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1.
Strahlenther Onkol ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869645

RESUMO

OBJECTIVE: To explore the clinical and imaging features of nasopharyngeal cancer (NPC) complicated by acute carotid blowout syndrome (CBS), analyze the risk factors for CBS, and improve diagnostic vigilance for early intervention. METHODS: This retrospective review was conducted between January 2003 and May 2023. Altogether, 49 patients with post-irradiation NPC with CBS and 49 patients without CBS as control group were enrolled. The condition of the patients when CBS occurred was reviewed. Patient characteristics of the CBS and control groups were compared, and binary logistic regression analysis was performed to identify risk factors for CBS. RESULTS: All patients in the CBS group were conscious, and 41 patients had a Karnofsky performance assessment scale score of ≥ 70. After interventional therapy, 43 patients survived (the mean survival time of patients after CBS was 3.2 ± 2.1 years). Compared with the control group, the CBS group had a higher incidence of sphenoid sinusitis (81% vs. 52.4%), osteonecrosis (82.9% vs. 51.2%), artery exposure (29.3% vs. 4.9%), and internal carotid artery injury (61% vs. 29.3%). Osteonecrosis and artery exposure were selected as important risk factor for CBS, with p-values of 0.016 and 0.031, respectively. CONCLUSION: CBS is an important factor that affects the survival of patients with NPC. If internal carotid artery injury, artery exposure, sphenoid sinusitis, and osteonecrosis are present, especially the latter two signs, the possibility of CBS should be considered.

2.
J Fluoresc ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457079

RESUMO

This research investigates the use of excitation-emission matrix fluorescence (EEMF) in conjunction with chemometric models to rapidly identify and quantify adulteration in olive oil, a critical concern where sample availability is limited. Adulteration is simulated by blending soybean, peanut, and linseed oils into olive oil, creating diverse adulterated samples. Principal component analysis (PCA) was applied to the EEMF spectral data as an initial exploratory measure to cluster and differentiate adulterated samples. Spatial clustering enabled vivid visualization of the variations and trends in the spectra. The novel application of parallel factor analysis (PARAFAC) for data decomposition in this paper focuses on unraveling correlations between the decomposed components and the actual adulterated components, which offers a novel perspective for accurately quantifying adulteration levels. Additionally, a comparative analysis was conducted between the PCA and PARAFAC methodologies. Our study not only unveils a new avenue for the quantitative analysis of adulterants in olive oil through spectral detection but also highlights the potential for applying these insights in practical, real-world scenarios, thereby enhancing detection capabilities for various edible oil samples. This promises to improve the detection of adulteration across a range of edible oil samples, offering significant contributions to food safety and quality assurance.

3.
Age Ageing ; 53(1)2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38251736

RESUMO

BACKGROUND: Fragmentation of services increases health and social care burden as people live longer with higher prevalence of diseases, frailty and dependency. Local evidence for implementing person-centred integrated care is urgently needed to advance practice and policies to achieve healthy ageing. OBJECTIVE: To test the feasibility and impact of World Health Organization's (WHO) Integrated Care for Older People (ICOPE) approach in China. DESIGN: A randomised controlled trial examining the feasibility of implementing ICOPE approach, evaluating its impact on health outcomes and health resource utilisation. SETTING: Primary care setting in urban and suburban communities of Chaoyang District, Beijing, China. SUBJECTS: Community-dwelling older adults screened as at-risk of functional declines and randomised into intervention (537) and control (1611) groups between September 2020 and February 2021. METHODS: A 6-month intervention program following WHO's ICOPE care pathways implemented by integrated care managers compared to standard available care. RESULTS: After 1 to 1 propensity score matching, participants in intervention and control groups (totally 938) had comparable baseline characteristics, demonstrated feasibility of implementing ICOPE with satisfaction by participants (97-99%) and providers (92-93%). All outcomes showed improvements after a 6-month intervention, while statistically significant least-squares mean differences (control-intervention) in vitality (Mini-Nutritional Assessment Short Form to measure vitality, -0.21, 95% CI, -0.40-0.02), mobility (Short Physical Performance Battery to measure mobility, -0.29, 95% CI, -0.44-0.14) and psychological health (Geriatric Depression Scale five items to measure psychological health, 0.09, 95% CI, 0.03-0.14) were observed (P < 0.05). CONCLUSIONS: It is feasible to localise and implement WHO's ICOPE approach in regions with fragmented resources such as China. Preliminary evidence supports its acceptance among key stakeholders and impact on health outcomes.


Assuntos
Sobrecarga do Cuidador , Prestação Integrada de Cuidados de Saúde , Humanos , Idoso , China/epidemiologia , Organização Mundial da Saúde , Procedimentos Clínicos
4.
Trop Med Int Health ; 28(3): 175-185, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36591905

RESUMO

OBJECTIVE: To comprehensively evaluate the diagnostic efficacy of adenosine deaminase in cerebrospinal fluid (CSF) for tuberculous meningitis (TBM), and the potential influence of patients' age groups and cutoffs of measured adenosine deaminase. METHODS: Systematic review and meta-analysis of relevant studies retrieved from PubMed, Embase, and Web of Science databases. Pooled sensitivity and specificity were calculated with a random-effect model. RESULTS: Overall, 43 studies with 1653 patients with TBM and 3417 controls without were included. Pooled results showed that adenosine deaminase in CSF is associated with satisfactory diagnostic efficacy for TBM, with a pooled sensitivity of 0.86 (95% confidence interval [CI]: 0.82-0.90), specificity of 0.89 (95% CI: 0.86-0.91), positive likelihood ratio of 7.70 (95% CI: 6.16-9.63), and negative likelihood ratio of 0.15 (95% CI: 0.12-0.20). The pooled receiver operating characteristic (AUC) was 0.94 (95% CI: 0.91-0.96), suggesting good performance. Subgroup analyses showed good diagnostic efficacies of adenosine deaminase in CSF for both adults (AUC 0.95) and children (AUC 0.96) with TBM. AUCs indicating the diagnostic accuracies of adenosine deaminase in CSF for TBM were 0.93 for studies with cutoffs <10 U/L and and 0.94 for a cutoff =10 U/L, but only 0.90 for studies with cutoffs >10 U/L. CONCLUSIONS: Measuring adenosine deaminase of CSF shows satisfactory diagnostic efficacy for TBM in children and adults, particularly if using a cutoff ≤10 U/L.


Assuntos
Adenosina Desaminase , Tuberculose Meníngea , Adulto , Criança , Humanos , Adenosina Desaminase/líquido cefalorraquidiano , Líquido Cefalorraquidiano , Curva ROC , Sensibilidade e Especificidade , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/diagnóstico
5.
Inflamm Res ; 72(8): 1745-1760, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37624402

RESUMO

BACKGROUND: As the main effector cells of chronic inflammation and hyperplasia of synovium, fibroblast-like synoviocytes (FLSs) show abnormal proliferation and insufficient apoptosis in the hypoxic microenvironment, which is due to the increase of BNIP3-mediated autophagy. This study aimed to explore the mechanism of geniposide (GE) on hypoxia-induced hyper-proliferative FLSs with a focus on autophagy and the JNK-BNIP3 pathway. METHODS: The dynamic changes of autophagy, apoptosis, and hypoxia-related proteins in adjuvant arthritis (AA) rats were detected by immunohistochemistry and Western blot. The proliferation, autophagy, apoptosis, and mitochondrial state of FLSs were detected by CCK-8, flow cytometry, immunofluorescence, and transmission electron microscopy, respectively. Western blot, qRT-PCR, and co-immunoprecipitation were used to detect the expression of the JNK-BNIP3 pathway. RESULTS: The excessive accumulation of BNIP3 in the synovium of AA rats was accompanied by inhibition of apoptosis and an increase in autophagy. GE inhibited the expression of BNIP3, enhanced apoptosis, decreased autophagy, and improved chronic inflammation and hyperplasia of synovium. The amount of autophagy under different oxygen concentrations was the key to mediating the different survival rates of FLSs, and the inhibition of autophagy triggered apoptosis. GE suppressed the proliferation of FLSs and down-regulated autophagy, leading to the accumulation of ROS and the decrease of mitochondrial membrane potential, induced the increase of apoptosis, and suppressed the accumulation of BNIP3 and the hyperphosphorylation of JNK. CONCLUSION: GE inhibited autophagy by restoring the hypoxia-induced activated JNK-BNIP3 pathway, inducing mitochondrial oxidative damage, augmented apoptosis, and decreased survival rate of FLSs.


Assuntos
Artrite Experimental , Iridoides , Sinoviócitos , Animais , Ratos , Apoptose , Autofagia , Fibroblastos , Hiperplasia , Hipóxia , Inflamação , Proteínas de Membrana , Proteínas Mitocondriais , Iridoides/farmacologia
6.
BMC Public Health ; 23(1): 2127, 2023 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-37904128

RESUMO

BACKGROUND: Nutrition health has become a major public health issue in both high and middle-income countries. Nutrition literacy is an important indicator to evaluate the effect of public health intervention and one of the important concepts in health promotion. Thus, this study aimed to verify the reliability and validity of a nutrition literacy assessment questionnaire (NLAQ) and investigate the associated factors of nutrition literacy among college students. METHODS: We conducted a cross-sectional online survey of college students from April to November 2022 in Wuhan (N = 774). We employed the Cronbach's alpha coefficient, exploratory and confirmatory factor analysis to evaluate the reliability and validity. We used latent profile analysis to classify the nutrition literacy. We conducted Chi-square test and binary logistic regression to identify the influencing factors. RESULTS: The Cronbach's alpha coefficient of the NLAQ and its dimension was ranging from 0.837 to 0.909. The common factors were consistent with the original dimensions. All indicators met the requirements (χ2/df = 6.16 < 8, GFI = 0.929, NFI = 0.939, CFI = 0.948, RMSEA = 0.082 < 0.1). College students' disciplines (χ2 = 7.769, P = 0.021), mothers' education level (χ2 = 26.599, P < 0.001), and fathers' occupation type (χ2 = 11.218, P = 0.024) had impacts on nutrition literacy. CONCLUSION: The NLAQ has good reliability and validity, and could be used as a measurement tool to evaluate college students' nutrition literacy. Schools and families should take targeted measures to improve the college students' nutrition literacy.


Assuntos
Letramento em Saúde , Alfabetização , Humanos , Reprodutibilidade dos Testes , Estudos Transversais , Estudantes , Inquéritos e Questionários , Psicometria/métodos
7.
Sensors (Basel) ; 23(8)2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37112501

RESUMO

In this paper, defect detection and identification in aluminium joints is investigated based on guided wave monitoring. Guided wave testing is first performed on the selected damage feature from experiments, namely, the scattering coefficient, to prove the feasibility of damage identification. A Bayesian framework based on the selected damage feature for damage identification of three-dimensional joints of arbitrary shape and finite size is then presented. This framework accounts for both modelling and experimental uncertainties. A hybrid wave and finite element approach (WFE) is adopted to predict the scattering coefficients numerically corresponding to different size defects in joints. Moreover, the proposed approach leverages a kriging surrogate model in combination with WFE to formulate a prediction equation that links scattering coefficients to defect size. This equation replaces WFE as the forward model in probabilistic inference, resulting in a significant enhancement in computational efficiency. Finally, numerical and experimental case studies are used to validate the damage identification scheme. An investigation into how the location of sensors can impact the identified results is provided as well.

8.
Biochem Biophys Res Commun ; 627: 184-190, 2022 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-36044800

RESUMO

Riboswitches are RNA molecules that can regulate gene expression which is affected by ligand-binding during cotranscriptional folding process. However, the role of ligand during the folding is still unclear. In this study, the pfl domain of Thermosinus carboxydivorans ZTP riboswitch was discussed. The ligand is molecule ZMP. We mainly analyzed the change of ZMP-free and ZMP-bound aptamer domain by the dynamics simulation method. Structural features by calculating their RMSD, RMSF, etc. are analyzed. The results demonstrate that the binding domain require the presence of ZMP to maintain a stable fold. It also suggested that ZMP specificly binding to ZTP can generate more hydrogen bonds in the binding domain. Through the calculation of binding free energy decomposition of each nucleotide, molecule ZMP was found to promote the recognition and binding process of ligands by controlling some special nucleotides in the process of ligand binding. At last, the dynamical correlation and components of conformational motions were both applied to explore the effect of molecule ZMP to ZTP riboswitch. In general, ZMP can effectively affect the motions of the pfl riboswitch and facilitate the folding process of the ZTP riboswitch.These results may provide some new ideas for structural changes in riboswitches and their cotranscriptional folding process.


Assuntos
Aptâmeros de Nucleotídeos , Riboswitch , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/genética , Firmicutes/genética , Ligantes , Simulação de Dinâmica Molecular , Conformação de Ácido Nucleico
9.
Biochem Biophys Res Commun ; 626: 167-174, 2022 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-35994826

RESUMO

Nonalcoholic steatohepatitis (NASH) is the development of non-alcoholic fatty liver disease (NAFLD) and a key element in the exacerbation of NAFLD. Since there are currently no drugs approved by the U.S. Food and Drug Administration to treat this disease, the search for treatments that can be translated into clinical use is urgent. Butyrolactone I (BLI), isolated from Aspergillus terreus, is an active compound possessing multiple biological activities. However, the effects of BLI on NASH have never been reported. In this study, RAW264.7 cells stimulated by lipopolysaccharide (LPS) were applied to study the anti-inflammatory effect and the underlying mechanisms of BLI in vitro. Following this, mice fed with high-fat and -fructose diet (HFFD) were used to explore the alleviation of NASH by BLIin vivo. We found that BLI attenuated inflammation in LPS-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway and downregulating the expression of iNOS and COX-2. Moreover, results of experiments in vivo demonstrated that BLI reduced serum transaminase levels, decreased hepatic fat accumulation, inhibited inflammation, suppressed oxidative stress, and ameliorated liver fibrosis. For the first time, we investigated the role of BLI in the treatment of murine NASH. We found that BLI alleviates NASH partly by inhibiting the NF-κB pathway of signaling. Given its hepatoprotective effects and non-toxic properties, BLI can be a novel and effective drug for NASH patients.


Assuntos
Hepatopatia Gordurosa não Alcoólica , 4-Butirolactona/análogos & derivados , Animais , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Transdução de Sinais
10.
Cell Mol Biol (Noisy-le-grand) ; 67(4): 306-312, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35809275

RESUMO

Pediatric allergic asthma is a chronic disease that affects the lungs and airways. If a child is exposed to certain stimulants such as pollen inhalation, colds, or respiratory infections, the lungs become inflamed and if left untreated can lead to dangerous asthma attacks. One of the most important treatments for this disease is the use of leukotriene modulators, such as montelukast. But recently, due to easier access, cheaper prices and fewer side effects, attention has shifted to non-chemical treatments. Gan-Cao (Glycyrrhizae uralensis), as traditional Chinese medicine, has been proved to have a good therapeutic effect on experimental allergic asthma. But its anti-asthma mechanism is currently unclear. Therefore, the study aimed the comparison between the effect of Gan-Cao and montelukast on the expression of T-bet and GATA-3 genes in children with allergic asthma. For this purpose, fifty children with allergic asthma were divided into two groups. The first group was treated with montelukast for one month. The second group was treated with Gan-Cao root extract. Then the peripheral blood mononuclear cells were isolated, their RNA was extracted, and the relative expression of T-bet and GATA3 transcription factors was evaluated by Real-time PCR. The relationship between them and risk factors for asthma was assessed by relevant statistical tests. The result showed the expression of the GATA3 gene (P = 0.102), T-bet gene (P = 0.888), and the expression ratio of T-bet/GATA-3 genes (P = 0.061) was not significantly different between the two groups. It showed that Gan-Cao can affect the expression of these genes just as much as montelukast. Therefore, this Chinese herb can be used as an alternative or supplement medicine to treat allergic asthma in children.


Assuntos
Asma , Glycyrrhiza uralensis , Acetatos , Asma/tratamento farmacológico , Asma/genética , Asma/metabolismo , Criança , Ciclopropanos , Glycyrrhiza uralensis/metabolismo , Humanos , Leucócitos Mononucleares/metabolismo , Quinolinas , Sulfetos , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo
11.
Water Sci Technol ; 85(9): 2443-2462, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35576247

RESUMO

Structured biochar (SC) was prepared by biochar from cattail-sludge mixture (CS) and high-density polyethylene (HDPE) and treated as an adsorbent, and the KH2PO4 and NH4Cl solution were treated as adsorbates, to explore the adsorption capacity of phosphorus (P) and nitrogen (N) on SC in water. A single factor experimental method was employed to determine the optimal parameters for SC. The results showed that: 60% sizing amount, 5 N (cm2)-1 molding pressure, 160 °C molding temperature and 95 min molding time were optimal parameters for SC preparation. The adsorption of P and N on SC conforms to the Langmuir model, with the distribution of adsorption sites on the surface tending to be even. The adsorption of P and N on SC is favorable and spontaneous, and the adsorption tends to be monolayer adsorption with a major role for chemical adsorption. The higher the temperature, the higher the adsorption capacity of P and N on SC is, and the affinity of SC with P is higher than that with N. The pseudo-second-order kinetic model for the adsorption of N and P by SC has a high degree of fit. The pHpzc value of SC was 8.57. The hydrophobicity and stability of SC are rather high, with the surface particles closely bonded and increased roughness and pore diameter. The adsorption mechanism of P and N on SC can be attributed to pore filling, electrostatic attraction and hydrogen bonding. The results can provide a new technology for the resource utilization of cattails and sludge, a new idea for the recycling and reuse of biochar, and a basis for the selection of materials for the treatment of eutrophic water bodies.


Assuntos
Esgotos , Poluentes Químicos da Água , Adsorção , Carvão Vegetal , Cinética , Água , Poluentes Químicos da Água/análise
12.
Am J Otolaryngol ; 42(6): 103149, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34242882

RESUMO

OBJECTIVE: The association between benign paroxysmal positional vertigo (BPPV) and impaired calcium metabolism has attracted widespread interest. Several studies have suggested that decreased bone mineral density (BMD) and serum 25-hydroxyvitamin D (25(OH)D) level are related to the occurrence and/or recurrence of BPPV; however, the characteristics of bone metabolism in patients with BPPV subtypes have not been fully investigated, and conclusions have been controversial. This study aimed to evaluate BMD and serum levels of 25(OH)D and bone turnover markers to clarify the characteristics of bone metabolism in patients with different types of BPPV. METHOD: We retrospectively analysed the data of new-onset idiopathic postmenopausal female patients with BPPV at our institution from January 2016 to January 2020. The patients' demographic data including age, medication history, concomitant diseases, onset time, clinical form, laboratory indicators, such as serum levels of 25(OH)D, bone formation markers, namely, amino-terminal propeptide of type I procollagen (PINP) and osteocalcin (OC), bone resorption marker, namely, ß-isomerized carboxy-terminal telopeptide of type I collagen (ß-CTX), and BMD were collected and analysed. RESULTS: This study included 201 consecutive postmenopausal female patients with BPPV. Among them, 138 were diagnosed with posterior semicircular canal BPPV, 42 were diagnosed with lateral semicircular canal canalolithiasis, and 21 were diagnosed with lateral semicircular canal cupulolithiasis. There were no significant differences in age distribution, body mass index, clinical history, levels of albumin, globulin, uric acid, creatinine, or blood urea nitrogen, lipid profiles (except high-density lipoprotein cholesterol) and routine blood parameters among these groups (P > 0.05). There were no significant differences in the mean T-score and BMD values of different sites or in the serum levels of 25(OH)D and bone turnover markers (PINP, OC and ß-CTX) among the subgroups (P > 0.05). The proportion of reduction in BMD (T-score < -1 SD) and decreased serum vitamin D level (< 20 ng/ml) were not significantly different between the subgroups (P > 0.05). CONCLUSION: There were no significant differences in bone metabolism in postmenopausal female patients with different types of idiopathic BPPV.


Assuntos
Vertigem Posicional Paroxística Benigna/metabolismo , Osso e Ossos/metabolismo , Pós-Menopausa/metabolismo , Vertigem Posicional Paroxística Benigna/classificação , Biomarcadores/metabolismo , Densidade Óssea , Reabsorção Óssea , Cálcio/metabolismo , Colágeno Tipo I/metabolismo , Feminino , Humanos , Osteocalcina/metabolismo , Osteogênese , Fragmentos de Peptídeos/metabolismo , Peptídeos/metabolismo , Pró-Colágeno/metabolismo , Recidiva , Estudos Retrospectivos , Vitamina D/análogos & derivados , Vitamina D/sangue
13.
Yi Chuan ; 43(3): 280-288, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33724212

RESUMO

To improve the transfection efficiency of chicken primordial germ cells (PGCs), the present study evaluated the plasmid dosage and cell number on the efficiencies of three transfection reagents (Lipofectamine 2000, 3000 and LTX & Plus Reagent). PGCs was isolated from embryonic gonads of Huiyang bearded chicken. After 60 days of culture in vitro, the cells were transfected by using Lipofectamine transfection reagents with piggyBac vectors coding for the green fluorescence protein (GFP). PGCs were passaged in culture and fluorescent cells were screened and selected by flow cytometry at three days after transfection. At three weeks post transfection, about 2000 cells were injected into the stage 16 Hamburger and Hamilton (HH) embryos and incubated until stage 30 HH. The results showed that Lipofectamine 3000 was the best for transfection of PGCs. The highest transfection efficiency of PGCs could be achieved with a combination of 3 µg plasmid, 4 µL Lipofectamine 3000 transfection reagent and 0.5×10 4PGCs cells. Flow cytometry analysis showed a 23.4% efficiency of stable transfection of PGCs using Lipofectamine 3000 with piggyBac vector, which was improved 2 times or more over current commonly used methods. After reinjecting PGCs into recipient chicken embryos, GFP-positive cells were observed in the gonads of the recipient chicken embryo by fluorescence microscopy. The study comprehensively evaluated the factors of transfection reagents, plasmid dosage and cell number to optimize the transfection of PGCs, thereby providing a foundation for the efficient preparation of transgenic and gene-edited chickens.


Assuntos
Galinhas , Células Germinativas , Animais , Animais Geneticamente Modificados , Embrião de Galinha , Galinhas/genética , Gônadas , Transfecção
14.
Mol Cancer ; 19(1): 111, 2020 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-32593305

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

15.
J Hepatol ; 72(4): 761-773, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31837357

RESUMO

BACKGROUND & AIMS: Mucin 13 (MUC13) is reportedly overexpressed in human malignancies. However, the clinicopathological and biological significance of MUC13 in human intrahepatic cholangiocarcinoma (iCCA) remain unclear. The aim of this study was to define the role of MUC13 in the progression of iCCA. METHODS: Expression levels of MUC13 in human iCCA samples were evaluated by immunohistochemistry, western blot, and real-time PCR. In vitro and in vivo experiments were used to assess the effect of MUC13 on iCCA cell growth and metastasis. Crosstalk between MUC13 and EGFR/PI3K/AKT signaling was analyzed by molecular methods. The upstream regulatory effects of MUC13 were evaluated by Luciferase and DNA methylation assays. RESULTS: MUC13 was overexpressed in human iCCA specimens and iCCA cells. MUC13 overexpression positively correlated with clinicopathological characteristics of iCCA, such as vascular invasion and lymph node metastasis, and was independently associated with poor survival. Results from loss-of-function and gain-of-function experiments suggested that knockdown of MUC13 attenuated, while overexpression of MUC13 enhanced, the proliferation, motility, and invasiveness of iCCA cells in vitro and in vivo. Mechanistically, we found that the phosphatidylinositol 3-kinase-AKT signal pathway and its downstream effectors, such as tissue inhibitor of metalloproteinases 1 and matrix metallopeptidase 9, were required for MUC13-mediated tumor metastasis of iCCA. MUC13 interacted with epidermal growth factor receptor (EGFR) and subsequently activated the EGFR/PI3K/AKT signaling pathway by promoting EGFR dimerization and preventing EGFR internalization. We also found that MUC13 was directly regulated by miR-212-3p, whose downregulation was related to aberrant CpG hypermethylation in the promoter area. CONCLUSIONS: These findings suggest that aberrant hypermethylation-induced downregulation of miR-212-3p results in overexpression of MUC13 in iCCA, leading to metastasis via activation of the EGFR/PI3K/AKT signaling pathway. LAY SUMMARY: Mucin 13 overexpression has been implicated in the development of malignancies, although its role in intrahepatic cholangiocarcinoma has not been studied. Herein, we show that mucin 13 plays a critical role in intrahepatic cholangiocarcinoma. Mucin 13 could have therapeutic value both as a prognostic marker and as a treatment target.


Assuntos
Neoplasias dos Ductos Biliares/metabolismo , Colangiocarcinoma/metabolismo , Progressão da Doença , Mucinas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética , Animais , Neoplasias dos Ductos Biliares/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Colangiocarcinoma/patologia , Receptores ErbB/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Mucinas/genética , Estudos Retrospectivos , Transfecção , Carga Tumoral/genética , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
16.
BMC Endocr Disord ; 20(1): 43, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245458

RESUMO

BACKGROUND: An accurate diagnosis for high-suspicion nodules based on the 2015 American Thyroid Association (ATA) guidelines would reduce unnecessary invasive examinations. Elastography is a useful tool for discriminating benign and malignant thyroid nodules. The aim of this study is to investigate the diagnostic efficiency of elastography for high-suspicion thyroid nodules based on the 2015 ATA guidelines in the Chinese population. METHODS: Thyroid nodules with high-suspicion characteristics based on the 2015 ATA guidelines were subjected to conventional ultrasound (US) and ultrasound strain elastography (USE) examinations at 12 hospitals from 4 geographic regions across China. Cytology/histology of thyroid nodules was used as a reference method. Receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic performance of the elasticity score (ES) and strain ratio (SR). Logistic regression analysis was used to determine the predictors of malignancy. RESULTS: Overall, a total of 1445 thyroid nodules (834 malignant, 611 benign) from 12 centers were included in the final analysis. The areas under the curve of the ES and SR were 0.828 and 0.732, respectively. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the ES were 92.4, 60.7, 79.0, 76.3 and 85.5%, respectively, and those of the SR were 81.1, 50.1, 68.9, 65.9 and 67.9%, respectively. The combination of the Thyroid Imaging Reporting and Data System (TI-RADS) and ES led to a significant increase in the sensitivity and NPV (97.1 and 91.9%, respectively) compared with the TI-RADS alone. Logistic regression analysis showed that microcalcifications (OR = 5.290), taller than wide (OR = 12.710), irregular margins (OR = 10.117), extrathyroidal extension (ETE; OR = 6.412), the ES (OR = 3.741) and the SR (OR = 1.083) were independent predictors of malignant thyroid nodules. The sensitivity, specificity, accuracy, PPV and NPV of the ES were all superior in nodules ≥1 cm than in those < 1 cm (95.0% vs 90.4, 68.8% vs 56.8, 85.9% vs 74.4, 85.2% vs 69.9, and 87.8% vs 84.2%, respectively). CONCLUSIONS: Elastography combined with the ES is a valuable tool for the assessment of high-suspicion thyroid nodules based on the 2015 ATA guidelines, especially in nodules ≥1 cm.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Guias de Prática Clínica como Assunto/normas , Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/diagnóstico , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/diagnóstico por imagem
17.
Zhongguo Zhong Yao Za Zhi ; 45(21): 5193-5199, 2020 Nov.
Artigo em Zh | MEDLINE | ID: mdl-33350235

RESUMO

Based on the previous study of compound liquorice microemulsion, this paper aims to prepare the compound liquorice microemulsion gel and investigate its pharmacodynamics of chronic eczema. The type, dosage and adding method of gel matrix, and formula dosage of humectant were optimized by single factor method to obtain the formula and preparation technique of the gel. With glycyrrhizic acid, glycyrrhetin and oxymatrine used as evaluation indexes, the Franz diffusion cell method was adopted to monitor the in vitro release profile of the gel. Eczema model of delayed-type hypersensitivity in mice was chosen to detect the ear swelling rate, degree of inflammatory cell infiltration of ear pieces, and pathological changes of ear pieces, so as to investigate the therapeutic effect of the microemulsion gel. The preparation process of the compound liquorice microemulsion gel was stable. The release of glycyrrhizin and oxymatrine was most consistent with the Hixcon-Crowell kinetic model, while the release of glycyrrhizic acid was most consistent with the Ritger-Peppas kinetic model. The pharmacodynamics studies proved that compound liquorice microemulsion gel could significantly reduce the ear swelling rate in mice, with good anti-inflammatory effect as well as the ability to resist the pathological changes of chronic eczema and inhibit the infiltration of dermal inflammatory cells. Therefore, the preparation process of compound liquorice microemulsion gel is feasible, with stable drug release and a significant therapeutic effect on chronic eczema.


Assuntos
Glycyrrhiza , Administração Cutânea , Animais , Liberação Controlada de Fármacos , Emulsões , Géis , Camundongos , Absorção Cutânea
18.
BMC Genomics ; 20(1): 323, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035925

RESUMO

BACKGROUND: Artificial induction of mutagenesis is effective for genetic resource innovation and breeding. However, the traditional mutation methods for fish breeding are not convenient or safe for daily use. Hence, development of a simple, safe and effective mutagenesis method with a high mutation rate and applicability to multiple fish species, is needed. RESULTS: We reported the first successful mutagenesis in a marine aquaculture fish species, Japanese flounder, Paralichthys olivaceus, using a novel atmosphere and room temperature plasma (ARTP) mutagenesis tool. ARTP treatment time was optimized for the fertilized eggs and sperm, respectively. Eggs fertilized for 60 min were treated by ARTP with a radio-frequency power input of 120 W, and the ARTP treatment time was 25 min. Under an ARTP radio-frequency power input of 200 W, the optimal treatment time for sperm diluted with Ringer's solution by 1:40 v/v was 10 min. The ARTP-treated group presented differences in morphological traits such as body height, total length among individuals at day 90 after hatching. Whole-genome sequencing was used to reveal the mutation features of ARTP-treated individuals collected at day 120 after hatching. In total, 69.25Gb clean data were obtained from three controls and eight randomly selected ARTP-treated individuals, revealing 240,722 to 322,978 SNPs and 82,149 to 86,798 InDels located in 17,394~18,457 and 12,907~13,333 genes, respectively. The average mutation rate reached 0.064% at the genome level. Gene ontology clustering indicated that genes associated with cell components, binding function, catalytic activity, cellular process, metabolic process and biological regulation processes had higher mutation rates. CONCLUSIONS: ARTP mutagenesis is a useful method for breeding of fish species to accelerate the selection of economically important traits that would benefit the aquaculture industry, given the variety of mutations detected.


Assuntos
Linguado/genética , Gases em Plasma , Ondas de Rádio , Animais , Tamanho Corporal , Cruzamento , Análise por Conglomerados , Linguado/crescimento & desenvolvimento , Mutação INDEL , Japão , Masculino , Mutagênese , Polimorfismo de Nucleotídeo Único , Espermatozoides/efeitos da radiação , Temperatura , Sequenciamento Completo do Genoma , Zigoto/efeitos da radiação
19.
Invest New Drugs ; 37(4): 784-790, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30740631

RESUMO

Liver cancer is a kind of high mortality cancer due to the difficulty of early diagnosis. It is necessary to develop the anticancer agents to treat liver cancer. Here, a novel chalcone derivative was synthesized and evaluated for anticancer activity in vitro against liver cancer cell lines (HepG2, SNU-423, SMMC7221, and SNU-398). The chalcone hybrid 9 displayed the antiproliferative effect against HepG2, SNU-423, SMMC7221 and SNU-398 cells with IC50 values of 0.9 µM, 2.7 µM, 6.2 µM and 4.6 µM, respectively. Cellular mechanisms showed that derivative 9 could obviously inhibit HepG2 cells growth and colony formation in a concentration-dependent manner. Analogue 9 inhibited the migration by regulating the expression levels of migration-releated markers and transcription factors (Snail and Slug). Tubulin polymerization inhibition assay illustrated that chalcone hybrid 9 might be a potent tubulin polymerization inhibitor. Importantly, compound 9 displayed the antitumor activity against liver cancer HepG2 cells in vivo with the low toxicity toward mice. Therefore, compound 9 as a novel tubulin polymerization inhibitor deserves further investigation to treat liver cancer. Graphical abstract Compound 9 displayed the antitumor activity against liver cancer HepG2 cells in vivo and low toxicity toward mice Figure: Orally antitumor chalcone hybrid 9 inhibited HepG2 cells growth and migration as the tubulin binding agent.


Assuntos
Antineoplásicos/farmacologia , Chalconas/farmacologia , Moduladores de Tubulina/farmacologia , Administração Oral , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Camundongos Nus , Tubulina (Proteína)/metabolismo
20.
Biomed Chromatogr ; 33(7): e4526, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30834567

RESUMO

Geniposide (GE) is an iridoid glycoside compound with anti-inflammatory effect. The potential of sphingosine 1-phosphate (S1P) as a plasma marker in human diseases was suggested recently in the literature, which demonstrated that, in patients with inflammatory diseases, plasma S1P was elevated. It follows that the obstructive coronary artery disease can be predicted with serum S1P. Therefore, S1P can also be potentially used as a pharmacodynamic marker to study adjuvant arthritis (AA) rats. In the current study, a UHPLC-MS/MS method combined with the microdialysis sampling technique (using FTY720 phosphate as an internal standard) was adopted and validated to measure S1P levels in the hemodialysis fluid and joint cavity dialysates of AA rats after oral administration of GE. A S1P concentration-time curve in the dialysate was established in this study. It was demonstrated that GE exerted an anti-inflammatory effect by reducing AA-induced elevated S1P levels. It is showed that changes in S1P concentrations over time can be used to monitor the pharmacodynamic effects of GE in treating AA rats in pharmacodynamic studies.


Assuntos
Artrite Experimental/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Iridoides/farmacocinética , Lisofosfolipídeos/análise , Esfingosina/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Animais , Estabilidade de Medicamentos , Iridoides/análise , Iridoides/química , Modelos Lineares , Masculino , Microdiálise , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Esfingosina/análise
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