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1.
J Med Imaging Radiat Oncol ; 68(3): 250-256, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38563291

RESUMO

INTRODUCTION: The purpose of the study was to determine the usefulness of Ga-68 DOTATATE PET/MR in the identification of tumours in individuals with multiple endocrine neoplasia type 1 (MEN1). METHODS: In this retrospective investigation, five individuals who had tested positive for a hereditary MEN1 variant underwent Ga-68 DOTATATE PET/MR between May 2020 and January 2023. Several types of tumours associated with MEN1 were studied. MEN1-related tumours included pituitary, parathyroid, gastroenteropancreatic, and adrenal. The rates of lesion identification between MRI, Ga-68 DOTATATE PET, and Ga-68 DOTATATE PET/MRI were examined. The maximum and mean standard uptake values (SUVmax and SUVmean) were evaluated in carefully delineated volumes of interest (VOI) for the relevant tumours. RESULTS: Of the 24 primary lesions, 14 were identified by Ga-68 DOTATATE PET, 18 by MRI, and 20 by Ga-68 DOTATATE PET/MRI. Two pituitary tumours were detected by all three techniques. All parathyroid tumours that were not detected by Ga-68 DOTATATE PET and MRI were found by Tc-99m MIBI SPECT/CT or/and EUS. Ga-68 DOTATATE PET/MR detected more gastroenteropancreatic lesions. All adrenal tumours not identified by Ga-68 DOTATATE PET were found by MRI or CT. The median SUVmax for lesions identified on Ga-68 DOTATATE PET/MRI was 18.4 (range, 3.8-85.2), and the median SUVmean was 12.0 (range, 2.3-49.8). CONCLUSION: The combination of Ga-68 DOTATATE PET and MRI demonstrated a higher detection rate and may be more useful in the work-up of MEN1 providing a panoramic view of MEN1-related lesions. To increase the identification of MEN1-associated neuroendocrine lesions in the parathyroid gland, approaches other than Ga-68 DOTATATE PET/MRI should be used.


Assuntos
Imageamento por Ressonância Magnética , Neoplasia Endócrina Múltipla Tipo 1 , Compostos Organometálicos , Tomografia por Emissão de Pósitrons , Humanos , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico por imagem , Masculino , Feminino , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Adulto , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Imagem Multimodal/métodos , Idoso , Neoplasias das Paratireoides/diagnóstico por imagem , Adulto Jovem
3.
Front Plant Sci ; 14: 1307492, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38098788

RESUMO

The immature winter flush affects the flower bud differentiation, flowering and fruit of litchi, and then seriously reduces the yield of litchi. However, at present, the area estimation and growth process monitoring of winter flush still rely on manual judgment and operation, so it is impossible to accurately and effectively control flush. An efficient approach is proposed in this paper to detect the litchi flush from the unmanned aerial vehicle (UAV) remoting images of litchi crown and track winter flush growth of litchi tree. The proposed model is constructed based on U-Net network, of which the encoder is replaced by MobeilNetV3 backbone network to reduce model parameters and computation. Moreover, Convolutional Block Attention Module (CBAM) is integrated and convolutional layer is added to enhance feature extraction ability, and transfer learning is adopted to solve the problem of small data volume. As a result, the Mean Pixel Accuracy (MPA) and Mean Intersection over Union (MIoU) on the flush dataset are increased from 90.95% and 83.3% to 93.4% and 85%, respectively. Moreover, the size of the proposed model is reduced by 15% from the original model. In addition, the segmentation model is applied to the tracking of winter flushes on the canopy of litchi trees and investigating the two growth processes of litchi flushes (late-autumn shoots growing into flushes and flushes growing into mature leaves). It is revealed that the growth processes of flushes in a particular branch region can be quantitatively analysed based on the UAV images and the proposed semantic segmentation model. The results also demonstrate that a sudden drop in temperature can promote the rapid transformation of late-autumn shoots into flushes. The method proposed in this paper provide a new technique for accurate management of litchi flush and a possibility for the area estimation and growth process monitoring of winter flush, which can assist in the control operation and yield prediction of litchi orchards.

4.
Clin Nucl Med ; 48(11): 987-988, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37756486

RESUMO

ABSTRACT: A 2.6-cm solid cystic lesion in the pancreatic head was found in a 51-year-old woman on CT. A pancreatic neuroendocrine tumor was suspected, and a 68 Ga-DOTATATE PET/MRI was performed, which showed increased tracer uptake in the lesion. However, postsurgical pathologic examination indicated a pancreatic serous cystadenoma. Here, we reported a case of microcystic pancreatic serous cystadenoma that could be misdiagnosed as a pancreatic neuroendocrine tumor on a 68 Ga-DOTATATE PET/MRI.


Assuntos
Cistadenoma Seroso , Tumores Neuroendócrinos , Compostos Organometálicos , Neoplasias Pancreáticas , Feminino , Humanos , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Cistadenoma Seroso/diagnóstico por imagem , Cistadenoma Seroso/patologia , Cistadenoma Seroso/cirurgia , Neoplasias Pancreáticas/patologia , Tomografia por Emissão de Pósitrons , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
5.
Clin Nucl Med ; 48(4): 378-379, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36758557

RESUMO

ABSTRACT: Adrenocorticotropic hormone (ACTH)-secreting renal neuroendocrine tumor (NET) is extremely rare. A left renal mass was detected on ultrasound in a 26-year-old patient with ACTH-dependent Cushing syndrome. The lesion demonstrated slightly high density and moderate uptake of radiotracer on 68 Ga-DOTATATE PET/CT, suspected to be a NET. Renal vein sampling revealed excessive ACTH secretion from the left kidney. Histopathological examination after surgery finally confirmed the diagnosis of a functioning renal NET.


Assuntos
Neoplasias Renais , Tumores Neuroendócrinos , Compostos Organometálicos , Humanos , Adulto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Hormônio Adrenocorticotrópico , Tumores Neuroendócrinos/patologia , Rim/patologia
6.
J Pharm Biomed Anal ; 224: 115199, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36527856

RESUMO

Yihuang decoction (YHD) is one of the most famous formulas in tradition Chinese medicine (TCM) and has been clinically used for treatment of vaginitis, pelvic inflammation and other gynecological diseases for hundreds of years. However, its chemical composition remains unclear. In this study, high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS) was employed for its chemical profiling investigation. As a result, 90 components were chemically defined, including 23 alkaloids, 14 organic acids, 3 phenylethanoid glycosides, 4 iridoid glycosides, 5 terpenoid lactones, 10 flavonoids, 8 nucleobases and nucleosides, 12 amino acids, and 11 other compounds. In addition, 8 representative compounds (acteoside, allantoin, berberine, 4-O-feruloylquinic acid, 5-O-feruloylquinic acid, gallic acid, geniposidic acid, and phellodendrine) were simultaneously determined in 10 batches of YHD samples by HPLC with a diode array detector (HPLC-DAD). For all the analytes, their calibration curves showed good linearity (R2 >0.9990) within the test ranges. RSDs of precision, repeatability and stability test were all below 3.50%. The overall recoveries ranged from 93.63% to 105.02%, with RSDs less than 3.50%. This study is supposed to exhibit a comprehensive chemical profiling of YHD and to provide some strong basis for quality control and even for action mechanism of this ancient classical prescription.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa , Nucleosídeos
7.
Sci Rep ; 12(1): 19691, 2022 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-36385273

RESUMO

As awareness of climate-related freshwater quality problems increases, more research is needed to better understand how climate impacts water quality. Climate has significant impacts on the mixing regime and nutrient status of lakes. However, the relationship between climatic variables, mixing regime, and nutrient status in large monomictic lakes requires further study. Here we applied a three-dimensional ecosystem model to the large monomictic Lake Biwa, where hypoxia had recurred over the past 60 years. The model was validated using monitoring data, and the relationships among mixing regime, nutrient status, and climatic variables have been investigated. The turnover timing, which represented the mixing regime, varied by 36 days and depended most on wind speed but least on air temperature. In the early period prior to waste-water treatment there was a strong linear relationship between phosphorus and deep-water dissolved oxygen (DO) concentrations. Following this period, the relationship weakened but remained significant. In addition, we find a weak relationship between turnover timing and deep-water DO concentrations. We suggest that later turnover timing may favor lower deep-water DO concentrations, which in turn may favor release of legacy nutrients from sediments. Although waste-water treatment has improved conditions in the lake, climate change induced alteration of turnover timing may adversely influence water quality. Maintaining water quality under continued warming may require more rigorous controls on phosphorus loading to the lake.


Assuntos
Ecossistema , Lagos , Monitoramento Ambiental , Fósforo/análise , Nutrientes/análise
8.
Cell Death Discov ; 8(1): 423, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36266265

RESUMO

Previous studies have shown that pyruvate carboxylase (PC) plays a key role in the occurrence and progression of thyroid cancer (TC); however, the relationship between PC and iodine-refractory TC is unclear. Therefore, the present study aimed to investigate the molecular mechanism of PC in the malignant progression and loss of iodine uptake in papillary TC (PTC) and to explore the potential therapeutic effect of PC inhibitors in iodine-refractory PTC. PC increased cell proliferation, invasion, and metastasis, inhibited expression of the iodine metabolism-related genes TSHR, NIS, TPO, and TG, and decreased the iodine-uptake capacity by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway in PTC cell lines. Furthermore, the PC inhibitor ZY-444 effectively inhibited the activation of PC, reduced the malignant invasiveness, and restored the expression of iodine metabolism-related genes and the iodine-uptake capacity in PTC cells. These findings suggest that PC activation is involved in the progression of iodine-refractory TC and that PC inhibitors may represent a potentially novel targeted therapy for iodine-refractory TC.

9.
Front Oncol ; 12: 796391, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35273910

RESUMO

Accurate diagnosis and grading are critical for pancreatic neuroendocrine neoplasm (pNEN) management. This study compares the diagnostic and grading value of 68Ga-DOTATATE PET/MR and 18F-FDG PET/MR for pNENs separately as well as in combination. A total of 36 patients with histologically confirmed pNENs, who underwent both 68Ga-DOTATATE PET/MR and 18F-FDG PET/MR within 2 weeks from 2020 to 2021, were retrospectively collected and analyzed. The maximum standardized uptake values of 68Ga-DOTATATE (G-SUVmax) and 18F-FDG (F-SUVmax) on PET and the minimum values of apparent diffusion coefficient (ADCmin) on MR were measured on the lesions with known histological grading (25 by surgery, 11 by biopsy). Receiver-operating characteristic analysis was applied to determine the cutoffs of these parameters or their combinations for differentiation between G1 and G2, as well as between low-grade and high-grade pNENs. The Spearman rank correlation coefficient was used to assess the correlation between the imaging parameters and the maximum tumor diameters. The detection rate of 68Ga-DOTATATE PET imaging alone was 95%, 87.5%, and 37.5% for G1, G2, and G3, respectively. Adding 18F-FDG PET or MR sequences of PET/MR increased the detection rate to 100% in all grades. Among the three parameters, G-SUVmax had the highest diagnostic rate in predicting tumor grade. It presented a sensitivity of 87.5% and a specificity of 80.0% with a cutoff value of 42.75 for differentiating G2 from G1 pNETs and a sensitivity and specificity of 100% and 71.4% with a cutoff value of 32.75 in predicting high-grade pNENs. The ratio of G-SUVmax to F-SUVmax (G-SUVmax/F-SUVmax) showed slight improvement in the diagnostic rate, while the product of G-SUVmax and ADCmin (G-SUVmax*ADCmin) did not improve the diagnostic rate. 68Ga-DOTATATE PET/MR alone is sufficient for the diagnosis of pNENs and the prediction of various grades.

10.
Clin Nucl Med ; 47(4): 299-304, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35143455

RESUMO

PURPOSE: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with metastatic potential. Both 68Ga-DOTATATE and 18F-FDG PET/CT scans have been demonstrated to have important roles in imaging PPGLs, but less is known about the performance of PET/MRI for PPGLs. The study is aimed to investigate whether diffusion-weighted imaging-MRI (DWI-MRI) has an added value to PET imaging in the identification of PPGL lesions by means of integrated PET/MRI. METHODS: Eleven patients who underwent both 18F-FDG and 68Ga-DOTATATE PET/MRI within 2 weeks were retrospectively included in the study. A total of 56 PPGL lesions were analyzed, and lesion-based detection rates of 68Ga-DOTATATE PET, 18F-FDG PET, DWI-MRI, and PET/MRI were calculated and compared, respectively. RESULTS: 68Ga-DOTATATE PET was superior to 18F-FDG PET and DWI-MRI in imaging PPGLs with a lesion-based detection rate of 96.4% (54/56) (95% confidence interval [CI], 87.7%-99.6%), 85.7% (48/56) (95% CI, 76.3%-95.2%), and 89.3% (50/56) (95% CI, 80.9%-97.6%), respectively. PET/MRI with DWI could improve the detection rate of 68Ga-DOTATATE and 18F-FDG PET alone up to 100% in metastatic PPGLs. Lesions of PPGL demonstrated markedly higher tracer uptake in 68Ga-DOTATATE PET than in 18F-FDG PET (P = 0.009 for primary lesion, P = 0.033 for metastases). CONCLUSIONS: 68Ga-DOTATATE PET showed a higher detection rate than 18F-FDG for PPGLs. In integrated PET/MRI, MRI had an added value to 18F-FDG PET but not much to 68Ga-DOTATATAE PET in identifying PPGL lesions.


Assuntos
Neoplasias das Glândulas Suprarrenais , Compostos Organometálicos , Paraganglioma , Feocromocitoma , Fluordesoxiglucose F18 , Humanos , Imageamento por Ressonância Magnética/métodos , Paraganglioma/diagnóstico por imagem , Paraganglioma/patologia , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Cintilografia , Estudos Retrospectivos
11.
Clin Nucl Med ; 46(8): 671-674, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33661203

RESUMO

ABSTRACT: A 36-year-old asymptomatic woman was incidentally found to have a huge mass in the pancreas by ultrasound during routine health screening. The mass was suspected of neuroendocrine tumor or solid pseudopapillary tumor by subsequent abdominal CT. 18F-FDG and 68Ga-DOTATATE PET/MR were acquired for presurgical assessment of the tumor invasion and malignant potential, which revealed intense FDG uptake and mild DOTATATE uptake. The tumor was completely resected, and postsurgical pathology demonstrated pancreatoblastoma with neuroendocrine manifestations. This case showed the metabolic and biological features of pancreatoblastoma on the 18F-FDG and 68Ga-DOTATATE PET/MR.


Assuntos
Fluordesoxiglucose F18 , Imageamento por Ressonância Magnética , Imagem Multimodal , Compostos Organometálicos , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Adulto , Feminino , Humanos , Achados Incidentais
12.
Biomed Pharmacother ; 137: 111307, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33561648

RESUMO

OBJECTIVE: Dendrobium nobile is a genuine Chinese medicine. Dendrobium nobile Lindl. alkaloids (DNLA) protects against CCl4-induced acute liver injury. This study used RNA-Seq to explore the mechanisms. METHODS: Mice were pretreated with DNLA (10 and 20 mg/kg, po) for 7 days, and subsequently intoxicated with CCl4 (20 µL/kg, ip for 24 h). Liver RNA was extracted and subjected to RNA-Seq. The bioinformatics, including PCA, GO, KEGG, two-dimensional clustering, Ingenuity Pathways Analysis (IPA), and Illumina BaseSpace Correlation Engine (BSCE) were used to analyze the data. qPCR was performed on selected genes to verify RNA-Seq results. RESULTS: DNLA protection against CCl4 hepatotoxicity was confirmed by histopathology. PCA revealed the distinct gene expression patterns between the different treatment groups. GO showed that CCl4 induced the activation, adhesion and proliferation of immune cells. KEGG showed CCl4 induced oxidative stress, diseases and compromised adaptive responses. CCl4 induced differentially expressed genes (DEGs) were identified by DESeq2 with Padj < 0.05 and 2D-clustered with other groups. DNLA reverted CCl4-induced DEGs in a dose-dependent manner. qPCR analysis of S100 g, Sprr1, CCL3/7, Saa2/3, IL1rn, Cox7a2 and Rad15 confirmed RNA-Seq results. IPA showed that CCl4 treatment altered some signaling and metabolic pathways, which were ameliorated or returned to normal following DNLA treatment. The CCl4-activated mitochondrial oxidative phosphorylation was illustrated as an example. IPA Upstream Regulator Analysis further revealed the activated or inhibited molecules and chemicals that are responsible for CCl4-induced DEGs, and DNLA attenuated these changes. BSCE analysis verified that CCl4-induced DEGs were highly correlated with the GEO database of CCl4 hepatotoxicity in rodents, and DNLA dose-dependently attenuated such correlation. CONCLUSION: RNA-Seq revealed CCl4-induced DEGs, disruption of canonical pathways, activation or inhibition of upstream regulators, which are highly correlated with database for CCl4 hepatotoxicity. All these changes were attenuated or returned to normal by DNLA, demonstrating the mechanisms for DNLA to protect against CCl4 hepatotoxicity.


Assuntos
Alcaloides/química , Alcaloides/uso terapêutico , Intoxicação por Tetracloreto de Carbono/tratamento farmacológico , Intoxicação por Tetracloreto de Carbono/genética , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/genética , Dendrobium/química , RNA-Seq/métodos , Imunidade Adaptativa/efeitos dos fármacos , Animais , Intoxicação por Tetracloreto de Carbono/patologia , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Biologia Computacional , Bases de Dados Genéticas , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/química , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação Oxidativa/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
13.
Acta Diabetol ; 57(11): 1383-1393, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32647998

RESUMO

AIMS: Steroid diabetes mellitus (SDM) is a metabolic syndrome caused by an increase in glucocorticoids, and its pathogenesis is unclear. 18F-FDG PET/CT can reflect the glucose metabolism of tissues and organs under living conditions. Here, PET/CT imaging of SDM and type 2 diabetes mellitus (T2DM) rats was used to visualize changes in glucose metabolism in the main glucose metabolizing organs and investigate the pathogenesis of SDM. METHODS: SDM and T2DM rat models were established. During this time, PET/CT imaging was used to measure the %ID/g value of skeletal muscle and liver to evaluate glucose uptake. The pancreatic, skeletal muscle and liver were analyzed by immunohistochemistry. RESULTS: SDM rats showed increased fasting blood glucose and insulin levels, hyperplasia of islet α and ß cells, increased FDG uptake in skeletal muscle accompanied by an up-regulation of PI3Kp85α, IRS-1, and GLUT4, no significant changes in liver uptake, and that glycogen storage in the liver and skeletal muscle increased. T2DM rats showed atrophy of pancreatic islet ß cells and decreased insulin levels, significantly reduced FDG uptake and glycogen storage in skeletal muscle and liver. CONCLUSIONS: The pathogenesis of SDM is different from that of T2DM. The increased glucose metabolism of skeletal muscle may be related to the increased compensatory secretion of insulin. Glucocorticoids promote the proliferation of islet α cells and cause an increase in gluconeogenesis in the liver, which may cause increased blood glucose.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus/diagnóstico por imagem , Animais , Glicemia/metabolismo , Diabetes Mellitus/sangue , Diabetes Mellitus Tipo 2/sangue , Jejum/sangue , Fluordesoxiglucose F18/administração & dosagem , Glucocorticoides/metabolismo , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Glicogênio/metabolismo , Humanos , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Fígado/diagnóstico por imagem , Fígado/metabolismo , Masculino , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Ratos , Ratos Wistar
14.
ISA Trans ; 105: 367-376, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32532547

RESUMO

The inkjet 3D printing has been one of the most studied and applied additive manufacturing (AM) processes in electronic industry. In this AM process, the forming quality is greatly influenced by the micro-droplet deposition and substrate temperature. While most studies focus on the formation mechanism of droplets, there are few studies on the quantitative evaluation of the droplet surface profile and its qualitative correlation with temperature changes. In this study, the characteristics of droplet profile in three-dimensional inkjet printing were studied from two aspects, the modeling of droplet shape and the estimation of droplet temperature. For this purpose, different types of radial basis function networks (RBFN) are applied. The validity of the regularized RBFN model is developed and verified by experiments. The results show that the droplet shape can be accurately modeled and the drying temperature can be accurately estimated given the model.

15.
Biomed Pharmacother ; 129: 110351, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32535387

RESUMO

The activation of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated signaling pathway has been involved in the mechanisms of a variety of protective agents against cellular oxidative stress. We recently demonstrated that Dendrobium nobile Lindl. alkaloids (DNLA), the active ingredients of Dendrobium, protects mice from CCl4-induced liver injury, dependent on the Nrf2 signaling pathway. The present study was aimed to determine whether the protection against mitochondrial oxidative damage plays a role in the mode of action of DNLA on CCl4-induced liver injury, and to further investigate whether the DNLA-conferred mitochondrial beneficial effects is dependent on the activation of Nrf2 signaling. The CCl4-induced acute liver injury model was employed in both wild-type (WT) and Nrf2-knockout (Nrf2-/-) mice. The results showed that in WT mice DNLA reduced CCl4-induced liver injury, accompanied by a significant reduction in CCl4-induced mitochondrial oxidative stress as evidenced by a decrease in mitochondrial H2O2 content and MDA production, and a marked increase in GSH level and Mn-SOD activity. However, these protective effects were significantly attenuated in Nrf2-/- mice. Furthermore, the administration of DNLA improved mitochondrial oxygen consumption, elevated ATP production, and decreased CCl4-induced apoptosis in the WT mice, whereas the DNLA-mediated protections on mitochondrial function were diminished in the Nrf2 null mice. These results demonstrate that the improvement of mitochondrial oxidative stress and mitochondrial dysfunction is implicated in the mechanism of DNLA-mediated protection on CCl4-induced liver injury, and this DNLA-modulated mode of action is dependent on the activation of Nrf2 signaling pathway.


Assuntos
Alcaloides/farmacologia , Antioxidantes/farmacologia , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Dendrobium , Fígado/efeitos dos fármacos , Mitocôndrias Hepáticas/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Alcaloides/isolamento & purificação , Animais , Antioxidantes/isolamento & purificação , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Dano ao DNA/efeitos dos fármacos , Dendrobium/química , Modelos Animais de Doenças , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Knockout , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/patologia , Fator 2 Relacionado a NF-E2/deficiência , Fator 2 Relacionado a NF-E2/genética , Transdução de Sinais
16.
Biomed Pharmacother ; 117: 109073, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31212129

RESUMO

Dendrobium nobile Lindl. alkaloids (DNLA), the active ingredients of Dendrobium, has been shown to possess anti-oxidative effects. The nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant signaling pathway plays a critical role in the cellular response to oxidative stress. Oxidative damage has been implicated in the mechanism of various hepatotoxins induced liver injury. The present study aimed to examine the protective effects of DNLA on CCl4-induced acute liver injury, and to explore the role of the Nrf2 pathway in the protective action of DNLA. Wild-type (WT) and Nrf2-knockout (Nrf2-/-) mice were administrated with DNLA (20 mg/kg/day, ig) for 7 days, and then challenged with CCl4 (20 µL/kg, ip). In WT mice, DNLA reduced CCl4 induced liver injury, as evidenced by the reduction in the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), attenuation of malondialdehyde (MDA) production, and improved ultrastructural morphology in hepatocytes. However, the protective effect was diminished in Nrf2-/- mice, indicating an essential role of Nrf2 in DNLA-mediated protection over CCl4 liver injury. Furthermore, it was found that DNLA enhanced Nrf2 expression and nuclear accumulation and increased the expression of Nrf2 regulated downstream proteins. These results demonstrate that DNLA protects mice from CCl4 induced liver injury, probably through the activation of the Nrf2 signaling pathway.


Assuntos
Alcaloides/farmacologia , Dendrobium/química , Fígado/lesões , Fator 2 Relacionado a NF-E2/metabolismo , Substâncias Protetoras/farmacologia , Transdução de Sinais , Doença Aguda , Animais , Tetracloreto de Carbono , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/ultraestrutura , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/deficiência
17.
Nucl Med Commun ; 40(5): 539-544, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30973841

RESUMO

OBJECTIVE: This study aimed to present a proper understanding of the fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) value in localizing the primary lesion in adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome in a relatively large case cohort. PATIENTS AND METHODS: This retrospective study included 47 patients with ACTH-dependent Cushing syndrome, who underwent an F-FDG PET/CT examination in our hospital from November 2010 to January 2018. The serum cortisol, 24 h urine cortisol, serum ACTH, and high-dose dexamethasone suppression test were measured in all the patients. Bilateral inferior petrosal sinus sampling was performed in 28/47 patients. Pituitary magnetic resonance imaging and whole-body F-FDG PET/CT were performed in all patients. RESULTS: Serum ACTH at 8 a.m. higher than 161.8 pg/ml as the cut-off value showed the best diagnostic accuracy (73.9%) for the successful localization of the primary lesions. In Cushing disease patients, the pituitary maximum standardized uptake value F-FDG PET/CT (n=11) did not show significant differences compared with that in ectopic ACTH syndrome (EAS) patients (n=20). In terms of EAS, the descending order of maximum standardized uptake value was 13.2±8.3 (4.8-26.4) in pancreatic neuroendocrine tumors (n=4), 7.1±2.4 (3.5-10.1) in mediastinal carcinoid (n=11), and 2.0±0.1 (1.9-2.2) in bronchial carcinoid (n=4). This study first reported the F-FDG PET/CT images of ACTH-secreting olfactory neuroblastoma. CONCLUSION: Serum ACTH level determines the success rate of localization of the primary ACTH-secreting tumor in ACTH-dependent syndrome. F-FDG PET/CT plays a role in localizing the site for EAS, although it plays a limited role in Cushing disease.


Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Síndrome de Cushing/diagnóstico por imagem , Síndrome de Cushing/metabolismo , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
18.
Appl Microbiol Biotechnol ; 103(3): 1311-1324, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30560451

RESUMO

Radiolabelled ligands of glucagon-like peptide 1 receptor (GLP-1R) have been used to image the GLP-1R-expressing tissues (e.g., islets and insulinoma). Here, we introduced human glucagon-like peptide 1 receptor (hglp-1r) gene as a novel radionuclide reporter gene to broaden its applications in molecular imaging in vivo. Transient and stable baculoviral vectors (BV) were re-constructed and used to transfer the hglp-1r gene or enhanced green fluorescent protein (egfp) reporter gene into the stem cells or tumor cells. Cell proliferation assay and flow cytometry analysis demonstrated that BV-mediated reporter gene transferring and expression was biosafe and highly efficient. The BV-mediated exogenous hGLP-1R in target cells showed same ligand-receptor binding characteristics compared with its counterpart in insulinoma cells. Furthermore, the ligand-receptor binding assay showed a high affinity (IC50 = 0.3708 nM) and robust correlation (R2 = 0.9264) between the fluorescein-tagged or radiolabeled ligand probes and exogenous hGLP-1R in target cells. The target cells transferred with BV-mediated hGLP-1R could be clearly visualized in nude mice by micro-PET, which was capable of the purposes of short-term tracking transplanted stem cells or long-term monitoring tumor formation. Then, the image-based analysis and bio-distribution analysis quantitatively confirmed high target-to-background ratio of hGLP-1R-expressing cells. This study also investigated the endogenous GLP-1R-expressing organs/tissues in nude mice in the hGLP-1R radionuclide reporter gene imaging. Summarily, we evaluated the utility of hglp-1r gene as a novel radionuclide reporter gene, and demonstrated that it was a favorable and promising candidate of molecular imaging tool, which would expand the spectrum of radionuclide reporter gene imaging systems.


Assuntos
Genes Reporter/genética , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Células-Tronco Mesenquimais/citologia , Imagem Molecular/métodos , Ensaio Radioligante/métodos , Animais , Baculoviridae/genética , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Fluorescência Verde/genética , Humanos , Insulinoma , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Radioisótopos , Transplante de Células-Tronco
19.
Appl Microbiol Biotechnol ; 102(4): 1933-1943, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29356866

RESUMO

Reporter gene imaging is widely used for non-invasively detecting tumorigenesis, trafficking therapeutic cells, and monitoring treatment effect. Baculoviral vectors (BVs) have been utilized as transgenic vectors in the reporter gene imaging systems in recent years. However, BV-mediated report gene imaging can only provide short-term investigation due to its transient transgene expression, which is incompetent for the long-term applications. In the current study, we reconstructed a series of hybrid BVs with several elements, to investigate the feasibility of this hybrid BV-mediated long-term reporter gene imaging in vivo. We showed that with the indispensable assistance of a positive-selection process, hybrid BV containing Sleeping Beauty 100× (SB) transposon system (BV-SB) could significantly prolong the enhanced green fluorescent protein (eGFP) expression for at least 180 days in vitro at nearly 100% eGFP positive percentage and over 1011 arbitrary unit total fluorescence intensity, whereas other hybrid BV-mediated transgene expression gradually faded in only 20 days. Furthermore, BV-SB-mediated eGFP fluorescent reporter gene imaging monitored tumorigenesis in the nude mice for at least 35 days. In addition, we exploited the glucagon-like peptide 1 receptor (glp-1r) gene as a radionuclide reporter gene for in vivo micro-PET imaging. At 50th day post-tumor transplantation, the micro-PET imaging showed considerable radiotracer-receptor-binding in vivo, resulted by stable high level of BV-SB-mediated GLP-1R expression in tumor. In summary, we retrofitted BV with the SB transposon system to make it competent for the long-term reporter gene imaging in vivo, which might broaden the application scopes of BV in the long-term molecular imaging and other biomedicine research fields.


Assuntos
Baculoviridae/genética , Elementos de DNA Transponíveis , Genes Reporter , Proteínas de Fluorescência Verde/análise , Imagem Óptica/métodos , Recombinação Genética , Coloração e Rotulagem/métodos , Animais , Carcinogênese , Quimera , Modelos Animais de Doenças , Expressão Gênica , Receptor do Peptídeo Semelhante ao Glucagon 1/análise , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Proteínas de Fluorescência Verde/genética , Camundongos Nus , Neoplasias/patologia , Neoplasias/fisiopatologia , Tomografia por Emissão de Pósitrons , Fatores de Tempo
20.
J Thorac Dis ; 10(12): 6557-6562, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30746200

RESUMO

BACKGROUND: We previously reported the techniques for total endoscopic atrial septal defect (ASD) repair on hearts arrested with cardioplegia through three small incisions in the chest wall without aid of a surgical robotic system. The optimal results motivated us to use total thoracoscopic technology for ASD on perfused beating hearts. METHODS: From 2010 to 2017, 161 patients with a mean age of 28.31±12.34 years who underwent non-robotically assisted total thoracoscopic closure for ASD were included in this study, and those patients were also divided into two groups, including group A and group B. In group A, 115 patients underwent the procedure on beating hearts without aorta cross-clamped; in group B, 46 patients underwent the procedure on hearts arrested with cardioplegia with aorta cross-clamped. Cardiopulmonary bypass (CPB) was peripherally achieved as well. RESULTS: Total thoracoscopic ASD closures were successfully performed without in-hospital mortality or other serious complications in all patients of both groups. Dacron or bovine patches were used in 81 and 32 patients in the two groups, respectively. Duration of operation, duration of CPB, aorta cross-clamped time, duration of mechanical ventilation, the length of intensive care unit (ICU) and post-operative hospital stay in group A, were all shorter than those in group B (P<0.05). There was no statistically significant difference in blood transfusion during operation or post-operation thoracic drainage. During follow-up, echocardiograms at 3, 30, 90 and 365, showed no residual shunt or tricuspid regurgitation. CONCLUSIONS: Total thoracoscopic closure of ASD without assistance of a surgical robotic system on beating heart is safe and feasible and can be used as a therapeutic option for ASD, and by using the mentioned technique, less injuries are applied to patients.

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