weight degradation products using a spectrophotometric method developed by Japan Bio Science Laboratory Co., Ltd. Subtilisin QK powder can maintain its fibrinolytic activity for more than 24 months when it is stored at room temperature and protected from light. Our previous results showed that subtlisin QK directly degraded cross-linked fibrins in the fibrin plate assay and effectively inhibited thrombosis in the mouse thrombus model. The aim of this study was to determine the acute toxicity, potential subchronic toxicity, and safety pharmacology of subtilisin QK in Sprague-Dawley (SD) rats. METHODS: In the acute toxicity study, a single oral dose of 100,000 FU/kg was administered to 10 female and 10 male SD rats. In the 28-day subchronic toxicity, 60 female and 60 male SD rats were randomly assigned to four experimental groups (daily oral dose of 0, 2500, 7500 and 25,000 FU/kg). In the safety pharmacology study, 20 female and 20 male SD rats were randomly assigned to four experimental groups (single oral dose of 0, 500, 1500 and 5000 FU/kg). RESULTS: No death occurred and no adverse effects were observed in the acute toxicity study at a dose of 100,000 FU/kg. In the 28-day subchronic toxicity study, several hematological and blood biochemical parameters showed increases or decreases; however, due to the lack of a dose-response relationship, these differences were considered unrelated to treatment. In the safety pharmacology study, no adverse effects were observed on the central nervous of SD rats post-administration up to a dose of 5000 FU/kg subtilisin QK. CONCLUSION: The results showed that oral consumption of subtilisin QK is of low toxicological concern. No adverse effects were observed at doses of 2500, 7500, and 25,000 FU/kg in the 28-day subchronic toxicity, and the no-observed-adverse-effect level (NOAEL) of subtilisin QK was 25,000 FU/kg.
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Fibrinolíticos/toxicidad , Subtilisinas/toxicidad , Administración Oral , Animales , Femenino , Fibrinolíticos/farmacología , Masculino , Ratas Sprague-Dawley , Subtilisinas/farmacología , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad SubcrónicaRESUMEN
Despite several studies suggesting the effectiveness of traditional Chinese medicine (TCM) in schizophrenia, there is still a lack of systematic summary and analysis on the role of TCM as adjuvant therapy in chronic schizophrenia. For this purpose, we conducted a meta-analysis to study the efficacy of TCM as an adjuvant combined with antipsychotics in the treatment of chronic schizophrenia. Until April 2020, based on the review of six electronic databases, eight articles were selected. The articles compared TCM decoction assisted antipsychotic therapies with an antipsychotic alone in the treatment of chronic schizophrenia by analyzing a total of 810 cases. The results showed that TCM combined with antipsychotics have beneficial effects on the Positive and Negative Syndrome Scale (PANSS), including the changes in total score, negative score, and the clinical effects evaluated by the PANSS scale. Subgroup analysis showed that the effects of auxiliary TCM with different efficacy on the positive and psychopathological scores were significantly different. It was found that adjuvant treatment with TCM can reduce some side effects and improve the patient's living conditions in the evaluation of the Schizophrenia Quality Of Life Scale (SQLS). Many studies have proved that TCM is safe and well-tolerated. Although the difficulties of using limited TCM remains to be generalized, it still has great potential in the adjuvant treatment of chronic schizophrenia.
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This study aimed to investigate the effect of dissolved humic acid (dHA) on Zn bioavailability and the subsequent influence on the Zn-induced thyroid toxicity. Zn toxicity was assessed using a yeast bioassay in the presence and absence of dHA. With increasing concentration of dHA, the toxic effects decreased, and the free Zn concentrations detected by the anodic stripping voltammetry (ASV) method also decreased. The high correlation (R = 0.92, pâ¯<â¯0.001) between toxic effects and free Zn concentrations indicated that Zn thyroid toxicity largely comes from the free Zn fraction. Water samples from the Qing River in Beijing were also assayed for thyroid toxicity. The results revealed that the metals might contribute to the toxicity. The known thyroid hormone-disrupting metals, namely, Zn, Cd and Hg, were analyzed. The cause-effect relationship between the observed thyroid toxicity and free Zn concentrations as well as their dose-effect relationships were examined. Our results showed that Zn might be the major contributor to the observed thyroid toxicity caused by metals. These results suggest that the ASV method and the identified major contributor (Zn) may be used in lieu of conventional environmental analyses to follow the progression of a risk assessment or remediation strategy.
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Sustancias Húmicas , Glándula Tiroides/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Levaduras/efectos de los fármacos , Zinc/toxicidad , Beijing , Bioensayo , Disponibilidad Biológica , Cadmio/análisis , Cadmio/toxicidad , Mercurio/análisis , Mercurio/toxicidad , Medición de Riesgo , Ríos/química , Zinc/análisisRESUMEN
OBJECTIVE: This study explored the effects of sucralfate intervention as a novel treatment for paraquat (PQ) poisoning in Sprague-Dawley (SD) rats. METHODS: After PQ poisoning, the SD rats were randomly divided into the PQ control group (treated with normal saline), the sodium bicarbonate (SB) treatment group, and the sucralfate (LTL) treatment group. Then, the rats were administered normal saline, sodium bicarbonate solution, or sucralfate suspension as an intervention by gastric lavage. At 1, 3, 6, and 10days after poisoning, the left lungs of some rats were removed to determine the lung wet/dry (W/D) weight ratio. Additionally, the serum cytokine levels were measured, and the lung and kidney tissues were pathologically examined. RESULTS: After treatment, the signs and symptoms of the rats were improved, the mortality rate was reduced, the W/D weight ratio of the lung was lower, the cytokine levels [transforming growth factor (TGF)-ß1, interleukin (IL)-10, and tumor necrosis factor (TNF)-α] were decreased, and the pathological injuries of the lungs and kidneys were improved. Moreover, sucralfate was significantly more effective than the control (normal saline) group and the SB treatment group. CONCLUSION: The results showed that early gastrointestinal lavage with sucralfate effectively reduced the inflammatory response and lung and kidney injuries and improved the survival of the SD rats.
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Antiinflamatorios/uso terapéutico , Antídotos/uso terapéutico , Herbicidas/envenenamiento , Paraquat/envenenamiento , Sucralfato/uso terapéutico , Animales , Citocinas/sangre , Lavado Gástrico , Riñón/efectos de los fármacos , Riñón/patología , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Ratas , Ratas Sprague-Dawley , Bicarbonato de Sodio/uso terapéuticoRESUMEN
A rapid recombinant human thyroid (hTR) gene yeast bioassay was used to evaluate the effect of dissolved humic acid on thyroid receptor antagonistic activity of ZnCl2.The concentration of bio-available zinc after its reaction with dissolved humic acids was measured by anodic stripping voltammetry (ASV).Furthermore,the reaction mechanism of humic acid and zinc was investigated by three-dimensional excitation-emission matrix fluorescence spectroscopy (3DEEM).The results revealed that ZnCl2 demonstrated strong thyroid receptor antagonistic activity,and the concentration inhibiting 20% of the maximum effect of ZnCl2 was 1.70×10-5 mol·L-1.The thyroid receptor antagonistic activity of ZnCl2 was reduced by 30%-50% after the reaction of dissolved humic acids.The results of ASV showed that the concentration of bio-available zinc was decreased after the reaction of dissolved humic acids,the result was similar to that of bioassay test.The thyroid receptor antagonistic activity of the mixed solution of humic acid and ZnCl2 was increased after UV radiation treatment,however it was still lower than the antagonistic activity induced by ZnCl2.The results of 3DEEM showed that ZnCl2 could reduce the fluorescence peak intensity of humic acid,which could intuitively characterize the interaction between humic acid and ZnCl2.The above results can provide basic data and theoretical support for zinc toxicity study in aquatic environment and the establishment of water quality criteria for znic.
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Cloruros/efectos adversos , Sustancias Húmicas/análisis , Receptores de Hormona Tiroidea/antagonistas & inhibidores , Contaminantes Químicos del Agua/efectos adversos , Compuestos de Zinc/efectos adversos , Bioensayo , Humanos , Espectrometría de Fluorescencia , Calidad del Agua , Levaduras , ZincRESUMEN
PURPOSE: To determine the influence of denture base resins coated with antibacterial coating on water sorption, solubility and monomer elution. METHODS: The values of water sorption and solubility were measured according to YY 0270-2003 and gas chromatography was used to examine the leachability of 4 commercially available heat-cured acrylic resins between experimental group and control group. Degree of crosslinking of the experimental heat-cured acrylic denture bases we remeasured by soxhlet extraction method. The data was analyzed by 17.0 software package. RESULTS: The values of water sorption, solubility and monomer elution of experimental group were lower compared to the control group. Degree of crosslinking of Heraeus reins was the highest among the experimental heat-cured acrylic denture bases. CONCLUSIONS: There is a same trend among water sorption, degree of crosslinking and the monomer elution. When the degree of crosslinking increases, the values of water sorption and monomer elution decrease. Antibacterial coating can improve the comprehensive properties of the denture base resins.
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Resinas Acrílicas , Bases para Dentadura , Ensayo de Materiales , Solubilidad , Antibacterianos , Calor , AguaRESUMEN
α-Mannosidosis storage disease is a rare autosomal recessive disease that is caused by a deficiency of the lysosomal enzyme α-mannosidase. In this article, a proband in China was preliminarily diagnosed as having α-mannosidosis by clinical symptoms, imaging examination, and enzyme assay. Definitive diagnosis was performed by directly sequencing the MAN2B1 gDNA and cDNA of the peripheral blood leukocyte from the patient. Finally, denaturing high-performance liquid chromatography screening, conservative analysis, and protein secondary structure prediction were used to identify the novel mutation. The results showed that the patient has compound heterozygous mutations in the MAN2B1 gene, c.856G>A (p.E286K, novel) and c.788C>T (p.P263L). Her parents are heterozygote that carry one of these two mutations respectively. Pathogenicity identification of the novel mutation showed that the p.E286K mutation is a disease-causing mutation. Our work enriches the human MAN2B1 gene mutation database. As far as we know, this research is thus far the first gene diagnosis case of a Chinese patient with α-mannosidosis.
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Mutación Missense/genética , alfa-Manosidasa/genética , alfa-Manosidosis/diagnóstico , alfa-Manosidosis/genética , Preescolar , China , Secuencia Conservada/genética , Análisis Mutacional de ADN , Enzimas/sangre , Enzimas/genética , Femenino , Humanos , Linaje , Polimorfismo de Nucleótido Simple/genética , Estructura Secundaria de ProteínaRESUMEN
Sterile alpha motif domain-containing 11 (SAMD11) is evolutionarily conserved from zebrafish to human. Mouse Samd11 is predominantly expressed in developing retinal photoreceptors and the adult pineal gland, and its transcription is directly regulated by the cone-rod homeodomain protein Crx. However, there has been little research on human SAMD11. To investigate the function of human SAMD11, we first cloned its coding sequence (CDS) and identified up to 45 novel alternative splice variants (ASVs). Mouse Samd11 ASVs were also identified by aligning the mouse Samd11 expressed sequence tags (ESTs) with the annotated sequence. However, the range of expression and transcriptional regulation of SAMD11 differs between human and mouse. Human SAMD11 was found to be widely expressed in many cell lines and ocular tissues and its transcription was not regulated by CRX, OTX2 or NR2E3 proteins. Furthermore, functional analysis indicated that human SAMD11 could promote cell proliferation slightly. In conclusion, this study elucidated the basic characteristics of human SAMD11 and revealed that, although the occurrence of alternative splicing of SAMD11 was conserved, the function of SAMD11 may vary in different species.
Asunto(s)
Empalme Alternativo , Córnea/metabolismo , Proteínas del Ojo/genética , Retina/metabolismo , Células Fotorreceptoras Retinianas Bastones/metabolismo , Animales , Línea Celular , Córnea/citología , Exones , Etiquetas de Secuencia Expresada , Proteínas del Ojo/metabolismo , Regulación de la Expresión Génica , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Intrones , Ratones , Receptores Nucleares Huérfanos/genética , Receptores Nucleares Huérfanos/metabolismo , Factores de Transcripción Otx/genética , Factores de Transcripción Otx/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Retina/citología , Células Fotorreceptoras Retinianas Bastones/citología , Especificidad de la Especie , Transactivadores/genética , Transactivadores/metabolismoRESUMEN
BACKGROUND: Mucopolysaccharidosis type IIIB (MPS IIIB) is a lysosomal storage disorder caused by over 130 mutations in NAGLU gene. However, there are not much mutations that have been reported in China. Here we studied five MPS IIIB patients from three unrelated Chinese families. METHODS: Urine test and NAGLU activity assay were used to validate the patients' type of MPS. We performed DNA analyses by direct sequencing, PCR-DHPLC, and PCR-restriction enzyme techniques. In addition, prenatal gene diagnosis was performed to one couple with two pregnancies. Finally RT-PCR and bioinformatics analysis were used to identify mutations. RESULT: A total of six different mutations were found, including a novel deletion, c.867delC, and five missense mutations, c.1081T>C (p.W361R) (novel), c.700C>T (p.R234C), c.874G>A (p.G292R), c.1693C>T (p.R565W), and c.1694G>A (p.R565Q). Prenatal diagnosis revealed that the first fetus was a compound heterozygote carrying two mutations (p.R565W and p.R565Q), whereas the second fetus carried only p.R565Q mutation. CONCLUSIONS: Our research may enrich the mutation spectrum of the NAGLU gene in the Chinese population and help us further in understanding the pathogenesis of MPS IIIB.