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The nutritional and functional properties of leaf proteins is a decisive factor for their use in food. This work was aimed to extract defatted Artemisia capillaris Thunb. (ACD) leaf proteins (ACLP), and assess ACLP nutritional quality, functional properties and in vitro antioxidant activity, as well characterize the structure. ACLP had a balanced amino acid profile and high bioavailability (protein digestibility corrected amino acid score (PDCAAS) 99.29 %). Solubility, foaming capacity and emulsifying ability of ACLP correlated positively with pH. Water and oil holding capacity were increased with temperature. Gel electrophoresis shown the protein molecular size was mainly â¼25 kDa, and random coil was the mainly secondary structure while ß-sheet was dominant regular conformation as indicated by circular dichroism (CD). ACLP performed in vitro antioxidant activity which was better after digestion. All data implied ACLP met the WHO/FAO protein quality expectations and had application potential in food.
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BACKGROUND: Pathologic complete response (pCR) following preoperative systemic therapy is associated with improved outcomes after subsequent liver transplant/resection in hepatocellular carcinoma (HCC). However, the relationship between radiographic and histopathological response remains unclear. METHODS: We retrospectively examined patients with initially unresectable HCC who received tyrosine kinase inhibitor (TKI) plus anti-programmed death 1 (PD-1) therapy before undergoing liver resection between March 2019 and September 2021 across 7 hospitals in China. Radiographic response was evaluated using mRECIST. A pCR was defined as no viable tumor cells in resected samples. RESULTS: We included 35 eligible patients, of whom 15 (42.9%) achieved pCR after systemic therapy. After a median follow-up of 13.2 months, tumors recurred in 8 non-pCR and 1 pCR patient. Before resection, there were 6 complete responses, 24 partial responses, 4 stable disease cases, and 1 progressive disease case, per mRECIST. Predicting pCR by radiographic response yielded an area under the receiver operating characteristic curve (AUC) of 0.727 (95% CI: 0.558-0.902), with an optimal cutoff value of 80% reduction in the enhanced area in MRI (called major radiographic response), which had a 66.7% sensitivity, 85.0% specificity, and a 77.1% diagnostic accuracy. When radiographic response was combined with α-fetoprotein response, the AUC was 0.926 (95% CI: 0.785-0.999); the optimal cutoff value was 0.446, which had a 91.7% sensitivity, 84.6%, specificity, and an 88.0% diagnostic accuracy. CONCLUSIONS: In patients with unresectable HCC receiving combined TKI/anti-PD 1 therapy, major radiographic response alone or combined with α-fetoprotein response may predict pCR.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , alfa-Fetoproteínas , Estudos Retrospectivos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Recidiva Local de Neoplasia/diagnóstico por imagem , Imunoterapia , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
BACKGROUND: Lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEICC) has been recently introduced as a genetically distinct of intrahepatic cholangiocarcinoma (ICC). We aimed to investigate whether LEICC has distinct radiological characteristics in comparison with classical ICC, and to determine MRI features that can be used to differentiate LEICC from classical ICC. METHODS: Five hundred and sixty-seven consecutive patients who underwent surgical resection or liver transplantation for ICC between 2014 and 2021 were retrospectively identified. Among them, 30 patients with LEICC (LEICC-cohort) and 116 with stage-matched classical ICC (control-cohort) were finally included. Pre-operative MRI data were compared between the two cohorts. Multivariable logistic regression analysis was performed to determine relevant imaging features suggesting the diagnosis of LEICC over classical ICC. RESULTS: LEICCs showed significantly higher frequencies of a non-rim arterial phase hyperenhancement (APHE), washout on post-arterial images and a smooth margin, as well as less frequencies of perilesional enhancement and liver capsular retraction when compared with classical ICCs (P < 0.05 for all). The multivariate analysis revealed that non-rim APHE (odds ratio, 10.863; 95% CI [3.295-35.821]; P < 0.001) and the absence of perilesional enhancement (odds ratio, 3.350; 95% CI [1.167-9.619]; P = 0.025) are significant independent imaging features that suggest the diagnosis of LEICCs over classical ICCs. CONCLUSIONS: Compared with classical ICCs, LEICCs do have distinct radiological characteristics. A smooth margin, non-rim APHE, washout on post-arterial images, absent perilesional enhancement and absent liver capsular retraction are useful MRI features that could help to differentiate LEICCs from classical ICCs.
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Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Estudos Retrospectivos , Meios de Contraste , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos , Ductos Biliares Intra-Hepáticos/patologia , Carcinoma Hepatocelular/patologiaRESUMO
In recent years, research on the interaction between flavonoids and intestinal microbes have prompted a rash of food science, nutriology and biomedicine, complying with future research trends. The gut microbiota plays an essential role in the maintenance of intestinal homeostasis and human health, but once the intestinal flora dysregulation occurs, it may contribute to various diseases. Flavonoids have shown a variety of physiological activities, and are metabolized or biotransformed by gut microbiota, thereby producing new metabolites that promote human health by modulating the composition and structure of intestinal flora. Herein, this review demonstrates the key notion of flavonoids as well as intestinal microbiota and dysbiosis, aiming to provide a comprehensive understanding about how flavonoids regulate the diseases by gut microbiota. Emphasis is placed on the microbiota-flavonoid bidirectional interaction that affects the metabolic fate of flavonoids and their metabolites, thereby influencing their metabolic mechanism, biotransformation, bioavailability and bioactivity. Potentially by focusing on the abundance and diversity of gut microbiota as well as their metabolites such as bile acids, we discuss the influence mechanism of flavonoids on intestinal microbiota by protecting the intestinal barrier function and immune system. Additionally, the microbiota-flavonoid bidirectional interaction plays a crucial role in regulating various diseases. We explain the underlying regulation mechanism of several typical diseases including gastrointestinal diseases, obesity, diabetes and cancer, aiming to provide a theoretical basis and guideline for the promotion of gastrointestinal health as well as the treatment of diseases.
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The role of NOD-like receptor protein 3 (NLRP3)-mediated macrophages pyroptosis in acute lung injury (ALI) is well-established. Quercetin (Que) is a natural bioflavonoid compound with anti-inflammatory and antioxidative properties that reportedly inhibits the NLRP3 inflammasome in sepsis-induced organ dysfunctions such as ALI. However, the mechanism underlying the inhibitory effect of quercetin on NLRP3 activation remains unclear. In this study, we established an endotoxin-induced ALI mouse model with an in vitro LPS challenge. We demonstrated that the administration of quercetin could significantly reduce pulmonary injury and decrease the production of pro-inflammatory cytokines. Moreover, we found that quercetin could inhibit the activation of the NLRP3 inflammasome by suppressing the nuclear accumulation of PKM2 and increasing SIRT1 levels. Importantly, treatment with SRT1720 (a specific SIRT1 activator) could inhibit the nuclear accumulation of PKM2 and the activation of NLRP3. Besides, preventing PKM2 dimerization with ML265 yielded an anti-inflammatory effect, similar to findings observed for SRT1720. In addition, we found that SIRT1 silencing or inhibition by EX527 could increase NLRP3 activation and nuclear accumulation of PKM2 and override quercetin-mediated anti-inflammatory activity. These findings indicated that quercetin could downregulate NLRP3 inflammasome activation by inhibiting the nuclear accumulation of PKM2 and upregulating SIRT1 expression, expanding the treatment landscape for ARDS.
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Lesão Pulmonar Aguda , Inflamassomos , Animais , Camundongos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/prevenção & controle , Anti-Inflamatórios/uso terapêutico , Inflamassomos/metabolismo , Lipopolissacarídeos/toxicidade , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Quercetina/farmacologia , Quercetina/uso terapêutico , Sirtuína 1RESUMO
OBJECTIVE: To observe the effect of acupuncture combined with regular treatment and swallowing function training on pharyngeal motor, sensory function and penetration-aspiration function in patients with dysphagia after stroke. METHODS: A total of 60 patients with dysphagia after stroke were randomly divided into a control group and an observation group, 30 patients in each group. Both groups were treated with conventional treatment and swallowing function training; in addition, the observation group was treated with acupuncture at Lianquan (CV 23), Fengfu (GV 16), Yifeng (TE 17). All the treatments were given once a day, 5 days a week, for totally 4 weeks. In the two groups, the pharyngeal motor and sensory function, penetration-aspiration scores were evaluated by fiberoptic endoscopic evaluation of swallowing (FEES), and the Kubota water swallowing test scores were assessed before and after treatment, and the clinical effects were compared. RESULTS: After treatment, the pharyngeal motor and sensory function in the two groups were all higher than those before treatment (P<0.05), and those in the observation group were better than the control group (P<0.05). After treatment, the penetration-aspiration scores and Kubota water swallowing test scores in the two groups were all lower than those before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). The total effective rate was 93.3% (28/30) in the observation group, which was better than 73.3% (22/30) in the control group (P<0.05). CONCLUSION: Acupuncture combined with regular treatment and swallowing training could improve the pharyngeal motor and sensory function, and penetration-aspiration scores in patients with dysphagia after stroke.
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Terapia por Acupuntura , Transtornos de Deglutição , Acidente Vascular Cerebral , Pontos de Acupuntura , Deglutição , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Humanos , Acidente Vascular Cerebral/complicações , Resultado do Tratamento , ÁguaRESUMO
BACKGROUND: Taxifolin is a natural dihydroflavonol found in many plants and health products. In the present study, its anti-obesity and gut microbiota modulating effects were studied. C57BL/6J mice were fed with a high-fat diet (HFD) supplemented with taxifolin (0, 0.5 and 1 mg mL-1 , respectively) in drinking water for 15 weeks. RESULTS: Taxifolin supplementation showed no influence on food and water intake. However, it decreased body weight gain, inhibited fat accumulation, and decreased total cholesterol and triacylglycerol level in mice liver. Taxifolin enhanced superoxide dismutase (SOD) activity in mice liver, which in turn protected the liver from lipid peroxidation damage. It also improved insulin resistance in obese mice. Metagenomic analysis of bacterial 16S rRNA demonstrated that HFD decreased gut microbiota diversity and caused dysbiosis. However, taxifolin improved the gut microbiota diversity and decreased the Firmicutes/Bacteroidetes ratio. In particular, it inhibited Proteobacteria from blooming, this being a signature of dysbiosis in gut microbiota. CONCLUSION: Taxifolin ameliorated the symptoms of obesity, hepatic steatosis, lipid peroxidation, insulin resistance, and gut microbiota dysbiosis in HFD fed C57BL/6J mice. © 2021 Society of Chemical Industry.
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Dieta Hiperlipídica , Microbioma Gastrointestinal , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Quercetina/análogos & derivados , RNA Ribossômico 16SRESUMO
SCOPE: Alzheimer's disease (AD) is a neurodegenerative disease with phenomena of cognitive impairments. Oxidative stress and cholinergic system dysfunction are two widely studied pathogenesis of AD. Dihydromyricetin (DMY) is a natural dihydroflavonol with many bioactivities. In this study, it is aimed to investigate the effects of DMY on cognitive impairment in d-galactose (d-gal) induced aging mice. METHODS AND RESULTS: Mice are intraperitoneally injected with d-gal for 16 weeks, and DMY is supplemented in drinking water. The results show that DMY significantly improves d-gal-induced cognitive impairments in novel object recognition and Y-maze studies. H&E and TUNEL staining show that DMY could improve histopathological changes and cell apoptosis in mice brain. DMY effectively induces the activities of catalase, superoxide dismutase and glutathione peroxidase, and reduces malondialdehyde level in mice brain and liver. Furthermore, DMY reduces cholinergic injury by inhibiting the activity of Acetylcholinesterase (AChE) in mice brain. In vitro studies show that DMY is a non-competitive inhibitor of AChE with IC50 value of 161.2 µg mL-1 . CONCLUSION: DMY alleviates the cognitive impairments in d-gal-induced aging mice partly through regulating oxidative stress and inhibition of acetylcholinesterase.
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Disfunção Cognitiva , Doenças Neurodegenerativas , Acetilcolinesterase/efeitos adversos , Acetilcolinesterase/metabolismo , Envelhecimento , Animais , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Flavonóis , Galactose/efeitos adversos , Camundongos , Estresse OxidativoAssuntos
Escabiose , Idoso de 80 Anos ou mais , Animais , Centenários , Humanos , Sarcoptes scabiei , Escabiose/diagnóstico por imagemRESUMO
Reprogrammed cell metabolism is a well-accepted hallmark of cancer. Metabolism changes provide energy and precursors for macromolecule biosynthesis to satisfy the survival needs of cancer cells. The specific changes in different aspects of lipid metabolism in cancer cells have been focused in recent years. These changes can affect cell growth, proliferation, differentiation and motility through affecting membranes synthesis, energy homeostasis and cell signaling. The tumor suppressor p53 plays vital roles in the control of cell proliferation, senescence, DNA repair, and cell death in cancer through various transcriptional and non-transcriptional activities. Accumulating evidences indicate that p53 also regulates cellular metabolism, which appears to contribute to its tumor suppressive functions. Particularly the role of p53 in regulating lipid metabolism has gained more and more attention in recent decades. In this review, we summarize recent advances in the function of p53 on lipid metabolism in cancer. Further understanding and research on the role of p53 in lipid metabolism regulation will provide a potential therapeutic window for cancer treatment.
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Suscetibilidade a Doenças , Metabolismo dos Lipídeos , Neoplasias/etiologia , Neoplasias/metabolismo , Proteína Supressora de Tumor p53/genética , Tecido Adiposo/metabolismo , Animais , Transporte Biológico , Colesterol/metabolismo , Metabolismo Energético , Ácidos Graxos/metabolismo , Humanos , Espaço Intracelular/metabolismo , Lipólise , Neoplasias/patologia , Oxirredução , Proteína Supressora de Tumor p53/metabolismoRESUMO
Three shell materials, lecithin (ZNP-L), chitosan (ZNP-CH) and sodium caseinate (ZNP-SC), were used to prepare core-shell zein nanoparticles. Astilbin was encapsulated as a model flavonoid to compare the influence of the shell materials on zein nanoparticles both in vitro and in vivo. The particle size was moderately increased by lecithin and sodium caseinate, but notably increased by chitosan. All the shell materials provided good redispersibility for the nanoparticles and significantly improved the colloidal stability. Chitosan and sodium caseinate significantly delayed and decreased the feces excretion of astilbin in rats, while lecithin exhibited a very weak effect. The results may be attributed to the difference in mucoadhesive properties between the shell materials. As a consequence, the bioavailability values of astilbin in rats were 18.2, 9.3 and 1.89 times increased through ZNP-CH, ZNP-SC and ZNP-L compared with that of free astilbin, respectively.
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Flavonoides/farmacologia , Flavonóis/farmacologia , Nanocápsulas/química , Animais , Disponibilidade Biológica , Caseínas/química , Quitosana/química , Feminino , Flavonoides/química , Flavonóis/química , Lecitinas/química , Ratos , Ratos Sprague-DawleyRESUMO
Bambusa multiplex cv Fernleaf (B. multiplex) is a species of bamboo. In the present study, B. multiplex leaf extract was prepared through the resin absorption/desorption procedure and analyzed by HPLC. C-Glycosyl flavonoids are the main constituents of B. multiplex extract, and the content of isoorientin and vitexin was 51.8 and 23.1 mg g-1, respectively. Besides, the extract exhibited inhibitory activities on pancreatic lipase and α-glucosidase with IC50 values of 0.91 and 1.16 mg mL-1, respectively. The extract could bind to pancreatic lipase and showed mixed-type inhibition. An in vivo study showed that pre-administration of B. multiplex extract significantly reduced the fat absorption in rats and increased fat excretion through feces. The change in the C-glycosyl flavonoid content in feces was the same as that in the triglyceride content. The inhibitory activity of B. multiplex leaf extract on pancreatic lipase was confirmed both in vitro and in vivo.
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Bambusa , Lipase/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Flavonoides/farmacologia , Modelos Animais , RatosRESUMO
Selenoprotein V (SELENOV) is a new and the least conserved member of the selenoprotein family. Herein we generated Selenov knockout (KO) mice to determine its in vivo function. The KO led to 16-19% increases (P < 0.05) in body weight that were largely due to 54% higher (P < 0.05) fat mass accumulation, compared with the wild-type (WT) controls. The extra fat accumulation in the KO mice was mediated by up-regulations of genes and proteins involved in lipogenesis (Acc, Fas, Dgat, and Lpl; up by 40%-1.1-fold) and down-regulations of lipolysis (Atgl, Hsl, Ces1d, and Cpt1a; down by 36-89%) in the adipose tissues. The KO also decreased (P < 0.05) VO2 consumption (14-21%), VCO2 production (14-16%), and energy expenditure (14-23%), compared with the WT controls. SELENOV and O-GlcNAc transferase (OGT) exhibited a novel protein-protein interaction that explained the KO-induced decreases (P < 0.05) of OGT protein (15-29%), activity (33%), and function (O-GlcNAcylation, 10-21%) in the adipose tissues. A potential cascade of SELENOV-OGT-AMP-activated protein kinase might serve as a central mechanism to link the biochemical and molecular responses to the KO. Overall, our data revealed a novel in vivo function and mechanism of SELENOV as a new inhibitor of body fat accumulation, activator of energy expenditure, regulator of O-GlcNAcylation, and therapeutic target of such related disorders.
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Metabolismo Energético , Lipólise , Tecido Adiposo/metabolismo , Animais , Peso Corporal , Metabolismo Energético/genética , Camundongos , Camundongos KnockoutRESUMO
BACKGROUND: We evaluated organ-specific response rates (OSRRs) to first-line lenvatinib plus anti-PD-1 antibodies in patients with advanced hepatocellular carcinoma (HCC). METHODS: This retrospective analysis included Chinese patients with unresectable/advanced HCC who received first-line lenvatinib (8 mg/day) plus ≥3 infusions of anti-PD-1 antibodies between October 2018 and May 2020. Tumor and macrovascular tumor thrombi (MVTT) treatment responses were evaluated every 2 months using RECIST v1.1. The overall response rate (ORR)/OSRR was defined as the percentage of patients with a best overall response of complete or partial response (CR or PR). RESULTS: In total, 60 patients were included in the analysis; 96.7% had measurable intrahepatic lesions, 55% had MVTT and 26.7% had extrahepatic disease. In all 60 patients, the ORR was 33.3%, median progression-free survival was 7.0 months (95% CI, 1.7-12.3) and median overall survival was not reached. The OSRR for MVTT (54.5%) was higher versus intrahepatic tumors (32.8%), extrahepatic lung metastases (37.5%) and lymph node metastases (33.3%). Among 33 patients with intrahepatic tumors and MVTT, 18 had differential responses in each site, including 13 with a better response in MVTT versus intrahepatic lesions. Among 18 patients whose MVTT achieved a radiographic CR or PR, six underwent surgical resection: 4/6 achieved a pathological CR in MVTT and 2/6 in the intrahepatic tumor. CONCLUSIONS: First-line lenvatinib plus anti-PD-1 antibodies resulted in better tumor responses in MVTT versus intrahepatic lesions. Complete MVTT necrosis may allow downstaging and subsequent eligibility for surgical resection in a proportion of patients with advanced HCC.
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Polygonatum cyrtonema is a famous bulk medicinal material which is the medicinal and edible homologous. With the implementation of the traditional Chinese medicine industry to promote precise poverty alleviation, the planting area of P. cyrtonema in Jinzhai is becoming larger and larger in recent years. Jinzhai is located in the Dabie Mountainous area, which is the largest mountain area and county in Anhui Province. The cultivation of P. cyrtonema is scattered, and the traditional Chinese medicine resources investigation is not only inefficient and accurate. In this study,the "Resource 3"(ZY-3) remote sensing image was used as the best observation phase,and the method of support vector machine classification was used. The method of parallelepiped, minimum distance, mahalanob is distance, maximum likelihood classification and neural net were used to classify and recognize the P. cyrtonema in the whole region. In order to determine the accuracy and reliability of classification results, the accuracy of six supervised classification results was evaluated by confusion matrix method, and the advantages and disadvantages of six supervised classification methods for extracting P. cyrtonema field planting area were compared and analyzed. The results showed that the method of support vector machine classification was more appropriate than that using other classification methods. It provides a scientific basis for monitoring the planting area of P. cyrtonemain field.
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Polygonatum , Medicina Tradicional Chinesa , Reprodutibilidade dos Testes , Projetos de Pesquisa , Máquina de Vetores de SuporteRESUMO
Aconitum L., the main source of Aconitum medicinal materials, is rich in diterpenoid alkaloids. Several drugs derived from diterpenoid alkaloids are widely used to the current clinical treatment of pain, inflammation, and other symptoms. This paper aims to clarify the main metabolites and distribution of diterpenoid alkaloids in different parts of Aconitum plants. To that end, 7 species of Aconitum from three subgenera were analyzed by UHPLC-Q-TOF-MS under identical conditions. The fragmentation regularity of various types of diterpene alkaloids were determined and a total of 126 metabolites were identified by comparing the reference material and secondary mass spectrometry, with the literature. 67, 49, 17, 41, 14, 17 and 21 metabolites were identified from Aconitum carmichaeli, Aconitum stylosum, Aconitum sinomontanum, Aconitum vilmorinianum, Aconitum pendulum, Aconitum tanguticum and Aconitum gymnandrum, respectively. Meanwhile, the structure type of A. carmichaeli, A. stylosum, A. vilmorinianum, A. pendulum, A. gymnandrum were identified as C19 type, A. sinomontanum was C18 type, while A. tanguticum was C20 type. A high similarity of metabolites was found between A. stylosum and A. vilmorinianum. The quantitative analysis of 19 compounds and the relative peak area of all metabolites which obtained through internal standard berberine, highlighted compounds like karakoline, talatisamine and atisine as references for future study of metabolic pathways. Furthermore, results from metabolites distribution and relative peak area analysis suggest that the leaf of A. carmichaeli, the leaf and stem of A. stylosum and A. vilmorinianum, and the flower of A. pendulum have potential as medicinal resources and are worth further development. These results establish a foundation for the comprehensive utilization of Aconitum resources.
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Aconitum , Alcaloides , Diterpenos , Cromatografia Líquida de Alta Pressão , Diterpenos/análise , Raízes de Plantas/químicaRESUMO
PURPOSE: To analyze the correlation between enhancement patterns of small hepatic carcinomas (HCCs; ≤ 30 mm) on contrast-enhanced ultrasound (CEUS) and the clinicopathologic characteristics. METHODS: The retrospective study included 346 inpatients (288 males and 58 females) with 372 pathologically confirmed small HCCs between January 2017 and December 2018. All patients underwent CEUS examination before pathological examination. Statistical analysis was used to determine the correlation between enhancement patterns of small HCCs on CEUS and clinicopathologic characteristics including serum alpha-feto-protein level, protein induced by vitamin K absence or antagonist-II (PIVKA-II) level, primary or recurrent HCC condition, tumor number, tumor differentiation, tumor size, liver background and microvascular invasion (MVI). RESULTS: Three hundred forty-seven out of 372 (93.3 %) HCCs manifested arterial phase hyper-enhancement (APHE). The arterial enhancement patterns were correlated with the tumor differentiation (odds ratio = 10.336, P = 0.000). Moderately- or poorly-differentiated HCCs were more likely to display APHE than well-differentiated HCCs (96.2 % vs 58.6 %, P < 0.001). Two hundred ninety-five of 372 (79.3 %) HCCs showed washout in the portal venous/late phase. Washout was correlated with serum PIVKA-II level, tumor size, tumor differentiation, and MVI on univariate analysis (P < 0.05). Logistic regression analysis revealed that only tumor size was significantly associated with washout of small HCCs (odds ratio = 2.335, P = 0.006). Large HCCs (20-30 mm) displayed a higher proportion of washout compared with that of HCCs ≤ 20 mm. CONCLUSIONS: Enhancement patterns of small HCCs on CEUS were significantly correlated with tumor size and tumor differentiation among all clinicopathologic characteristics.
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Carcinoma Hepatocelular/diagnóstico por imagem , Aumento da Imagem , Neoplasias Hepáticas/diagnóstico por imagem , Ultrassonografia , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfolipídeos , Estudos Retrospectivos , Hexafluoreto de Enxofre , Adulto JovemRESUMO
Selenoprotein V (SELENOV) contains a thioredoxin-like fold and a conserved CxxU motif with a potential redox function. This study was to assess its in vivo and in vitro roles and mechanisms in coping with different oxidant insults. In Experiment (Expt.)1, SELENOV knockout (KO) and wild type (WT) mice (male, 8-wk old) were given an ip injection of saline, diquat (DQ, 12.5 mg/kg), or N-acetyl-para-aminophenol (APAP, 300 mg/kg) (n = 10), and killed 5 h after the injection. In Expt. 2, primary hepatocytes of WT and KO were treated with DQ (0-0.75 mM) or APAP (0-6 mM) for 12 h. In Expt. 3, 293 T cells overexpressing Selenov gene (OE) were treated with APAP (0-4 mM) for 24 h or H2O2 (0-0.4 mM) for 12 h. Compared with the WT, the DQ- and APAP-injected KO mice had higher (P < 0.05) serum alanine aminotransferase activities and hepatic malondialdehyde (MDA), protein carbonyl, endoplasmic reticulum (ER) stress-related proteins (BIP and CHOP), apoptosis-related proteins (FAK and caspase-9), and 3-nitrotyrosine, along with lower total anti-oxidizing-capability (T-AOC) and severer hepatic necrosis. Likewise, the DQ and APAP-treated KO hepatocytes had elevated (P < 0.05) cell death (10-40%), decreased (P < 0.05) T-AOC (63-83%), glutathione (26-87%), superoxide dismutase (SOD) activity (28-36%), mRNA levels of redox enzymes (Cat, Gcs, Gpx3, and Sod) and (or) sharper declines (P < 0.05) in cellular respiration and ATP production than that of the WT cells. In contrast, the OE cells had greater viability and T-AOC and lower MDA, and carbonyl contents after the APAP and H2O2 exposures (all at P < 0.05) than the controls. Moreover, the OE cells had greater (P < 0.05) redox enzyme activities (GPX, TrxR, and SOD), and lower (P < 0.05) expressions of ER stress-related genes (Atf4, Atf6, Bip, Xbp1t, Xbp1s, and Chop) and proteins (BIP, CHOP, FAK, and caspase-9) than the control cells after the treatment of H2O2 (0.4 mM). In conclusion, SELENOV conferred protections in vivo and in vitro against the reactive oxygen and nitrogen species-mediated ER stress-related signaling and oxidative injuries.
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Doença Hepática Induzida por Substâncias e Drogas , Estresse do Retículo Endoplasmático , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/toxicidade , Fígado/metabolismo , Masculino , Camundongos , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Selenoproteínas/genética , Selenoproteínas/metabolismoRESUMO
OBJECTIVES: To explore the enhancement features of early hepatocellular carcinoma (HCC, including well-differentiated HCC and high-grade dysplastic nodules with a focus of HCC) and high-grade dysplastic nodules (HGDNs) on contrast-enhanced ultrasound (CEUS), correlated with the histopathologic findings. METHODS: This retrospective study enrolled 81 patients with 85 pathologically confirmed hepatic lesions (69 early HCCs and 16 HGDNs). All of the hepatic lesions were examined by CEUS with SonoVue (Bracco SpA, Milan, Italy) before surgery or biopsy. The enhancement features of early HCCs and HGDNs were evaluated and compared with histopathologic findings. RESULTS: Thirty-eight (55.1%) early HCCs showed arterial-phase hyperenhancement (APHE). The major enhancement pattern of early HCCs was APHE without portal venous/late-phase wash-out (20 of 69 [29.0%]). Eight (11.6%) early HCCs manifested APHE. Wash-out was observed in 30 (43.5%) early HCCs. Sixteen (23.2%) early HCCs showed very-late wash-out (>120 seconds). Wash-out was not observed in all HGDNs. Of the 16 HGDNs, arterial-phase isoenhancement without portal venous/late-phase wash-out was the major enhancement pattern (n = 7 [43.8%]). The degree of CD34 expression of sinusoidal endothelial cells was more diffuse in early HCCs than in HGDNs (56.5% versus 12.5%; P = .001). Arterial-phase enhancement patterns of early HCCs on CEUS were correlated with the degree of CD34 expression (P = .039). CONCLUSIONS: Enhancement patterns were significantly different between early HCCs and HGDNs on CEUS. Diffuse CD34 expression of sinusoidal endothelial cells in early HCC was correlated with APHE on CEUS.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Células Endoteliais , Humanos , Itália , Neoplasias Hepáticas/diagnóstico por imagem , Estudos Retrospectivos , UltrassonografiaRESUMO
We present a systematic study on the effects of CF4 plasma immersion ion implantation (PIII) in Si on the phase evolution of ultra-thin Ni silicides. For 3 nm Ni, NiSi2 was formed on Si substrates with and without CF4 PIII at temperature as low as 400 °C. For 6 nm Ni, NiSi was formed on pure Si, while epitaxial NiSi2 was obtained on CF4 PIII Si. The incorporation of C and F atoms in the thin epitaxial NiSi2 significantly reduces the layer resistivity. Increasing the Ni thickness to 8 nm results in the formation of NiSi, where the thermal stability of NiSi, the NiSi/Si interface and Schottky contacts are significantly improved with CF4 PIII. We suggest that the interface energy is lowered by the F and C dopants present in the layer and at the interface, leading to phase evolution of the thin Ni silicide.