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1.
Exp Neurol ; 377: 114794, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38685307

RESUMO

BACKGROUND: Interleukin-1 receptor-associated kinase 4 (IRAK4) plays an important role in immune modulation in various central nervous system disorders. However, IRAK4 has not been reported in epilepsy models in animal and clinical studies, nor has its involvement in regulating pyroptosis in epilepsy. METHOD: First, we performed transcriptome sequencing, quantitative real-time polymerase chain reaction, and western blot analysis on the hippocampal tissues of refractory epilepsy patients to measure the mRNA and protein levels of IRAK4 and pyroptosis-related proteins. Second, we successfully established a pentylenetetrazol (PTZ)-induced seizure mouse model. We conducted behavioral tests, electroencephalography, virus injection, and molecular biology experiments to investigate the role of IRAK4 in seizure activity regulation. RESULTS: IRAK4 is upregulated in the hippocampus of epilepsy patients and PTZ-induced seizure model mice. IRAK4 expression is observed in the hilar neurons of PTZ-induced mice. Knocking down IRAK4 in PTZ-induced mice downregulated pyroptosis-related protein expression and alleviated seizure activity. Overexpressing IRAK4 in naive mice upregulated pyroptosis-related protein expression and increased PTZ-induced abnormal neuronal discharges. IRAK4 and NF-κB were found to bind to each other in patient hippocampal tissue samples. Pyrrolidine dithiocarbamate reversed the pyroptosis-related protein expression increase caused by PTZ. PF-06650833 alleviated seizure activity and inhibited pyroptosis in PTZ-induced seizure mice. CONCLUSION: IRAK4 plays a key role in the pathological process of epilepsy, and its potential mechanism may be related to pyroptosis mediated by the NF-κB/NLRP3 signaling pathway. PF-06650833 has potential as a therapeutic agent for alleviating epilepsy.

2.
Epilepsy Res ; 201: 107315, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38364765

RESUMO

PURPOSE: Epilepsy is a debilitating disease that can lead to series of social and psychological issues, impairing the quality of life of people with epilepsy (PWE). This survey aimed to investigate the awareness, attitudes, and first-aid knowledge of epilepsy in university students METHOD: This cross-sectional study was conducted in Henan Province, China between January 1 and April 30, 2022. Students majored in education, medicine, science and engineering from 8 universities attended the study. The survey questionnaire comprised 28 questions covering 4 sections: demographic characteristics, awareness of epilepsy, attitudes toward PWE and knowledge of first aid for seizures. RESULTS: A total of 2376 university students completed the questionnaire. 94.7% heard of epilepsy. In the first aid knowledge section, individual question was correctly answered by at least 50% students, 9.3% students correctly answered all questions. Attitude toward PWE was independently (R2 =0.108, F=73.227, p < 0.001) associated with both awareness of epilepsy (B=0.411, p < 0.001) and first aid knowledge of epilepsy (B=0.047, p = 0.001). Among the three majors, medical students had more positive attitudes toward PWE than students majored in education, science and engineering (p < 0.05). However, medical students performed worse among the groups when answering the first aid knowledge questions. CONCLUSION: This survey showed that university students in Central China had a good awareness of epilepsy. For medical students, improvements are necessary for the awareness of the first aid knowledge for seizure.


Assuntos
Epilepsia , Primeiros Socorros , Humanos , Estudos Transversais , Universidades , Qualidade de Vida , Conhecimentos, Atitudes e Prática em Saúde , Epilepsia/terapia , Epilepsia/psicologia , Convulsões , Estudantes/psicologia , Inquéritos e Questionários , China
3.
Int J Food Microbiol ; 414: 110574, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38325259

RESUMO

The proliferation of antimicrobial-resistant microbes and resistance genes in various foods poses a serious hazard to public health. The plasmid-mediated tigecycline resistance gene tet(X4) has been detected in Enterobacterales from various niches but has not yet been reported in eggs. This study aimed to investigate the occurrence and characteristics of tigecycline-resistant strains from retail eggs. A total of 144 eggs were purchased from farmers' markets in Guangdong province, China, and eggshell (n = 144) and egg content (n = 96) samples were used to screen for tigecycline-resistant strains. Eight Escherichia coli strains (two ST195, one ST48, ST8165, ST752, ST93, ST189, and ST224) and one Klebsiella pneumoniae strain (ST252) recovered from eight (5.56 %, 8/144) egg samples (eggshells, n = 6; egg content, n = 2) were positive for tet(X4). Notably, the two E. coli ST195 strains were closely (15-54 SNPs) related to all the tet(X4)-positive E. coli ST195 from various origins (food animals, foods, migratory birds, human, and environment) deposited in GenBank. The E. coli ST224 showed a close phylogenetic relationship (9-12 SNPs) with two tet(X4)-positive E. coli strains from chicken feces and retail chicken in Guangdong province. The hybrid plasmid IncFIA(HI1)-HI1A-HI1B(R27) constitutes the predominant tet(X4) vector both herein (7/9, 77.78 %) and in the GenBank database (32/160, 20 %). The tet(X4)-positive IncFIA(HI1)-HI1A-HI1B(R27) plasmids, sharing highly similar structures, have been widely disseminated across China. However, the IncFIA(HI1)-HI1A-HI1B(R27) plasmids exhibit poor stability and low conjugation frequency. The contamination of tet(X4)-positive bacteria internally and externally in retail eggs poses a prospective food safety threat. More attention should be paid to the spread of the tet(X4) gene via epidemic clone E. coli ST195 and the plasmid IncFIA(HI1)-HI1A-HI1B(R27).


Assuntos
Ovos , Escherichia coli , Animais , Humanos , Escherichia coli/genética , Filogenia , Tigeciclina , Galinhas , Plasmídeos/genética , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana
4.
Cell Oncol (Dordr) ; 47(1): 157-174, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37632669

RESUMO

PURPOSE: Ovarian cancer (OC) is the leading cause of death from gynecological malignancies, and its etiology and pathogenesis are currently unclear. Recent studies have found that PUF60 overexpressed in various cancers. However, the exact function of PUF60 in global RNA processing and its role in OC has been unclear. METHODS: The expression of PUF60 and its relationship with clinical characteristics were analyzed by multiple database analysis and immunohistochemistry. Phenotypic effects of PUF60 on ovarian cancer cell proliferation and metastasis were examined by in vitro cell proliferation assay, migration assay, and in vivo xenograft models and lung metastasis models. RNA immunoprecipitation, seahorse analyses, RNA stability assay were used to study the effect of PUF60 on the stability of oxidative phosphorylation (OXPHOS)-related genes in OC. RESULTS: We report PUF60 is highly expressed in OC with frequent amplification of up to 33.9% and its upregulation predicts a poor prognosis. PUF60 promotes the proliferation and migration of OC cells both in vitro and in vivo. Mechanistically, we demonstrated that silencing of PUF60 enhanced the stability of mRNA transcripts involved in OXPHOS and decreased the formation of processing bodies (P-bodies), ultimately elevating the OXPHOS level. CONCLUSION: Our study unveils a novel function of PUF60 in OC energy metabolism. Thus, PUF60 may serve as a novel target for the treatment of patients with OC.


Assuntos
Neoplasias Ovarianas , Fosforilação Oxidativa , Feminino , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Regulação para Cima
5.
Microbiol Spectr ; 11(3): e0076723, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37067462

RESUMO

Several variants of the plasmid-carried tigecycline resistance gene cluster, tmexCD-toprJ, have been identified. This study characterized another novel variant, tmexC6D6-toprJ1b, located on the chromosome of environmental-origin Pseudomonas mendocina. TMexC6D6-TOprJ1 mediates resistance to multiple drugs, including tigecycline. The promoter activity of tmexC6D6-toprJ1b and negative transcriptional repression by the upstream regulator tnfxB6 are crucial for the expression of tmexC6D6-toprJ1b. tmexC6D6-toprJ1b was found in the plasmids or chromosomes of different Pseudomonas species from six countries. Two genetic backgrounds, class 1 integrons and int-carrying integrase units, were found adjacent to the tmexC6D6-toprJ1b gene cluster and might mediate the transfer of this novel efflux pump gene cluster in Pseudomonas. Further phylogenetic analysis revealed Pseudomonas as the major reservoir of tmexCD-toprJ variants, warranting closer monitoring in the future. IMPORTANCE Tigecycline is one of the treatment options for serious infections caused by multidrug-resistant bacteria, and tigecycline resistance has gained extensive attention. The emergence of a transferable tigecycline resistance efflux pump gene cluster, tmexCD-toprJ, severely challenged the efficiency of tigecycline. In this study, we identified another novel tmexCD-toprJ variant, tmexC6D6-toprJ1b, which could confer resistance to multiple classes of antibiotics, including tigecycline. Although tmexC6D6-toprJ1b was found only in Pseudomonas species, tmexC6D6-toprJ1b might spread to Enterobacteriaceae hosts via mobile genetic elements resembling those of other tmexCD-toprJ variants, compromising the therapeutic strategies. Meanwhile, novel transferable tmexCD-toprJ variants are constantly emerging and mostly exist in Pseudomonas spp., indicating Pseudomonas as the important hidden reservoir and origin of tmexCD-toprJ variants. Continuous monitoring and investigations of tmexCD-toprJ are urgent to control its spread.


Assuntos
Antibacterianos , Pseudomonas , Tigeciclina/farmacologia , Pseudomonas/genética , Pseudomonas/metabolismo , Filogenia , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Plasmídeos , Testes de Sensibilidade Microbiana
6.
Environ Res ; 217: 114913, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36427633

RESUMO

To address the drinking safety problems associated with high arsenic(III) (As(III)) and bacteria in underground water, core-shell Fe-Ag@AgCl nanowires were synthesized and exhibited excellent photocatalytic oxidation effects on co-existing As(III) and Escherichia coli (E. coli). With the introduction of Fe, the nanowires that were used 5 times could be easily magnetically collected, and the As(III) oxidation effect of these re-chlorinated nanowires increased from 39% to 60%. E. coli was completely inactivated within 60 min without photoreactivation after 20 min. Extracellular polymeric substances have play a protective role in the disinfection process. Quenching testing results confirmed that, except for the superoxide radical (•O2-), the subdominant active species were different for different objects: hole (hVB+) to As(III) and hydroxyl radical (•OH) to E. coli. Therefore the system with co-existing As(III) and E. coli, the inactivation effect of Fe-Ag@AgCl on E. coli decreased remarkably with an increase in As(III) concentration, while the oxidation process of As(III) was not significantly affected by E. coli until E. coli was increased to 108 cfu/mL. The photocatalytic process of co-existing As(III) and E. coli is displayed in a schematic diagram and was tested using desired results obtained from field groundwater in Xiantao City, Hubei Province. The function of Fe in band structures and density of states was analyzed using plane-wave density functional theory. These magnetic nanowires presented excellent photocatalytic ability on co-existing As(III) and E. coli, and provided new insights into drinking water safety in high-arsenic areas.


Assuntos
Arsênio , Escherichia coli , Luz , Arsênio/farmacologia , Oxirredução , Desinfecção/métodos , Catálise
7.
IEEE J Biomed Health Inform ; 26(8): 4067-4078, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35503848

RESUMO

Clinical workflow of cardiac assessment on 2D echocardiography requires both accurate segmentation and quantification of the Left Ventricle (LV) from paired apical 4-chamber and 2-chamber. Moreover, uncertainty estimation is significant in clinically understanding the performance of a model. However, current research on 2D echocardiography ignores this vital task while joint segmentation with quantification, hence motivating the need for a unified optimization method. In this paper, we propose a multitask model with Task Relation Spatial co-Attention (referred as TRSA-Net) for joint segmentation, quantification, and uncertainty estimation on paired 2D echo. TRSA-Net achieves multitask joint learning by novelly exploring the spatial correlation between tasks. The task relation spatial co-attention learns the spatial mapping among task-specific features by non-local and co-excitation, which forcibly joints embedded spatial information in the segmentation and quantification. The Boundary-aware Structure Consistency (BSC) and Joint Indices Constraint (JIC) are integrated into the multitask learning optimization objective to guide the learning of segmentation and quantification paths. The BSC creatively promotes structural similarity of predictions, and JIC explores the internal relationship between three quantitative indices. We validate the efficacy of our TRSA-Net on the public CAMUS dataset. Extensive comparison and ablation experiments show that our approach can achieve competitive segmentation performance and highly accurate results on quantification.


Assuntos
Ecocardiografia , Ventrículos do Coração , Atenção , Ventrículos do Coração/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Tórax , Incerteza
8.
Polymers (Basel) ; 14(7)2022 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-35406234

RESUMO

As a new type of energetic material, reactive materials are widely used at present; in particular, the metal/polymer mixtures type reactive materials show great advantages in engineering applications. This type of reactive material has good mechanical properties, and its overall performance is insensitive and high-energy under external impact loading. After a large number of previous studies, our team found that the energy release characteristics of PTFE/Al/Si reactive material are prominent. In order to master the mechanical properties of PTFE/Al/Si reactive materials, the quasi-static mechanical properties and dynamic mechanical properties were obtained by carrying out a quasi-static compression test and a dynamic SHPB test in this paper. Based on the experimental data, a Johnson-Cook constitutive model of PTFE/Al/Si reactive material considering strain hardening effect, strain rate hardening effect and thermal softening effect was constructed. The relevant research results will be used to guide future research on the reaction mechanism of PTFE/Al/Si reactive materials, in order to promote the engineering application of PTFE/Al/Si reactive materials.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35167446

RESUMO

Segmentation of the left ventricular (LV) myocardium in 2-D echocardiography is essential for clinical decision making, especially in geometry measurement and index computation. However, segmenting the myocardium is a time-consuming process and challenging due to the fuzzy boundary caused by the low image quality. The ground-truth label is employed as pixel-level class associations or shape regulation in segmentation, which works limit for effective feature enhancement for 2-D echocardiography. We propose a training strategy named multiconstrained aggregate learning (referred to as MCAL), which leverages anatomical knowledge learned through ground-truth labels to infer segmented parts and discriminate boundary pixels. The new framework encourages the model to focus on the features in accordance with the learned anatomical representations, and the training objectives incorporate a boundary distance transform weight (BDTW) to enforce a higher weight value on the boundary region, which helps to improve the segmentation accuracy. The proposed method is built as an end-to-end framework with a top-down, bottom-up architecture with skip convolution fusion blocks and carried out on two datasets (our dataset and the public CAMUS dataset). The comparison study shows that the proposed network outperforms the other segmentation baseline models, indicating that our method is beneficial for boundary pixels discrimination in segmentation.


Assuntos
Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Ecocardiografia , Ventrículos do Coração/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Miocárdio
10.
Dalton Trans ; 51(11): 4377-4385, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35191915

RESUMO

The synthesis of three N-heterocyclic carbene complexes by stepwise grinding is described in this paper. The benzimidazolium salts ([H2L]Br2 and [H2L](PF6)2 ([H2L] = 1,1'-di(2-picolyl)-3,3'-methylenedibenzoimidazolium)) were initially prepared. Their reactions with Ni(OAc)2·4H2O by grinding afforded three nickel complexes, [NiL]Br2·CH3OH (1), [NiL]Br2·2H2O (1') and [NiL](PF6)2·0.5CH3CN (2), respectively. A five-coordinated complex [NiLBr]PF6 (3) was further obtained by grinding NH4PF6 with complex 1 or 1', or grinding KBr with complex 2. Complex 3 can also be obtained by direct grinding of complexes 1/1' and 2. Complex 3 was subsequently used as a catalyst in the C-S bond cross-coupling of 2-bromoacetophenone and 2-mercaptobenzothiazole. The entire procedure from the synthesis to the catalytic reaction was performed by mechanochemistry. The green metrics E-factor and EcoScale close to ideal values showed the eco-friendly nature of the entire procedure.

11.
Front Oncol ; 11: 732058, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490127

RESUMO

OBJECTIVE: Ovarian cancer (OV) is the most fatal and frequent type of gynecological malignancy worldwide. TIMELESS (TIM), as a circadian clock gene, has been found to be highly expressed and predictive of poor prognosis in various cancers. However, the function of TIM in OV is not known. This study was designed to investigate the biological functions and underlying mechanisms of TIM during OV progression. METHODS: Cell viability assay, cell migration assay, immunohistochemistry staining, qPCR analyses, and tumor xenograft model were used to identify the functions of TIM in OV. Bioinformatics analyses, including GEPIA, cBioPortal, GeneMANIA, and TIMER, were used to analyze the gene expression, genetic alteration, and immune cell infiltration of TIM in OV. RESULTS: TIM is highly expressed in OV patients. TIM knockdown inhibited OV cell proliferation, migration, and invasion both in vitro and in vivo. Genetic alteration of TIM was identified in patients with OV. TIM co-expression network indicates that TIM had a wide effect on the immune cell infiltration and activation in OV. Further analysis and experimental verification revealed that TIM was positively correlated with macrophages infiltration in OV. CONCLUSIONS: Our study unveiled a novel function of highly expressed TIM associated with immune cell especially macrophages infiltration in OV. TIM may serve as a potential prognostic biomarker and immunotherapy target for OV patients.

12.
J Comput Assist Tomogr ; 45(6): 837-842, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34347709

RESUMO

OBJECTIVE: The aim of this study was to investigate whether the texture features of lung computed tomography images were altered by primary breast cancer without pulmonary metastasis. METHODS: Texture analysis was performed on the regions of interest of lung computed tomography images from 36 patients with breast cancer and 36 healthy controls. Texture parameters between subjects with different clinical stages and hormone receptor (HR) statuses in patients with breast cancer were analyzed. RESULTS: Three texture parameters (mean, SD, and variance) were significantly different between patients with breast cancer and healthy controls and between preoperative and postoperative stages in patients with breast cancer. All 3 parameters showed an increasing trend under the tumor-bearing state. These parameters were significantly higher in the stage III + IV group than in the stage I + II group. The variance parameter was significantly higher in the HR-negative group than in the HR-positive group. CONCLUSIONS: Texture analysis may serve as a novel additional tool for discovering conventionally invisible changes in the lung tissue of patients with breast cancer.


Assuntos
Neoplasias da Mama/patologia , Pulmão/anatomia & histologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Math Biosci Eng ; 18(4): 3667-3679, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-34198405

RESUMO

The medical image management and analysis system proposed in this paper is a medical software developed by the Browser/Server (B/S) architecture after investigating the workflow of the relevant departments of the hospital, which realizes the entire process of patients from consultation to printing of reports. The computer-aided diagnosis function is added based on image management. Due to the difficulty in collecting medical image data, in the computer-aided diagnosis module, this paper only uses the common fungal keratitis collected from the hospital in the laboratory. Focused microscope images are used for experiments. First, the images were trained with three convolutional neural networks, AlexNet, ZFNet, and VGG16. These models which classify fungal keratitis were obtained and integrated was performed to obtain better classification results. Finally, the model was integrated with the system designed in this paper, which realized the automatic diagnosis of Confocal Microscopy (CM) images of fungal keratitis online and provided it to medical staff for reference. The system can improve the work efficiency of the image-related departments while reducing the workload of doctors in the department to manually read the films.


Assuntos
Processamento de Imagem Assistida por Computador , Ceratite , Diagnóstico por Computador , Humanos , Ceratite/diagnóstico por imagem , Redes Neurais de Computação , Software
14.
Int Immunopharmacol ; 97: 107812, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34091113

RESUMO

BACKGROUND: Behcet's disease (BD) is an autoimmune disorder with the serious possibility of blindness, calling for further research on its pathogenesis. Our aim was to study the metabolite composition of sweat in BD and to identify possible biomarkers. METHODS: Metabolomics analysis was performed on sweat samples from 20 BD patients and 18 normal controls by liquid chromatography tandem mass spectrometry. RESULTS: A significantly different metabolic profile of sweat was observed when BD patients were compared with healthy controls. The result of the orthogonal partial least squared-discrimination analysis (OPLS-DA) showed that these two comparison groups could be separated with a relatively satisfactory fitting degree (R2Y = 0.995 and Q2 = 0.817 in positive ion mode; R2Y = 0.991 and Q2 = 0.721 in negative ion mode). Based on OPLS-DA, a panel of metabolites was selected as candidate biomarkers, including l-citrulline, l-pyroglutamic acid, urocanic acid, 2-oxoadipic acid, cholesterol 3-sulfate, and pentadecanoic acid. CONCLUSION: This is the first report on the metabolite profile of sweat in BD. Our results demonstrated a significantly different metabolite composition of sweat in BD compared to that of healthy controls.


Assuntos
Síndrome de Behçet/diagnóstico , Metaboloma/imunologia , Suor/metabolismo , Síndrome de Behçet/imunologia , Síndrome de Behçet/metabolismo , Biomarcadores/análise , Biomarcadores/metabolismo , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão/métodos , Voluntários Saudáveis , Humanos , Metabolômica/métodos , Suor/imunologia , Espectrometria de Massas em Tandem/métodos
15.
Am J Transl Res ; 12(9): 5924-5939, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042469

RESUMO

Objective: Ovarian cancer is one of the most common gynecological malignancies worldwide, and its mortality rate ranks first among gynecologic cancers. Ceramide synthases are closely related to cancer development. In this study, we investigated the role of ceramide synthase 6 (CerS6) in the development of serous ovarian cancer. Methods: Expression of CerS6 in cancerous and healthy ovarian tissue was assessed by database analysis and immunohistochemistry. The biological role of CerS6 in serous ovarian cancer cells was assessed by CerS6 knockdown followed by cell counting, colony formation, transwell migration, wound healing, and flow cytometry assays and measurement of tumor proliferation in nude mice. Signaling pathway components were analyzed by Western blotting. Gene enrichment was analyzed by GSEA and R, and RNA sequencing was used to compare the transcriptomes of serous ovarian cancer cells with and without CerS6 knockdown. Results: High CerS6 expression in ovarian cancer tissues was closely related to poor prognosis. Knockdown of CerS6 inhibited serous ovarian cancer cell proliferation, invasion, and metastasis and promoted their apoptosis. In addition, CerS6 knockdown increased the proportion of serous ovarian cancer cells in G2/M phase. CerS6 regulates cell cycle through the AKT/mTOR/4EBP1 signaling pathway, which affects cell proliferation and metastasis. The GSEA, R, and RNA sequencing analyses showed that knocking down CerS6 significantly affects cell cycle in serous ovarian cancer cells. Conclusions: CerS6 may have an oncogenic role in ovarian cancer and may represent a new prognostic marker and therapeutic target for serous ovarian cancer.

16.
Int J Clin Exp Pathol ; 13(5): 944-953, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509065

RESUMO

Ovarian cancer (OC) is most common type of gynecologic cancer and is frequently lethal. It is important to determine the pathologic mechanisms underlying OC. ZNF93 is a member of the zinc finger protein family. Abnormal expression of ZNF93 has been observed in various tumor cells. However, its clinical significance and biologic function in ovarian cancer remain unclear. In the present study, we established that ZNF93 expression was highly up-regulated in OC samples and was closely correlated with clinical stage, indicating poor prognosis. We then established that ZNF93 promoted OC cell proliferation and migration. The results of our study may provide insight into the use of ZNF93 as a marker of clinical outcome and as a potential therapeutic target in OC.

17.
Colloids Surf B Biointerfaces ; 194: 111164, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32526636

RESUMO

Due to no specific symptoms and lack of early diagnosis for ovarian cancer, most diagnosed patients are often in the terminal stage resulting that tumor tissue is unable to be resected completely by operation. So postoperative chemotherapy has become an important and indispensable treatment procedure for them. Up to date, it remains a challenge to treat ovarian cancer by an effective chemotherapy strategy. Recently, the strategy of ADDC has been regarded as a highly effective chemotherapy strategy to treat various cancers without any drug carriers. Here a novel ADDC is synthesized by linking a water-soluble antitumor drug floxuridine (Fud) and a water-insoluble antitumor drug chlorambucil (Cb) through the esterification. Then the Fud-Cb conjugate can form stable nanodrugs in water with an average size around 103.0 nm through molecular self-assembly. After internalization of cells, the ester bonds in nanodrugs can be degraded to release free Fud and Cb at a fixed ratio under the intracellular acid conditions, which exhibits the high synergistic effect on ovarian cancer cells. The cytotoxicity test results show that Fud-Cb nanodrugs can efficiently inhibit the growth of ovarian cancer cells. The apoptosis data exhibit that the cell necrotic and apoptotic rate treated with Fud-Cb nanodrugs is about 73.7 % and 18.76 % within 24 h. These results suggest that Fud-Cb nanodrugs based on ADDC strategy can effectively enhance synergistic anticancer efficacy to ovarian cancer.


Assuntos
Antineoplásicos , Clorambucila , Floxuridina , Nanopartículas , Neoplasias Ovarianas , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Clorambucila/administração & dosagem , Clorambucila/farmacologia , Quimioterapia Combinada , Feminino , Floxuridina/administração & dosagem , Humanos , Neoplasias Ovarianas/tratamento farmacológico
18.
Inflammation ; 43(5): 1780-1788, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32435912

RESUMO

Previous studies have pointed out that indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme initiating tryptophan metabolism, plays a role in the regulation of the immune system. This project was designed to investigate the potential role of IDO in monocyte-derived dendritic cells (moDCs) obtained from active Vogt-Koyanagi-Harada (VKH) disease patients. In this study, we found that the IDO mRNA expression and enzyme activity were increased in active VKH patients as compared with healthy controls and patients in remission. To investigate the role of IDO in immune regulation, an effective inhibitor 1-methyl-L-tryptophan (1-MT) was used to suppress its activity in DCs. The results showed that inhibition of IDO with 1-MT significantly decreased the expression of DC marker CD86. IDO inhibition did not affect the cytokine production of IL-6, IL-1ß, TNF-α, IL-10, and TGF-ß in DCs. Downregulation of IDO in DCs also led to the reduction of regulatory T (Treg) cells and an increased CD4+ T cell proliferation. Treatment with 1-MT did not affect the phosphorylation of the MAPK pathway in DCs. In general, our study suggests that IDO may play an important role in the pathogenesis of VKH disease by regulating DC and CD4+ T cell function. Tryptophan deficiency and kynurenine accumulation may account for the complicated effects of IDO. Further research is needed to study the precise tryptophan metabolites that may limit immune responses in VKH disease.


Assuntos
Regulação Enzimológica da Expressão Gênica , Indolamina-Pirrol 2,3,-Dioxigenase/biossíntese , Linfócitos T Reguladores/enzimologia , Síndrome Uveomeningoencefálica/enzimologia , Adulto , Células Cultivadas , Técnicas de Cocultura , Citocinas/metabolismo , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Leucócitos Mononucleares/enzimologia , Leucócitos Mononucleares/patologia , Masculino , Linfócitos T/enzimologia , Linfócitos T/patologia , Linfócitos T Reguladores/patologia , Síndrome Uveomeningoencefálica/genética , Síndrome Uveomeningoencefálica/patologia
19.
Oncol Lett ; 19(4): 3089-3100, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32256809

RESUMO

Primary tumors can secrete many cytokines, inducing tissue damage or microstructural changes in distant organs. The purpose of this study was to investigate changes in texture features in the cerebral tissue of patients with lung cancer without brain metastasis. In this study, 50 patients with lung cancers underwent 3.0-T magnetic resonance imaging (MRI) within 2 weeks of being diagnosed with lung cancer. Texture analysis (TA) was carried out in 8 gray matter areas, including bilateral frontal cortices, parietal cortices, occipital cortices and temporal cortices, as well as 2 areas of bilateral frontoparietal white matter. The same procedure was performed for 57 healthy controls. A total of 32 texture parameters were separately compared between the patients and controls in the different cerebral tissue sites. Texture features among patients based on histological type and clinical stage were also compared. Of the 32 texture parameters, 27 showed significant differences between patients with lung cancer and healthy controls. There were significant differences in cerebral tissue, both gray matter and white matter between patients and controls, especially in several wavelet-based parameters. However, there were no significant differences between tissue at homologous sites in bilateral hemispheres, either in patients or controls. TA detected overt changes in the texture features of cerebral tissue in patients with lung cancer without brain metastasis compared with those of healthy controls. TA may be considered as a novel and adjunctive approach to conventional brain MRI to reveal cerebral tissue changes invisible on MRI alone in patients with lung cancer.

20.
Eur Radiol ; 30(8): 4545-4556, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32166487

RESUMO

OBJECTIVES: To investigate whether subtle changes in radiomics features are present in lung CT images prior to the development of CT-detectable lung metastases in patients with breast cancer. METHODS: Thirty-three radiomics features were measured in the metastasis region (MR) and in matched contralateral tissues (non-metastasis region, NMR) of 29 breast cancer patients at the last CT scan, as well as in the corresponding regions of the patients' pre-metastasis scan (pre-MR and pre-NMR). We also compared them with normal lung tissues (control group, CG) from 29 healthy volunteers. Then, 8 patients from the 29 patients with lung metastases and 8 patients who did not develop lung metastases were chosen for further study of the correlation between radiomics parameters and tumor growth. RESULTS: In the MR vs. NMR and MR vs. CG groups, almost all radiomics features were significantly different. Twenty-six parameters showed significant differences between the pre-MRs and pre-NMRs. Linear fitting demonstrated a significant correlation between 5 features and tumor growth in the metastasis group, but not in the non-metastasis group. Among them, run percentage was the most representative feature. The calculated area under curves (AUCs), based on run percentage for the classification of metastasis and pre-metastasis, were 0.954 and 0.852, respectively. CONCLUSIONS: Radiomics features may allow early detection of lung metastases before they become visually detectable, and the feature run percentage may be a promising image surrogate marker for the microinvasion of tumor cells into the lung tissue. KEY POINTS: • The significant differences in radiomics features between pre-MR and pre-NMR are critical for the early detection of lung metastases. • Five radiomics features show a correlation with tumor growth. • The radiomics feature run percentage may be a potential imaging biomarker for the early detection of lung metastases.


Assuntos
Neoplasias da Mama/patologia , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Tomografia Computadorizada por Raios X/métodos , Área Sob a Curva , Estudos de Coortes , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos
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