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Triphenyl phosphate (TPHP) is a widely used organophosphate flame retardant and has biological toxicity. Previous studies showed TPHP can restrain testosterone biosynthesis in Leydig cells, while the underlying mechanisms remain unclear. In this study, C57BL/6J male mice were exposed to 0, 5, 50, and 200 mg/kg B.W. of TPHP for 30 d by oral, as well as TM3 cells were treated with 0, 50, 100, and 200 µM of TPHP for 24 h. Results showed that TPHP induced testes damage, including spermatogenesis disorders and testosterone synthesis inhibition. Meanwhile, TPHP can cause apoptosis in testicular Leydig cells and TM3 cells, as evidenced by the increased apoptosis rate and decreased Bcl-2/Bax ratio. Moreover, TPHP disrupted mitochondrial ultrastructure of testicular Leydig cells and TM3 cells, reduced healthy mitochondria content and depressed mitochondrial membrane potential of TM3 cells, as well as inhibited mitochondrial fusion proteins mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and optic atrophy 1 (Opa1) expression, without effect on mitochondrial fission proteins dynamin-related protein 1 (Drp1) and fission 1 (Fis1) in testicular tissue and/or TM3 cells. Then, the mitochondrial fusion promoter M1 was used to pre-treat TPHP-exposed TM3 cells to determine the roles of mitochondrial fusion inhibition in TPHP-induced Leydig cells apoptosis. The results showed M1 pretreatment alleviated the above changes and further mitigated TM3 cells apoptosis and testosterone levels decreased, indicating TPHP induced TM3 cells apoptosis by inhibited mitochondrial fusion. Intriguingly, the intervention experiment of N-acetylcysteine (NAC) showed that TPHP-induced mitochondrial fusion inhibition is ROS dependent, because inhibition of ROS overproduction alleviated mitochondrial fusion inhibition, and subsequently relieved TPHP-induced apoptosis in TM3 cells. In summary, above data revealed that apoptosis is a specific mechanism for TPHP-induced male reproductive toxicity, and that ROS-mediated mitochondrial fusion inhibition is responsible for Leydig cells apoptosis caused by TPHP.
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Células Intersticiais do Testículo , Dinâmica Mitocondrial , Camundongos , Animais , Masculino , Células Intersticiais do Testículo/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BL , Apoptose , Proteínas Mitocondriais/metabolismo , Organofosfatos/metabolismo , Testosterona/metabolismoRESUMO
With the abuse of antibiotics, bacterial antibiotic resistance is becoming a major public healthcare issue. Natural plants, especially traditional Chinese herbal medicines, which have antibacterial activity, are important sources for discovering potential bacteriostatic agents. This study aimed to develop a fast and reliable method for screening out antimicrobial compounds targeting the MRSA membrane from Psoralea corylifolia Linn. seed. A UPLC-MS/MS method was applied to identify the prenylated flavonoids in major fractions from the extracts of Psoralea corylifolia Linn. seed. The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of different fractions and compounds. The morphological and ultrastructural changes of MRSA were determined by scanning electron microscopy (SEM). The membrane-targeting mechanism of the active ingredients was explored by membrane integrity assays, membrane fluidity assays, membrane potential assays, ATP, and ROS determination. We identified eight prenylated flavonoids in Psoralea corylifolia Linn. seed. The antibacterial activity and mechanism studies showed that this type of compound has a unique destructive effect on MRSA cell membranes and does not result in drug resistance. The results revealed that prenylated flavonoids in Psoralea corylifolia Linn. seeds are promising candidates for the development of novel antibiotic agents to combat MRSA-associated infections.
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Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Psoralea , Psoralea/química , Cromatografia Líquida , Espécies Reativas de Oxigênio/análise , Extratos Vegetais/química , Espectrometria de Massas em Tandem , Antibacterianos/farmacologia , Antibacterianos/análise , Sementes/química , Anti-Infecciosos/farmacologia , Flavonoides/química , Trifosfato de Adenosina/farmacologiaRESUMO
Ultrasonography-guided fine-needle aspiration biopsy is the common choice for diagnosis of the suspected thyroid nodule. An algorithm(s) that finds the malignant potential of a nodule preoperatively, to overcome unnecessary diagnostic methods, does not exist. The objective of the study was to correlate thyroid nodule sizes measured by ultrasonography and risk of malignancy assessed by cytologic and histologic examinations. Data regarding fine-needle aspiration cytology and the results of histologic examinations of surgical specimens of 260 nodules were collected and analyzed. The macro or multiple calcifications, the complex echo pattern, and posterior region homogeneity were considered suspicious in ultrasonography. Bethesda system for classification of thyroid nodules was used for cytopathology. Histopathology performed as per the 2004 World Health Organization classification system. The benefit score analysis was performed for determination of clinical usefulness. Twenty-eight of 49 malignant nodules and 46 of 68 malignant nodules detected through ultrasound following fine-needle aspiration cytopathology and histopathology were <2 cm in size. A correlation was found for malignancy rate detected by ultrasonography-guided fine-needle aspiration cytology and those of the surgical specimen (r = 0.945, P = .015, R 2 = 0.894). Ultrasonography-guided fine-needle aspiration cytology had 0.994 sensitivities, 0.721 accuracies, and 0.08 to 0.945 diagnostic confidence for the detection of malignant nodules. Nodule size less than 2 mm (P = .011) was associated with the malignancy potential of thyroid nodules. Ultrasonography-guided fine-needle aspiration cytology had 19 (7%) results as a false negative and 1 (1%) results were false positive. Ultrasound-guided fine-needle aspiration cytopathology reported oversize of thyroid nodule than original but can predict the risk of malignancy. Level of Evidence: III.
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Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Biópsia por Agulha Fina , Feminino , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Carga Tumoral , Ultrassonografia/métodosRESUMO
GROWTH-REGULATING FACTORs (GRFs) play a pivotal role in the regulation of leaf size in plants and have been widely reported in plants. However, their specific functions in leaf size regulation in Liriodendron chinense remains unclear. Therefore, in this study, we identified GRF genes on a genome-wide scale in L. chinense to characterize the roles of LcGRFs in regulating leaf size. A total of nine LcGRF genes were identified, and these genes exhibited weak expression in mature leaves but strong expression in shoot apex. Notably, LcGRF2 exhibited the highest expression level in the shoot apex of L. chinense. Further RT-qPCR assay revealed that the expression level of LcGRF2 gradually decreased along with the leaf development process, and also displayed a gradient along the leaf proximo-distal and medio-lateral axes. Furthermore, overexpression of LcGRF2 in Arabidopsis thaliana resulted in increased leaf size, and significantly up-regulated the expression of genes involved in cell division like AtCYCD3;1, AtKNOLLE, and AtCYCB1;1, indicating that LcGRF2 may influence leaf size by promoting cell proliferation. This work contributes to a better understanding of the roles and molecular mechanisms of LcGRFs in the regulation of leaf size in L. chinense.
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Proteínas de Arabidopsis , Arabidopsis , Liriodendron , Liriodendron/genética , Liriodendron/metabolismo , Folhas de Planta/metabolismo , Proteínas de Arabidopsis/genética , Divisão Celular , Regulação da Expressão Gênica de PlantasRESUMO
Terpenoids are not only important component of plant floral scent, but also indispensable elements in the formation of floral color. The petals of Liriodendron chinense are rich in tetraterpene carotenoids and release large amounts of volatile monoterpene and sesquiterpene compounds during full blooming stage. However, the mechanism of terpenoid synthesis is not clear in L. chinense. In this study, we identified a LcMCT gene and characterized its potential function in carotenoids biosynthesis. A total of 2947 up-regulated differentially expressed genes (DEGs) were discerned from the transcriptomic data of L. chinense petals, with a significant enrichment of DEGs related to plant hormone signal transduction and terpenoid backbone biosynthesis. After comprehensive analysis on these DEGs, the LcMCT gene was selected for subsequent function characterization. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results showed that LcMCT was expressed at the highest level in the petals during full blooming stage, suggesting a possible role in carotenoids biosynthesis and volatile terpenoid biosynthesis. Subcellular localization showed that the LcMCT protein was localized in the chloroplast. Overexpression of LcMCT in Arabidopsis thaliana affected the expression levels of MEP pathway genes. Moreover, the MCT enzyme activity and carotenoids contents in transgenic A. thaliana were increased by 69.27% and 15.57%, respectively. These results suggest that LcMCT promotes the biosynthesis of terpenoid precursors via the MEP pathway. Our work lays a foundation for exploring the mechanism of terpenoid synthesis in L. chinense.
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Carotenoides , Liriodendron , Liriodendron/genética , Liriodendron/metabolismo , Terpenos/metabolismo , Transcriptoma , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de PlantasRESUMO
The plant-specific SQUAMOSA promoter-binding protein-like (SPL) transcription factors play a pivotal role in various developmental processes, including leaf morphogenesis and vegetative to reproductive phase transition. Liriodendron chinense and Liriodendron tulipifera are widely used in landscaping due to their tulip-like flowers and peculiar leaves. However, the SPL gene family in Liriodendron has not been identified and systematically characterized. We systematically identified and characterized the SPL family members in Liriodendron, including phylogeny, gene structure and syntenic analyses. Subsequently, we quantified the expression patterns of LcSPLs across various tissue sites through transcription-quantitative polymerase chain reaction (RT-qPCR) assays and identified the target gene, LcSPL2. Finally, we characterized the functions of LcSPL2 via ectopic transformation. Altogether, 17 LcSPL and 18 LtSPL genes were genome-widely identified in L. chinense and L. tulipifera, respectively. All the 35 SPLs were grouped into 9 clades. Both species had three SPL gene pairs arising from segmental duplication events, and the LcSPLs displayed high collinearity with the L. tulipifera genome. RT-qPCR assays showed that SPL genes were differentially expressed in different tissues, especially. Because LcSPL2 is highly expressed in pistils and leaves, it was selected to describe the SPL gene family of L. chinense by ectopic expression. We showed that overexpression of LcSPL2 in Arabidopsis thaliana resulted in earlier flowering and fewer rosette leaves. Moreover, we observed that overexpression of LcSPL2 in A. thaliana up-regulated the expression levels of four genes related to flower development. This study identified SPL genes in Liriodendron and characterized the function of LcSPL2 in advancing flower development.
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INTRODUCTION: The continuous emergence and rapid spread of multidrug-resistant bacteria have accelerated the demand for the discovery of alternative antibiotics. Natural plants contain a variety of antibacterial components, which is an important source for the discovery of antimicrobial agents. OBJECTIVE: To explore the antimicrobial activities and related mechanisms of two lavandulylated flavonoids, sophoraflavanone G and kurarinone in Sophora flavescens against methicillin-resistant Staphylococcus aureus. METHODS: The effects of sophoraflavanone G and kurarinone on methicillin-resistant Staphylococcus aureus were comprehensively investigated by a combination of proteomics and metabolomics studies. Bacterial morphology was observed by scanning electron microscopy. Membrane fluidity, membrane potential, and membrane integrity were determined using the fluorescent probes Laurdan, DiSC3(5), and propidium iodide, respectively. Adenosine triphosphate and reactive oxygen species levels were determined using the adenosine triphosphate kit and reactive oxygen species kit, respectively. The affinity activity of sophoraflavanone G to the cell membrane was determined by isothermal titration calorimetry assays. RESULTS: Sophoraflavanone G and kurarinone showed significant antibacterial activity and anti-multidrug resistance properties. Mechanistic studies mainly showed that they could target the bacterial membrane and cause the destruction of the membrane integrity and biosynthesis. They could inhibit cell wall synthesis, induce hydrolysis and prevent bacteria from synthesizing biofilms. In addition, they can interfere with the energy metabolism of methicillin-resistant Staphylococcus aureus and disrupt the normal physiological activities of the bacteria. In vivo studies have shown that they can significantly improve wound infection and promote wound healing. CONCLUSION: Kurarinone and sophoraflavanone G showed promising antimicrobial properties against methicillin-resistant Staphylococcus aureus, suggesting that they may be potential candidates for the development of new antibiotic agents against multidrug-resistant bacteria.
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Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Sophora , Sophora/química , Espécies Reativas de Oxigênio , Flavonoides/farmacologia , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Trifosfato de Adenosina/farmacologiaRESUMO
Triphenyl phosphate (TPHP) is an organophosphorus flame retardant, but its cardiac toxicity has not been adequately investigated. Therefore, in the current study, the effect of TPHP on the heart and the underlying mechanism involved was evaluated. C57BL/6 J mice were administered TPHP (0, 5, and 50 mg/kg/day) for 30 days. In addition, H9c2 cells were treated with three various concentrations (0, 50, and 150 µM) of TPHP, with and without the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine or the mitochondrial fusion promoter M1. TPHP caused cardiac fibrosis and increased the levels of CK-MB and LDH in the serum. TPHP increased the levels of ROS, malondialdehyde (MDA), and decreased the level of superoxide dismutase (SOD) and Glutathione peroxidase (GSH-Px). Furthermore, TPHP caused mitochondrial damage, and induced fusion and fission disorders that contributed to mitophagy in both the heart of C57BL/6 J mice and H9c2 cells. Transcriptome analysis showed that TPHP induced up- or down-regulated expression of various genes in myocardial tissue and revealed enriched apoptosis pathways. It was also found that TPHP could remarkably increase the expression levels of Bax, cleaved Caspase-9, cleaved Caspase-3, and decreased Bcl-2, thereby causing apoptosis in H9c2 cells. Taken together, the results suggested that TPHP promoted mitophagy through mitochondria fusion dysfunction resulting from oxidative stress, leading to fibrosis by inducing myocardial apoptosis.
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Retardadores de Chama , Miócitos Cardíacos , Organofosfatos , Camundongos , Animais , Cardiotoxicidade/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Retardadores de Chama/metabolismo , Mitofagia , Camundongos Endogâmicos C57BL , Compostos Organofosforados/metabolismo , Estresse Oxidativo , Apoptose , FibroseRESUMO
Lamivudine, adefovir, telbivudine, and entecavir are nucleoside analogues that can inhibit hepatitis B virus replication and are licensed in China by the Food and Drug Administration. This study presents the cases of 2 patients who were chronically infected with HBV and suffered hepatic failure resulting from withdrawal of telbivudine and adefovir, respectively.
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Adenina/análogos & derivados , Antivirais/uso terapêutico , Hepatite B Crônica/patologia , Lamivudina/uso terapêutico , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/virologia , Organofosfonatos/uso terapêutico , Adenina/efeitos adversos , Adenina/uso terapêutico , Adulto , Antivirais/efeitos adversos , Guanina/efeitos adversos , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Histocitoquímica , Humanos , Lamivudina/efeitos adversos , Falência Hepática Aguda/patologia , Transplante de Fígado , Masculino , Adesão à Medicação , Necrose , Organofosfonatos/efeitos adversos , Telbivudina , Timidina/efeitos adversos , Timidina/análogos & derivados , Timidina/uso terapêuticoRESUMO
INTRODUCTION: Fine needle aspiration cytology is preferred for thyroid nodules preoperatively, but has disadvantages of false-negative and false-positive results. OBJECTIVE: To compare the diagnostic performance of grayscale ultrasound, subjective color Doppler ultrasound, and combined features of grayscale ultrasound and subjective color Doppler ultrasound in predicting thyroid carcinoma, using results of the fine needle aspiration cytology as the reference standard. METHODS: Data from gray-scale ultrasound images, subjective color Doppler ultrasound images, and the fine needle aspiration cytology of 325 nodules of 250 patients (age ≥ 18 years) were collected and analyzed. Hypo-echogenicity than adjacent strap muscle, micro-lobulated or irregular margins, micro- or mixed calcifications, and taller-than-wide shapes were considered as a suspicious malignant nodule in grayscale ultrasound. Marked vascularity was considered as a suspicious malignant nodule in color Doppler ultrasound. The Bethesda system for classification of thyroid nodules was used for cytopathology. RESULTS: With respect to the results of fine-needle aspiration cytology for detecting suspicious malignant nodules, for grayscale ultrasound, subjective color Doppler ultrasound, and combined gray-scale with subjective color Doppler ultrasound, sensitivities were 0.564, 0.600 and 0.691, respectively and accuracies were 0.926, 0.919 and 0.959, respectively. Suspicious malignant nodules detectability for grayscale ultrasound, subjective color Doppler ultrasound, and combined gray-scale with subjective color Doppler ultrasound were 0.09-0.56 diagnostic confidence, 0.08-0.61 diagnostic confidence, and 0.063-0.7 diagnostic confidence, respectively. CONCLUSIONS: The combined gray-scale with subjective color Doppler ultrasound-guided fine-needle aspiration biopsies are recommended for the diagnosis of thyroid carcinoma. LEVEL OF EVIDENCE: III.
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Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Adolescente , Biópsia por Agulha Fina , Humanos , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologiaRESUMO
The endoplasmic reticulum (ER) is the largest tubular reticular organelle spanning the cell. As the main site of protein synthesis, Ca2+ homeostasis maintenance and lipid metabolism, the ER plays a variety of essential roles in eukaryotic cells, with ER molecular chaperones participate in all these processes. In recent years, it has been reported that the abnormal expression of ER chaperones often leads to a variety of neurodevelopmental disorders (NDDs), including abnormal neuronal migration, neuronal morphogenesis, and synaptic function. Neuronal development is a complex and precisely regulated process. Currently, the mechanism by which neural development is regulated at the ER level remains under investigation. Therefore, in this work, we reviewed the recent advances in the roles of ER chaperones in neural development and developmental disorders caused by the deficiency of these molecular chaperones.
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There are many films and televisions (FATs) on the Internet, but the quality is uneven. This study explores the ability of college students to screen good films and resist bad films in television works in such a large environment. In the deep learning model of FAT, the ability of college students to think about the ideas expressed and the degree of influence on college students' values are analyzed. Based on this conceptual basis, a questionnaire is designed for the intention and influencing factors of college students' FAT innovation and entrepreneurship. It reflects the influence of concentration on FAT learning, the cognitive level of deep learning, the ability to process deep learning ideas, the feeling of the teaching process, and the process of self-learning, which all positively impact college students' FAT entrepreneurial intentions. The importance of innovative deep learning is highlighted, which proves that a good deep learning course guidance method can improve students' interest and ability and provide a reference for relevant colleges and universities to cultivate pertinent talents of the field of FAT.
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Busulfan, a chemotherapeutic agent for cancer, has detrimental effects on germ cells and fertility, yet the specific mechanisms remain largely uncertain. The blood-testis barrier (BTB) maintains a suitable microenvironment for germ cells self-renewal and spermatogenesis by blocking the interference and damage of deleterious substances. Therefore, we hypothesized that BTB abnormalities might be involved in busulfan-induced oligospermia. To verify the hypothesis, thirty male Balb/c mice were randomly administered with busulfan (at a total dose of 40 mg/kg body weight) by intraperitoneal injection for 4 weeks to establish the model of oligospermia. The results displayed that busulfan caused testicular histopathological lesions and spermatogenesis disorder. Meanwhile, busulfan disrupted BTB integrity and lessened the expressions of BTB junction proteins, including Occludin, Claudin-11 and Connexin-43. Furthermore, busulfan activated the endoplasmic reticulum (ER) stress and PERK-eIF2α signaling pathway, reflected by the increased protein expressions of GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. Finally, to evaluate whether the ER stress is involved in busulfan-induced BTB destruction, the ER stress inhibitor 4-Phenylbutyric acid (4-PBA, 1 mM) was used to intervene in busulfan-exposed TM4 cells. The results displayed that inhibition of ER stress alleviated the reduction of BTB junction protein expressions induced by busulfan in TM4 cells. These data collectively indicated that busulfan-induced BTB impairment was mediated by triggering ER stress and activation of the PERK-eIF2α signaling pathway, thereby damaging the spermatogenesis, providing a new therapeutic target for male infertility induced by busulfan.
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Fator de Iniciação 2 em Eucariotos , Oligospermia , Fator 4 Ativador da Transcrição/metabolismo , Animais , Apoptose , Barreira Hematotesticular/metabolismo , Bussulfano/toxicidade , Estresse do Retículo Endoplasmático , Fator de Iniciação 2 em Eucariotos/metabolismo , Humanos , Masculino , Camundongos , Transdução de Sinais , eIF-2 Quinase/metabolismoRESUMO
Bile acids are commonly known as one of the vital metabolites derived from cholesterol. The role of bile acids in glycolipid metabolism and their mechanisms in liver and cholestatic diseases have been well studied. In addition, bile acids also serve as ligands of signal molecules such as FXR, TGR5, and S1PR2 to regulate some physiological processes in vivo. Recent studies have found that bile acids signaling may also play a critical role in the central nervous system. Evidence showed that some bile acids have exhibited neuroprotective effects in experimental animal models and clinical trials of many cognitive dysfunction-related diseases. Besides, alterations in bile acid metabolisms well as the expression of different bile acid receptors have been discovered as possible biomarkers for prognosis tools in multiple cognitive dysfunction-related diseases. This review summarizes biosynthesis and regulation of bile acids, receptor classification and characteristics, receptor agonists and signaling transduction, and recent findings in cognitive dysfunction-related diseases.
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Ácidos e Sais Biliares , Disfunção Cognitiva , Animais , Ácidos e Sais Biliares/metabolismo , Disfunção Cognitiva/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Transdução de Sinais/fisiologiaRESUMO
BACKGROUND: The aim of this study is to evaluate the effects of treprostinil injection on the control of pulmonary blood pressure in children with congenital heart disease (CHD) complicated by severe pulmonary arterial hypertension (PAH). METHODS: Eighty children with CHD complicated by severe pulmonary arterial hypertension admitted to our hospital from January 2015 to June 2018 were selected and randomly divided into a control group (N.=40) and a treatment group (N.=40). Based on standard treatment, the treatment group was intravenously infused with 8-12 ng/kg·min treprostinil, while the control group received the same dose of normal saline. Hemodynamic parameters such as BP, AP, P and SpO
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Anti-Hipertensivos , Epoprostenol/análogos & derivados , Cardiopatias Congênitas , Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Anti-Hipertensivos/uso terapêutico , Criança , Epoprostenol/uso terapêutico , Hipertensão Pulmonar Primária Familiar , Cardiopatias Congênitas/cirurgia , HumanosRESUMO
OBJECTIVE: To investigate the correlation of carotid intima-media thickness (IMT) with endothelial function and atherosclerosis degree in patients with type 2 diabetes mellitus. METHODS: A total of 80 patients with type 2 diabetes mellitus admitted and treated in our hospital from January 2017 to January 2018 were selected and randomly divided into two groups (nâ=â40). Patients who were definitely diagnosed with type 2 diabetes mellitus were selected as observation group, and individuals who received health examination and were excluded from type 2 diabetes mellitus were enrolled as control group. The diagnosed proportions of carotid plaque, Crouse scores, endothelial-dependent flow-mediated vasodilation (FMD) function and nitroglycerin-mediated dilation (NMD) function of the brachial arteries in the two groups were compared. The indexes related to vascular endothelial functions [vascular endothelial growth factor (VEGF), endothelin-1 (ET-1) and nitric oxide (NO) levels] in the two groups were detected. The correlations of Crouse score with brachial arterial FMD value, VEGF level, ET-1 level and NO level in observation group were analyzed. RESULTS: The diagnosed proportion of carotid plaque in observation group was significantly higher than that in control group (Pâ<â0.05), and the Crouse score in observation group was higher than that in control group (Pâ<â0.05). The brachial arterial FMD value in observation group was remarkably lower than that in control group (Pâ<â0.05). Compared with control group, VEGF and ET-1 levels were significantly reduced in observation group (Pâ<â0.05), with the statistical increase of NO level (Pâ<â0.05). In observation group, the Crouse score was negatively correlated with the brachial arterial FMD value, VEGF level and ET-1 level, whereas positively correlated with the NO level (Pâ<â0.05). CONCLUSION: Our data show that the carotid IMT is increased significantly among patients with type 2 diabetes mellitus, and the vascular endothelial function is impaired. Moreover, after the occurrence of atherosclerosis, we found the carotid IMT is negatively correlated with endothelial-dependent FMD, as well as levels of VEGF and ET-1, whereas shows positive correlation with the vasodilative factor NO.
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Aterosclerose/fisiopatologia , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea/instrumentação , Diabetes Mellitus Tipo 2/fisiopatologia , Endotélio Vascular/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Abstract Introduction: Fine needle aspiration cytology is preferred for thyroid nodules preoperatively, but has disadvantages of false-negative and false-positive results. Objective: To compare the diagnostic performance of grayscale ultrasound, subjective color Doppler ultrasound, and combined features of grayscale ultrasound and subjective color Doppler ultrasound in predicting thyroid carcinoma, using results of the fine needle aspiration cytology as the reference standard. Methods: Data from gray-scale ultrasound images, subjective color Doppler ultrasound images, and the fine needle aspiration cytology of 325 nodules of 250 patients (age ≥ 18 years) were collected and analyzed. Hypo-echogenicity than adjacent strap muscle, micro-lobulated or irregular margins, micro- or mixed calcifications, and taller-than-wide shapes were considered as a suspicious malignant nodule in grayscale ultrasound. Marked vascularity was considered as a suspicious malignant nodule in color Doppler ultrasound. The Bethesda system for classification of thyroid nodules was used for cytopathology. Results: With respect to the results of fine-needle aspiration cytology for detecting suspicious malignant nodules, for grayscale ultrasound, subjective color Doppler ultrasound, and combined gray-scale with subjective color Doppler ultrasound, sensitivities were 0.564, 0.600 and 0.691, respectively and accuracies were 0.926, 0.919 and 0.959, respectively. Suspicious malignant nodules detectability for grayscale ultrasound, subjective color Doppler ultrasound, and combined gray-scale with subjective color Doppler ultrasound were 0.09-0.56 diagnostic confidence, 0.08-0.61 diagnostic confidence, and 0.063-0.7 diagnostic confidence, respectively. Conclusion: The combined gray-scale with subjective color Doppler ultrasound-guided fine-needle aspiration biopsies are recommended for the diagnosis of thyroid carcinoma. Level of Evidence: III.
Resumo Introdução: A citologia da punção aspirativa com agulha fina é preferida para nódulos tireoidianos no pré-operatório, mas apresenta desvantagens de resultados falso-negativos e falso-positivos. Objetivo: Comparar o desempenho diagnóstico da ultrassonografia em escala de cinza, do doppler colorido subjetivo e da combinação dos recursos da ultrassonografia em escala de cinza e do doppler colorido subjetivo na previsão do carcinoma da tireoide com os resultados da citologia da punção aspirativa com agulha fina como padrão de referência. Método: Dados de imagens de ultrassonografia em escala de cinza, imagens subjetivas da ultrassonografia com doppler colorido e citologia da punção aspirativa com agulha fina de 325 nódulos de 250 pacientes (idade ≥ 18 anos) foram coletados e analisados. A hipoecogenicidade da musculatura adjacente, as margens microlobuladas ou irregulares, as microcalcificações ou calcificações mistas e os formatos mais altos do que largos foram considerados como um nódulo maligno suspeito na ultrassonografia em escala de cinza. A vascularização acentuada foi considerada um nódulo maligno suspeito na ultrassonografia com doppler colorido. O sistema Bethesda para classificação de nódulos tireoidianos foi usado para a citopatologia. Resultados: Com relação aos resultados da citologia por punção aspirativa com agulha fina para detecção de nódulos malignos suspeitos, as sensibilidades foram de 0,564, 0,600 e 0,691 para a ultrassonografia em escala de cinza, ultrassonografia com doppler colorido subjetivo e escala de cinza combinada com ultrassonografia com doppler colorido subjetivo, respectivamente, e as acurácias foram 0,926, 0,919 e 0,959, respectivamente. A detectabilidade de nódulos suspeitos malignos para ultrassonografia em escala de cinza, ultrassonografia com doppler colorido subjetivo e escala de cinza combinada com ultrassonografia com doppler colorido subjetivo foram de 0,09-0,56, 0,08-0,61 e 0,063-0,7 de confiança diagnóstica, respectivamente. Conclusões: A ultrassonografia em escala de cinza combinada com o doppler colorido subjetivo e biópsias por punção aspirativa com agulha fina guiadas por ultrassonografia são recomendados para o diagnóstico de carcinoma da tireoide. Nível de evidência: III.
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Humanos , Adolescente , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Estudos Retrospectivos , Sensibilidade e Especificidade , Biópsia por Agulha FinaRESUMO
Presently, there have been a lot of documents confirmed that aflatoxin B1 could promote the incident rate of hepato-cellular carcinoma, but the specific mechanism is not completely clear. Some evidences showed that it might relate to oxidative stress and inflammatory reaction. So the rat hepato-cellular carcinoma model was applied in this study for being discussed. Aflatoxin B1 was applied for inducing the rats to produce hepato-cellular carcinoma model to evaluate the expression of histopathology and glutathione transferase. At the same time, we also detected the expression of antioxidase, pro-inflammatory cytokine, proliferating cell nuclear antigen and etc in rat hepato-cellular carcinoma tissues. The histo-pathological results showed that the necrosis of liver cells could be observed after being induced by Aflatoxin B1 for 4 weeks. We could observe obvious hepato-cellular carcinoma in 10th week. The level of reactive oxygen species in liver cancer rose obviously, and the activity of antioxidant enzymes reduced. At the same time, the expression level of pro-inflammatory cytokine, TNFα, IL-1α, proliferating cell nuclear antigen and etc all increased significantly. In conclusion, the histological characteristics of hepato-cellular carcinoma could be induced by aflatoxin B1, and the progression of hepato-cellular carcinoma related closely to inflammatory reaction.
RESUMO
Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is an essential process for virus infection, such as HIV and hepatitis C, and plays a role in immune escape. However, the role of DC-SIGN in hepatitis B virus (HBV) infection is still unknown. The aim of this study was to investigate the role of DC-SIGN in mediating the maturation and activation of dendritic cells (DCs) when infected by HBV. Highly mannosylated HBV particles were obtained by treating HBV-producing HepG2.2.15 cells with the a-mannosidase I-inhibitor kifunensine. Highly mannosylated HBV or wild type HBV was added to infect the DCs of the DC-SIGN gene-silencing group and normal group, respectively. Then, the expression of CDla, CD80, CD83, CD86 and HLA-DR on DCs was detected by flow cytometry, the capacity of stimulating lymphocyte proliferation was tested by MTT assay, the level of IL-12p70 that was released by DCs was measured by enzyme-linked immunosorbent assay, and the expression of the proteins NF-κBp65 and p38 was detected by western blot. Both wild type and highly mannosylated HBV could promote DCs maturation and activation. However, the highly mannosylated HBV could promote DCs immune activation more strongly. The difference in the effect on DCs between the two types of HBV could be eliminated by DC-SIGN gene silencing. DC-SIGN can promote the maturation and activation of DCs when recognized HBV, but wild type HBV can escape recognition by DC-SIGN to a certain extent with the help of demannosylated modification, leading to defective DCs function and chronic HBV infection.
Assuntos
Moléculas de Adesão Celular/metabolismo , Células Dendríticas/imunologia , Vírus da Hepatite B/imunologia , Lectinas Tipo C/metabolismo , Receptores de Superfície Celular/metabolismo , Antígenos CD/análise , Western Blotting , Proliferação de Células , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Antígenos HLA-DR/análise , Células Hep G2 , Hepatócitos/virologia , Humanos , Interleucina-12/metabolismo , Linfócitos/imunologia , Fator de Transcrição RelA/análise , Proteínas Quinases p38 Ativadas por Mitógeno/análiseRESUMO
The pathogenesis of acute liver failure has not been fully elucidated. The present study investigated the effects of the serum from patients with hepatitis E virus (HEV)-related acute liver failure on human liver cell survival and apoptosis, and evaluated the protective effects of anti-lipopolysaccharide(LPS) antibody recognizing core polysaccharide against acute liver failure serum-induced apoptosis. Serum was collected from patients with HEV-related acute liver failure. The levels of endotoxin (LPS) in the serum were measured using a quantitative tachypleus amebocyte lysate endotoxin detection kit with a chromogenic endpoint. Serum with a mean concentration of LPS was incubated with L02 human liver cells and the rate of apoptosis was detected by flow cytometry. The apoptotic rate was also evaluated in liver cells incubated with antibody and the HEV-related acute liver failure serum. The results indicated that the concentration of LPS in the serum of patients with HEV-related acute liver failure was 0.26±0.02 EU/ml, which was significantly higher than that of the control group (P<0.05). The rate of apoptosis in the human liver cells induced by acute liver failure serum was 5.83±0.42%, which was significantly increased compared with that in the cells treated with the serum of healthy individuals (P<0.05). The apoptotic rate of the cells incubated with antibody and the acute liver failure serum was 5.53±0.51%, which was lower than that of the cells incubated with acute liver failure serum alone (P>0.05). These results indicate that the serum of patients with HEV-related acute liver failure induces the apoptosis of human liver cells. LPS may be directly involved in the apoptosis of human liver cells. Moreover, the presence of the antibody did not significantly reduce the level of apoptosis of liver cells exposed to HEV-related acute liver failure serum.