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1.
Sci Total Environ ; 927: 172237, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38582105

RESUMO

Dichloroacetonitrile (DCAN), an emerged nitrogenous disinfection by-product (N-DBP) in drinking water, has garnered attention owing to its strong cytotoxicity, genotoxicity, and carcinogenicity. However, there are limited studies on its potential hepatotoxicity mechanisms. Understanding hepatotoxicity is essential in order to identify and assess the potential risks posed by environmental pollutants on liver health and to safeguard public health. Here, we investigated the viability, reactive oxygen species (ROS) levels, and cell cycle profile of DCAN-exposed HepG2 cells and analyzed the mechanism of DCAN-induced hepatotoxicity using both transcriptomic and metabolomic techniques. The study revealed that there was a decrease in cell viability, increase in ROS production, and increase in the number of cells in the G2/M phase with an increase in the concentration of DCAN. Omics analyses showed that DCAN exposure increased cellular ROS levels, leading to oxidative damage in hepatocytes, which further induced DNA damage, cell cycle arrest, and cell growth impairment. Thus, DCAN has significant toxic effects on hepatocytes. Integrated analysis of transcriptomics and metabolomics offers new insights into the mechanisms of DCAN-induced hepatoxicity.


Assuntos
Acetonitrilas , Metabolômica , Transcriptoma , Humanos , Transcriptoma/efeitos dos fármacos , Células Hep G2 , Acetonitrilas/toxicidade , Poluentes Químicos da Água/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo
2.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 35(9): 919-926, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-37803950

RESUMO

Acute respiratory distress syndrome (ARDS) continues to be one of the most life-threatening conditions for patients in the intensive care unit (ICU). The 2023 European Society of Intensive Care Medicine guidelines on ARDS: definition, phenotyping and respiratory support strategies (2023 Guideline) update the 2017 An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guideline: mechanical ventilation in adult patients with ARDS (2017 Guideline), including 7 aspects of 3 topics of definitions, phenotyping, and respiratory support strategies [including high flow nasal cannula oxygen (HFNO), non-invasive ventilation (NIV), neuromuscular blocking agents (NMBA), extracorporeal life support (ECLS), positive end-expiratory pressure (PEEP) with recruitment maneuvers (RM), tidal volume (VT), and prone positioning]. 2023 Guideline review and summarize the literature since the publication of the 2017 Guideline, covering ARDS and acute hypoxemic respiratory failure, as well as ARDS caused by novel coronavirus infection. Based on the most recent medical evidence, the 2023 Guideline provide clinicians with new ideas and approaches for nonpharmacologic respiratory support strategies for adults with ARDS. This article provides interpretation of the new concepts, the new approaches, the new recommended grading and new levels of evidence for ARDS in the 2023 Guideline.


Assuntos
COVID-19 , Ventilação não Invasiva , Síndrome do Desconforto Respiratório , Adulto , Humanos , Respiração Artificial , Respiração com Pressão Positiva , Síndrome do Desconforto Respiratório/terapia
3.
Ultrasound Med Biol ; 49(8): 1760-1767, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37137742

RESUMO

OBJECTIVE: The goal of the work described here was to construct a deep learning-based intelligent diagnostic model for ophthalmic ultrasound images to provide auxiliary analysis for the intelligent clinical diagnosis of posterior ocular segment diseases. METHODS: The InceptionV3-Xception fusion model was established by using two pre-trained network models-InceptionV3 and Xception-in series to achieve multilevel feature extraction and fusion, and a classifier more suitable for the multiclassification recognition task of ophthalmic ultrasound images was designed to classify 3402 ophthalmic ultrasound images. The accuracy, macro-average precision, macro-average sensitivity, macro-average F1 value, subject working feature curves and area under the curve were used as model evaluation metrics, and the credibility of the model was assessed by testing the decision basis of the model using a gradient-weighted class activation mapping method. RESULTS: The accuracy, precision, sensitivity and area under the subject working feature curve of the InceptionV3-Xception fusion model on the test set reached 0.9673, 0.9521, 0.9528 and 0.9988, respectively. The model decision basis was consistent with the clinical diagnosis basis of the ophthalmologist, which proves that the model has good reliability. CONCLUSION: The deep learning-based ophthalmic ultrasound image intelligent diagnosis model can accurately screen and identify five posterior ocular segment diseases, which is beneficial to the intelligent development of ophthalmic clinical diagnosis.


Assuntos
Aprendizado Profundo , Reprodutibilidade dos Testes , Benchmarking , Neuroimagem , Ultrassonografia
4.
Med Sci Monit ; 28: e938807, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36575635

RESUMO

Use of live laboratory animals is essential in the process of functional experimentation teaching. There are ethical problems, such as poor experimental environment, non-standard operation, and neglect of animal rights in experimental teaching. As an important basic course in life science education, functional experimentation should establish the correct ethics of use of laboratory animals. The welfare of laboratory animals has become one of the frontier directions of medical ethics research. The "4R" principle of animal welfare is based on the principles of reduction, replacement, refinement, and responsibility, which may provide a way to solve ethical problems in the teaching and research activities of functional experimentation. In addition to receiving relevant knowledge and education, laboratory animal practitioners and students in functional experimentation teaching should consciously abide by relevant regulations and rules and actively follow the "4R" principles. Animal ethics education is reflected in all teaching and research activities. Based on the principle of "4R" and the premise of guaranteeing teaching objectives, virtual simulation experiment teaching is a great supplement to functional experimentation. In teaching, medical ethics education should be strengthened to cultivate the consciousness of respecting the life of experimental animals, and awareness of laboratory animal ethics should be improved among teachers and students of functional experimentation to further promote ideological and political education in colleges and universities. This brief summary analyzes the general situation of animal ethics in functional experimentation in China based on the principle of "4R" and provides certain references and support for course teaching and training.


Assuntos
Experimentação Animal , Animais , Humanos , Bem-Estar do Animal , Direitos dos Animais , Animais de Laboratório , Estudantes
5.
Cell Rep ; 37(5): 109926, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34731629

RESUMO

Interferon regulatory factor 3 (IRF3) is an essential transductor for initiation of many immune responses. Here, we show that lncRNA-ISIR directly binds IRF3 to promote its phosphorylation, dimerization, and nuclear translocation, along with enhanced target gene productions. In vivo lncRNA-ISIR deficiency results in reduced IFN production, uncontrolled viral replication, and increased mortality. The human homolog, AK131315, also binds IRF3 and promotes its activation. More important, AK131315 expression is positively correlated with type I interferon (IFN-I) level and severity in patients with lupus. Mechanistically, in resting cells, IRF3 is bound to suppressor protein Flightless-1 (Fli-1), which keeps its inactive state. Upon infection, IFN-I-induced lncRNA-ISIR binds IRF3 at DNA-binding domain in cytoplasm and removes Fli-1's association from IRF3, consequently facilitating IRF3 activation. Our results demonstrate that IFN-I-inducible lncRNA-ISIR feedback strengthens IRF3 activation by removing suppressive Fli-1 in immune responses, revealing a method of lncRNA-mediated modulation of transcription factor (TF) activation.


Assuntos
Fator Regulador 3 de Interferon/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Macrófagos Peritoneais/metabolismo , RNA Longo não Codificante/metabolismo , Estomatite Vesicular/metabolismo , Animais , Estudos de Casos e Controles , Chlorocebus aethiops , Modelos Animais de Doenças , Inativação Gênica , Células HEK293 , Humanos , Fator Regulador 3 de Interferon/genética , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/virologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Proto-Oncogênica c-fli-1/genética , Proteína Proto-Oncogênica c-fli-1/metabolismo , Células RAW 264.7 , RNA Longo não Codificante/genética , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/metabolismo , Células Vero , Estomatite Vesicular/genética , Estomatite Vesicular/imunologia , Estomatite Vesicular/virologia , Vírus da Estomatite Vesicular Indiana/imunologia , Vírus da Estomatite Vesicular Indiana/patogenicidade
6.
Sci Rep ; 11(1): 18064, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508140

RESUMO

Membranous nephropathy (MN) and minimal change disease (MCD) are two common causes leading to nephrotic syndrome (NS). They have similar clinical features but different treatment strategies and prognoses. M-type phospholipase A2 receptor (PLA2R) is considered as a specific marker of membranous nephropathy. However, its sensitivity is only about 70%. Therefore, there is a lack of effective and noninvasive tools to distinguish PLA2R-negative MN and MCD patients without renal biopsy. A total 949 patients who were pathologically diagnosed as idiopathic MN or MCD were enrolled in this study, including 805 idiopathic MN and 144 MCD. Based on the basic information and laboratory examination of 200 PLA2R-negative MN and 144 MCD, we used a univariate and multivariate logistic regression to select the relevant variables and develop a discrimination model. A novel model including age, albumin, urea, high density lipoprotein, C3 levels and red blood cell count was established for PLA2R-negative MN and MCD. The discrimination model has great differential capability (with an AUC of 0.904 in training group and an AUC of 0.886 in test group) and calibration capability. When testing in all 949 patients, our model also showed good discrimination ability for all idiopathic MN and MCD.


Assuntos
Biomarcadores , Análise Discriminante , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/etiologia , Nefrose Lipoide/diagnóstico , Nefrose Lipoide/etiologia , Receptores da Fosfolipase A2/metabolismo , Adulto , Biópsia , Diagnóstico Diferencial , Feminino , Glomerulonefrite Membranosa/epidemiologia , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Nefrose Lipoide/epidemiologia , Vigilância da População , Prognóstico , Curva ROC , Receptores da Fosfolipase A2/genética , Estudos Retrospectivos
7.
Am J Transl Res ; 13(4): 3674-3681, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017550

RESUMO

OBJECTIVE: Care models of Healthcare Failure Mode and Effect Analysis (FMEA) were evaluated for the prevention of multi-drug resistant organisms (MDRO) infections in oral and maxillofacial surgery. METHODS: Two hundred patients who received oral and maxillofacial surgery from January to December 2017 were enrolled as the control group, and another 200 patients who received oral and maxillofacial surgery from January to December 2018 were enrolled as the FMEA group. The incidence of MDRO, the implementation of preventive and control measures, the mastery of preventive and control knowledge, and oral self-care ability were compared between the two groups. Risk Priority Number (RPN) and behavioral changes of health care personnel were observed in FMEA group. RESULTS: The FMEA group had a lower incidence of MDRO (2.00%) than the control group (6.00%) and a higher rate of acquisition of prevention and control knowledge (93.00%) than the control group (84.50%) (P < 0.05). Patients in FMEA group were higher than those in the control group in terms of compliance towards isolation signs and precautions, appropriate use of PPE, implementation of disinfection measures, hand hygiene and exercise of self-care agency (ESCA) scale scores (P < 0.05). The total RPN score of the FMEA group before and after management was 1384 and 180, respectively, and the reduction rate of total RPN scores was 86.99%. Scores with regard to knowledge, attitude, and behavior of health care personnel were increased after FMEA treatment (P < 0.05). CONCLUSION: The nursing model of FMEA for oral and maxillofacial surgery can prevent MDRO infections, reduce RPN, improve the implementation of preventive and control measures as well as oral self-care ability and the acquisition of knowledge.

8.
Immunity ; 53(6): 1168-1181.e7, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33326766

RESUMO

Viruses have evolved multiple strategies to evade elimination by the immune system. Here we examined the contribution of host long noncoding RNAs (lncRNAs) in viral immune evasion. By functional screening of lncRNAs whose expression decreased upon viral infection of macrophages, we identified a lncRNA (lncRNA-GM, Gene Symbol: AK189470.1) that promoted type I interferon (IFN-I) production and inhibited viral replication. Deficiency of lncRNA-GM in mice increased susceptibility to viral infection and impaired IFN-I production. Mechanistically, lncRNA-GM bound to glutathione S-transferase M1 (GSTM1) and blocked GSTM1 interaction with the kinase TBK1, reducing GSTM1-mediated S-glutathionylation of TBK1. Decreased S-glutathionylation enhanced TBK1 activity and downstream production of antiviral mediators. Viral infection reprogrammed intracellular glutathione metabolism and furthermore, an oxidized glutathione mimetic could inhibit TBK1 activity and promote viral replication. Our findings reveal regulation of TBK1 by S-glutathionylation and provide insight into the viral mediated metabolic changes that impact innate immunity and viral evasion.


Assuntos
Glutationa/metabolismo , Evasão da Resposta Imune , Processamento de Proteína Pós-Traducional , Proteínas Serina-Treonina Quinases/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Glutationa Transferase/metabolismo , Humanos , Imunidade Inata , Fator Regulador 3 de Interferon/metabolismo , Interferon Tipo I/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , RNA Longo não Codificante/genética , Transdução de Sinais , Viroses/genética , Viroses/imunologia , Viroses/metabolismo , Replicação Viral
9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-821010

RESUMO

@# 长链非编码RNA(lncRNA)是一类长度大于200 nt、且不编码的RNA。lncRNA已被证明与人类疾病紧密相关,尤其 是肿瘤发生发展。研究表明,肿瘤中一些异常表达的lncRNA可以通过不同的信号通路, 如Wnt/β-catenin信号通路,促进肿瘤进 展过程。在不同肿瘤组织中具有特异性表达特征的lncRNA与Wnt/β-catenin信号通路之间的相互作用显示出其作为新的生物标 志物和治疗靶点的潜能。本文就Wnt/β-catenin信号通路相关lncRNA通过调控Wnt/β-catenin信号转导,影响不同肿瘤类型发生 发展的作用进行综述。本文结果或可为临床肿瘤诊断和治疗提供新的思路。

10.
Mater Sci Eng C Mater Biol Appl ; 70(Pt 2): 969-975, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27772728

RESUMO

Inorganic/organic hybrid scaffolds have great potential for tissue engineering applications due to controllable mechanical properties and tailorable biodegradation. Here, silica/chitosan hybrid scaffolds were fabricated through the sol-gel method with a freeze drying process. 3-Glycidoxypropyl trimethoxysilane (GPTMS) and tetraethylorthosilicate (TEOS) were used as the covalent inorganic/organic coupling agent and the separate inorganic source, respectively. Hybrid scaffolds with various inorganic/organic weight ratios (I/Os) and molar ratios of chitosan and GPTMS (GCs) were examined and compared in this study. FTIR showed that higher GPTMS content resulted in the increased covalent cross-linking of the chitosan and the silica network in hybrids. Compression testing indicated that increasing the GPTMS content greatly improved the compressive strength of scaffold. LIVE/DEAD assay showed that enhanced cytocompatibility was obtained as the silica content increased. Therefore, the results confirmed that the two parameters I/O and GC can largely influence the scaffold performance, which can be used to tailor the hybrid properties.


Assuntos
Quitosana/química , Compostos Orgânicos/química , Dióxido de Silício/química , Alicerces Teciduais/química , Absorção Fisico-Química , Morte Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Força Compressiva , Humanos , Porosidade , Silanos/química , Silício/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Estresse Mecânico
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