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1.
J Immunol Res ; 2020: 1924379, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32411789

RESUMO

Chimeric antigen receptor- (CAR-) T cell therapy is one of the most recent innovative immunotherapies and is rapidly evolving. Like other technologies, CAR-T cell therapy has undergone a long development process, and persistent explorations of the actions of the intracellular signaling domain and make several improvements have led to the superior efficacy when anti-CD19 CAR-T cell treatments in B cell cancers. At present, CAR-T cell therapy is developing rapidly, and many clinical trials have been established on a global scale, which has great commercial potential. This review mainly describes the toxicity of CAR-T cell therapy and the challenges of CAR-T cells in the treatment of solid tumors, and looks forward to future development and opportunities for immunotherapy and reviews major breakthroughs in CAR-T cell therapy.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32329164

RESUMO

C2 -C3 alkyne/alkene separation is of great importance; however, designing materials for an efficient molecular sieving of alkenes from alkynes remains challenging. Now, two hydrolytically stable layered MOFs, [Cu(dps)2 (GeF6 )] (GeFSIX-dps-Cu, dps=4,4'-dipyridylsulfide) and [Zn(dps)2 (GeF6 )] (GeFSIX-dps-Zn), can achieve almost complete exclusion of both C3 H6 and C2 H4 from their alkyne analogues. GeFSIX-dps-Cu displays a notable advanced threshold pressure for alkynes adsorption and thus substantial uptakes at lower pressures, providing record C3 H4 /C3 H6 uptake ratios and capacity-enhanced C2 H2 /C2 H4 sieving for a wide composition range. Metal substitution (Zn to Cu) affords fine tuning of linker rotation and layer stacking, creating slightly expanded pore aperture and interlayer space coupled with multiple hydrogen-bonding sites, allowing easier entrance of alkyne while excluding alkene. Breakthrough experiments confirmed tunable sieving by these MOFs for C3 H4 /C3 H6 and C2 H2 /C2 H4 mixtures.

3.
Arterioscler Thromb Vasc Biol ; 40(5): 1296-1310, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32237906

RESUMO

OBJECTIVE: Integrin ß3 is implicated in numerous biological processes such as its relevance to blood triglyceride, yet whether ß3 deficiency affects this metabolic process remains unknown. Approach and Results: We showed that the Chinese patients with ß3-deficient Glanzmann thrombasthenia had a 2-fold higher serum triglyceride level together with a lower serum LPL (lipoprotein lipase) level than those with an αIIb deficiency or healthy subjects. The ß3 knockout mice recapitulated these phenotypic features. The elevated plasma triglyceride level was due to impaired LPL-mediated triglyceride clearance caused by a disrupted LPL secretion. Further analysis revealed that ß3 directly bound LPL via a juxtamembrane TIH (threonine isoleucine histidine)720-722 motif in its cytoplasmic domain and functioned as an adaptor protein by interacting with LPL and PKD (protein kinase D) to form the PKD/ß3/LPL complex that is required for ß3-mediated LPL secretion. Furthermore, the impaired triglyceride clearance in ß3 knockout mice could be corrected by adeno-associated virus serotype 9 (AAV9)-mediated delivery of wild-type but not TIH720-722-mutated ß3 genes. CONCLUSIONS: This study reveals a hypertriglyceridemia in both ß3-deficient Chinese patients and mice and provides novel insights into the molecular mechanisms of the significant roles of ß3 in LPL secretion and triglyceride metabolism, drawing attention to the metabolic consequences in patients with ß3-deficient Glanzmann thrombasthenia.

4.
Food Funct ; 11(2): 1684-1691, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32037431

RESUMO

Previous studies have shown that curcumin, a bioactive dietary compound with a thiol-reactive α,ß-unsaturated carbonyl moiety, can covalently modify protein thiols. However, most of the previous studies were performed in cultured cells or cell-free enzyme systems, and so it remains unknown whether curcumin could covalently modify proteins after oral administration in vivo. Using click chemistry-based fluorescence imaging, here we show that oral administration of dialkyne-curcumin (Di-Cur), a "click" probe mimicking curcumin, results in covalent modifications of cellular proteins in colon and liver tissues, but not in other tissues, in mice. This result suggests that oral administration of curcumin leads to the formation of the curcumin-protein complex in a tissue-specific manner, which could contribute to the biological effects and/or pharmacokinetics of curcumin. Further studies to elucidate the identities of curcumin-binding proteins could greatly help us to better understand the molecular mechanisms of curcumin, and develop novel strategies for disease prevention.

5.
Clin Neurol Neurosurg ; 191: 105691, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31986364

RESUMO

OBJECTIVES: Current guidelines paid little attention to a unique severe disease about intracranial hematoma owing to aneurysm rupture. We attempted to explore the predictive factors for prognosis in these poor patient population. PATIENTS AND METHODS: One hundred twenty-one aneurysmal subarachnoid hemorrhage combined with intracerebral hematoma patients discharged between 2013 and 2016 were reviewed in this retrospective study. Unfavorable outcome was defined as a modified Rankin Scale (mRS) score of 3, 4, 5, or 6 at 6 months. Multivariable logistic regression was performed to evaluate the association of unfavorable outcome with preoperative and postoperative clinical characteristics. RESULTS: Of 121 patients with intact follow-up data, 34 (28.10 %) had an unfavorable prognosis. The preoperative prognostic model included patients' age, respiratory rate, Hunt-Hess scale, red cell distribution width, and serum sodium at admission. The postoperative prognostic model included patients' age, respiratory rate, red cell distribution width, serum sodium, postoperative delayed cerebral ischemia, and pulmonary infection. Both preoperative and postoperative prognostic models had excellent discrimination with Area Under The Curve (AUC) of 0.864 (P < .001) and 0.898 (P < .001), respectively. CONCLUSION: In clinical practice, we should pay more attention to those old patients with worse admission Hunt-Hess score, presenting deep-slow respiratory and lower serum sodium. Reduction of postoperative delayed cerebral ischemia and pulmonary infection might improve outcomes after aneurysmal SAH with intracerebral hematoma.

6.
mBio ; 11(1)2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911486

RESUMO

Carbon metabolism plays an essential role in bacterial pathogenesis and susceptibility to antibiotics. In Pseudomonas aeruginosa, Crc, Hfq, and a small RNA, CrcZ, are central regulators of carbon metabolism. By screening mutants of genes involved in carbon metabolism, we found that mutation of the tpiA gene reduces the expression of the type III secretion system (T3SS) and bacterial resistance to aminoglycoside antibiotics. TpiA is a triosephosphate isomerase that reversibly converts glyceraldehyde 3-phosphate to dihydroxyacetone phosphate, a key step connecting glucose metabolism with glycerol and phospholipid metabolisms. We found that mutation of the tpiA gene enhances the bacterial carbon metabolism, respiration, and oxidative phosphorylation, which increases the membrane potential and promotes the uptake of aminoglycoside antibiotics. Further studies revealed that the level of CrcZ is increased in the tpiA mutant due to enhanced stability. Mutation of the crcZ gene in the tpiA mutant background restored the expression of the T3SS genes and the bacterial resistance to aminoglycoside antibiotics. Overall, this study reveals an essential role of TpiA in the metabolism, virulence, and antibiotic resistance in P. aeruginosa IMPORTANCE The increase in bacterial resistance against antibiotics imposes a severe threat to public health. It is urgent to identify new drug targets and develop novel antimicrobials. Metabolic homeostasis of bacteria plays an essential role in their virulence and resistance to antibiotics. Recent studies demonstrated that antibiotic efficacies can be improved by modulating the bacterial metabolism. Pseudomonas aeruginosa is an important opportunistic human pathogen that causes various infections. The bacterium is intrinsically resistant to antibiotics. In this study, we provide clear evidence that TpiA (triosephosphate isomerase) plays an essential role in the metabolism of P. aeruginosa and influences bacterial virulence and antibiotic resistance. The significance of this work is in identifying a key enzyme in the metabolic network, which will provide clues as to the development of novel treatment strategies against infections caused by P. aeruginosa.

7.
J Clin Pathol ; 73(1): 7-13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31422373

RESUMO

AIMS: Hereditary protein S (PS) deficiency is one of the natural anticoagulant deficiencies causing thrombophilia. We herein described a young male with recurrent deep venous thrombosis, who was diagnosed as type I PS deficiency with compound heterozygous mutations of PROS1 gene. We aimed to analyse the relationship between the genotype and phenotype detection and investigate the pathological mechanisms of PROS1 mutations causing PS deficiency. METHODS: Genetic analysis of PROS1 gene was carried out by direct sequencing. Thrombin generation potential and the inhibition function of thrombin generation by plasma PS were detected by thrombin generation test (TGT). The mRNA transcription level of mutant PS in vitro was measured by real-time PCR, while the protein level was evaluated by western blot and ELISA. Cellular distribution of the protein was further analysed by immunofluorescence. RESULTS: Compound heterozygous mutations (PROS1 c.1551_1552delinsG, p.Thr518Argfs*39 and PROS1 c.1681C>T, p.Arg561Trp) were identified in the propositus, and the former one was a novel small indel mutation. TGT results showed impaired inhibition of thrombin generation with the addition of activated protein C in his parents with certain heterozygous mutations. In vitro expression study, p.Thr518Argfs*39 mutant produced truncated protein retained in the cytoplasm, while p.Arg561Trp mutant partially affected the secretion of PS. Both mutations are located in C-terminal sex hormone-binding globulin (SHBG)-like domain of PS. CONCLUSIONS: Compound heterozygous mutations identified in the study have strong detrimental effect, causing severe type I PS deficiency in the propositus. SHBG-like domain of PS might play an important role in PS secretion system.


Assuntos
Coagulação Sanguínea/genética , Proteínas Sanguíneas/genética , Heterozigoto , Mutação , Deficiência de Proteína S/genética , Trombose Venosa/genética , Adulto , Proteínas Sanguíneas/metabolismo , Feminino , Predisposição Genética para Doença , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Deficiência de Proteína S/sangue , Deficiência de Proteína S/diagnóstico , Recidiva , Via Secretória , Índice de Gravidade de Doença , Trombina/metabolismo , Trombose Venosa/sangue , Trombose Venosa/diagnóstico
8.
J Clin Lab Anal ; : e23144, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31811687

RESUMO

OBJECTIVE: We aimed to establish the reference range of thromboelastograph (TEG) maximum amplitude (MA) in patients taking antiplatelet drugs. METHODS: Between August 2015 and July 2018, a total of 4614 patients administrating with antiplatelet drugs (clopidogrel and aspirin) were retrospectively analyzed in this study. For MAA parameter, we used the 10th and 90th percentiles to establish a reference range. The Spearman correlation was used for the correlation analysis among the inhibition rate of adenosine diphosphate (ADP%) and MAADP , inhibition rate of arachidonic acid (AA%) and MAAA . Then, through receiver operating characteristic (ROC) curve analysis of the best cutoff point, the reference ranges of MAADP and MAAA could be deduced. Consistency evaluation was performed by statistical analysis of ADP% and MAADP , AA% and MAAA pairing for 4459 patients. RESULTS: The reference range of MAA was 8.1-25.8 mm. The reference range of MAADP was 19.8-43.2 mm, and the corresponding sensitivity of two endpoints was 0.796, 0.856 and specificity were 0.897, 0.904, respectively. The reference range of MAAA was 18.9-37.7 mm, and the corresponding sensitivity of two endpoints was 0.819, 0.829 and specificity were 0.922, 0.896, respectively. The inconsistency rate of ADP% and MAADP , and AA% and MAAA was 20.1% (898 cases) and 16.6% (738 cases), respectively. CONCLUSIONS: The reference range of MAADP and MAAA established by us were better in sensitivity and specificity. MAADP and MAAA were more accurate than conventional inhibition rate analysis in guidance of antiplatelet therapy, especially in patients with excessive low MA or high MAA .

9.
Mol Med Rep ; 20(4): 3463-3474, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485661

RESUMO

Circular RNAs (circRNAs) are a class of non­coding RNAs that are generated via alternative back­splicing, which connects the terminal 5' and 3'ends. Due to their unique loop structure, circRNAs are resistant to ribonucleases and more stable than linear RNAs. In vivo, they are usually highly conserved and stably expressed in tissue/developmental­stage­specific manners. Generally, circRNAs function as microRNA sponges and splicing regulators, as well as in protein binding and transcription. Some circRNAs contain open reading frames with internal ribosomal entry site elements and can thus encode specific proteins. Previously, circRNAs were thought to be erroneous splicing products or by­products of mRNA splicing. With the development of the next­generation sequencing techniques, it has become increasingly clear that circRNAs are abundantly widespread in eukaryotes and that they play significant roles in malignant tumor progression. The present review briefly introduces the biogenesis and functions of circRNAs, as well as summarizes recent research in several common malignancies. The present review also addresses the prospects of circRNAs in clinical applications.


Assuntos
MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , RNA Neoplásico/metabolismo , Animais , Humanos , MicroRNAs/genética , Proteínas de Neoplasias/genética , Neoplasias/genética , Neoplasias/patologia , Fases de Leitura Aberta , RNA Neoplásico/genética
10.
J Infect Dis ; 220(10): 1667-1678, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31419286

RESUMO

BACKGROUND: Trans-translation is a ribosome rescue system that plays an important role in bacterial tolerance to environmental stresses. It is absent in animals, making it a potential treatment target. However, its role in antibiotic tolerance in Pseudomonas aeruginosa remains unknown. METHODS: The role and activity of trans-translation during antibiotic treatment were examined with a trans-translation-deficient strain and a genetically modified trans-translation component gene, respectively. In vitro assays and murine infection models were used to examine the effects of suppression of trans-translation. RESULTS: We found that the trans-translation system plays an essential role in P. aeruginosa tolerance to azithromycin and multiple aminoglycoside antibiotics. We further demonstrated that gentamicin could suppress the azithromycin-induced activation of trans-translation. Compared with each antibiotic individually, gentamicin and azithromycin combined increased the killing efficacy against planktonic and biofilm-associated P. aeruginosa cells, including a reference strain PA14 and its isogenic carbapenem-resistance oprD mutant, the mucoid strain FRD1, and multiple clinical isolates. Furthermore, the gentamicin-azithromycin resulted in improved bacterial clearance in murine acute pneumonia, biofilm implant, and cutaneous abscess infection models. CONCLUSIONS: Combination treatment with gentamicin and azithromycin is a promising strategy in combating P. aeruginosa infections.

11.
Oncol Lett ; 18(2): 1597-1606, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31423227

RESUMO

Traditional clinical features are not sufficient to accurately judge the prognosis of endometrioid endometrial adenocarcinoma (EEA). Molecular biological characteristics and traditional clinical features are particularly important in the prognosis of EEA. The aim of the present study was to establish a predictive model that considers genes and clinical features for the prognosis of EEA. The clinical and RNA sequencing expression data of EEA were derived from samples from The Cancer Genome Atlas (TCGA) and Peking University People's Hospital (PKUPH; Beijing, China). Samples from TCGA were used as the training set, and samples from the PKUPH were used as the testing set. Variable selection using Random Forests (VSURF) was used to select the genes and clinical features on the basis of TCGA samples. The RF classification method was used to establish the prediction model. Kaplan-Meier curves were tested with the log-rank test. The results from this study demonstrated that on the basis of TCGA samples, 11 genes and the grade were selected as the input features. In the training set, the out-of-bag (OOB) error of RF model-1, which was established using the '11 genes', was 0.15; the OOB error of RF model-2, which was established using the 'grade', was 0.39; and the OOB error of RF model-3, established using the '11 genes and grade', was 0.15. In the testing set, the classification accuracy of RF model-1, model-2 and model-3 was 71.43, 66.67 and 80.95%, respectively. In conclusion, to the best of our knowledge, the VSURF was used to select features relevant to EEA prognosis, and an EEA predictive model combining genes and traditional features was established for the first time in the present study. The prediction accuracy of the RF model on the basis of the 11 genes and grade was markedly higher than that of the RF models established by either the 11 genes or grade alone.

12.
Chin Med J (Engl) ; 132(13): 1550-1562, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31268882

RESUMO

BACKGROUND: Management of tumors has become more complex owing to tumor heterogeneity. Fewer studies have been performed on intra-tumor heterogeneity of endometrial cancer (EC) until now. Therefore, it is of great clinical value to explore the intra-tumor heterogeneity of EC based on clinical features and gene expression profiles. METHODS: A total of 1688 patients with EC were screened and 114 patients were finally selected, including specimens from 84 patients with primary EC without relapse (PE) and the paired metastases (P-M) specimens, as well as specimens from 30 patients with primary EC with relapse (RPE) and the paired relapsed EC (P-RE) specimens. Microarray and RNA-seq were used to detect gene expression of EC samples. Clinicopathological characteristics and molecular data were compared between PE and P-M groups and between RPE and P-RE groups to explore the intra-tumor heterogeneity of EC. RESULTS: The clinical intra-tumor spatial heterogeneity of pathological type, grade, ER status, and PR status between PE and P-M were 17.9%, 13.1%, 28.6%, and 28.6%, respectively. The clinical intra-tumor spatiotemporal heterogeneity of pathological type, grade, ER status, and PR status between RPE and P-RE were 16.7%, 33.3%, 25.0%, and 37.5%, respectively. Cluster analysis sorts EC samples based on progression type of lesion and their pathological type. There were differentially expressed genes between PE and P-M and between RPE and P-RE, of which gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were mainly enriched in cell proliferation, the p53 signaling pathway, etc. CONCLUSIONS:: Clinical and molecular data showed that there was spatiotemporal heterogeneity in intra-tumor of EC, which may add to the complexity of diagnosis and therapeutics for EC. Considering the intra-tumor heterogeneity, sequential chemotherapy and precision medicine may be a more suitable treatment plan for EC.


Assuntos
Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Adulto , Idoso , Proliferação de Células/genética , Proliferação de Células/fisiologia , Análise por Conglomerados , Feminino , Humanos , Análise em Microsséries , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Proteína Supressora de Tumor p53/metabolismo , Adulto Jovem
13.
J Cell Mol Med ; 23(8): 4854-4865, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31210425

RESUMO

In the tumour microenvironment (TME), immunogenic cell death (ICD) plays a major role in stimulating the dysfunctional antitumour immune system. Chronic exposure of damage-associated molecular patterns (DAMPs) attracts receptors and ligands on dendritic cells (DCs) and activates immature DCs to transition to a mature phenotype, which promotes the processing of phagocytic cargo in DCs and accelerates the engulfment of antigenic components by DCs. Consequently, via antigen presentation, DCs stimulate specific T cell responses that kill more cancer cells. The induction of ICD eventually results in long-lasting protective antitumour immunity. Through the exploration of ICD inducers, recent studies have shown that there are many novel modalities with the ability to induce immunogenic cancer cell death. In this review, we mainly discussed and summarized the emerging methods for inducing immunogenic cancer cell death. Concepts and molecular mechanisms relevant to antitumour effects of ICD are also briefly discussed.

14.
Neural Plast ; 2019: 2747460, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30996726

RESUMO

Although evidence from studies on blind adults indicates that visual deprivation early in life leads to structural and functional disruption and reorganization of the brain, whether young blind people show similar patterns remains unknown. Therefore, this study is aimed at exploring the structural and functional alterations of the brain of early-blind adolescents (EBAs) compared to normal-sighted controls (NSCs) and investigating the effects of residual light perception on brain microstructure and function in EBAs. We obtained magnetic resonance imaging (MRI) data from 23 EBAs (8 with residual light perception (LPs), 15 without light perception (NLPs)) and 21 NSCs (age range 11-19 years old). Whole-brain voxel-based analyses of diffusion tensor imaging metrics and region-of-interest analyses of resting-state functional connectivity (RSFC) were performed to compare patterns of brain microstructure and the corresponding RSFC between the groups. The results showed that structural disruptions of LPs and NLPs were mainly located in the occipital visual pathway. Compared with NLPs, LPs showed increased fractional anisotropy (FA) in the superior frontal gyrus and reduced diffusivity in the caudate nucleus. Moreover, the correlations between FA of the occipital cortices or mean diffusivity of the lingual gyrus and age were consistent with the development trajectory of the brain in NSCs, but inconsistent or even opposite in EBAs. Additionally, we found functional, but not structural, reorganization in NLPs compared with NSCs, suggesting that functional neuroplasticity occurs earlier than structural neuroplasticity in EBAs. Altogether, these findings provided new insights into the mechanisms underlying the neural reorganization of the brain in adolescents with early visual deprivation.


Assuntos
Cegueira/patologia , Cegueira/fisiopatologia , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Plasticidade Neuronal , Adolescente , Mapeamento Encefálico , Criança , Imagem de Tensor de Difusão , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Substância Branca/patologia , Adulto Jovem
15.
Chin Med J (Engl) ; 132(11): 1314-1321, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-30888986

RESUMO

BACKGROUND: Fusion genes may play an important role in tumorigenesis, prognosis, and drug resistance; however, studies on fusion genes in endometrial cancer (EC) are rare. This study aimed to identify new fusion genes and to explore their clinical significance in EC. METHODS: A total of 28 patients diagnosed with EC were enrolled in this study. RNA sequencing was used to obtain entire genomes and transcriptomes. STAR-comparison and STAR-fusion prediction were applied to predict the fusion genes. Chi-square tests and Student t tests were used to verify the clinical significance with SPSS 13.0 software. RESULTS: New fusion genes were found, and the number of fusion genes varied from 3 to 110 among all patients with EC. The type of fusion genes varied and included messenger RNA (mRNA)-mRNA, long non-coding RNA (lncRNA)-lncRNA, and lncRNA-mRNA. There were six fusion genes with high fusion rates, namely, RP11-123O10.4-GRIP1, RP11-444D3.1-SOX5, RP11-680G10.1-GSE1, NRIP1-AF127936.7, RP11-96H19.1-RP11-446N19.1, and DPH7-PTP4A3. Further studies showed that these fusion genes are related to stage, grade, and recurrence, in which NRIP1-AF127936.7 and DPH7-PTP4A3 were found only in stage III patients with EC. DPH7-PTP4A3 was found in grades 2 and 3, and recurrent patients with EC. CONCLUSION: Fusion genes play an essential role in EC. Six genes that are overexpressed with high fusion rates are identified. NRIP1-AF127936.7 and DPH7-PTP4A3 might be related to stage, and DPH7-PTP4A3 be related to grade and recurrence.


Assuntos
Neoplasias do Endométrio/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Distribuição de Qui-Quadrado , Neoplasias do Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Proteínas de Neoplasias/genética , Proteína 1 de Interação com Receptor Nuclear/genética , Gravidez , Proteínas Tirosina Fosfatases/genética , Análise de Sequência de RNA , Software
16.
Ecotoxicol Environ Saf ; 171: 771-780, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30660970

RESUMO

Examination of plants with strong Cu tolerance and an understanding of their Cu-tolerance mechanisms are of considerable significance for the remediation of Cu-contaminated soil. Although spinach may be a plant with strong Cu tolerance, the threshold of Cu tolerance in this plant and its physiological response mechanisms to Cu are still unclear. In this study, we examined that the effects of different Cu concentrations on the growth parameters, antioxidant enzyme activities, and photosynthesis of spinach seedlings. The results showed that when treated with a low Cu concentration (100 mg L-1 CuSO4), the biomass of spinach seedlings increased, whereas the MDA content, the activities of antioxidant enzymes, Pn, gs and Tr were not significantly different from those in the control (P > 0.05), and Y(II), qP reached their maximum values, indicating that a low Cu concentration (100 mg L-1 CuSO4) had minimal negative effects on the life activities of spinach seedlings. In contrast, when treated with high Cu concentrations (800-1000 mg L-1 CuSO4), the total biomass of spinach seedlings was markedly decreased, the MDA contents increased, antioxidant enzyme activities initially increased and then decreased to varying degrees, the contents of chlorophyll, Pn, Tr, Fv/Fm, qP, NPQ, and Y(II) were all decreased. However the growth of spinach did not terminate, implying that the lethal threshold concentration of Cu for spinach is greater than 1000 mg L-1 CuSO4 used in this study. In summary, spinach exhibits a high tolerance to Cu and can be considered as an alternative plant for the remediation of Cu-contaminated soils.


Assuntos
Cobre/toxicidade , Poluentes do Solo/toxicidade , Spinacia oleracea/efeitos dos fármacos , Clorofila/metabolismo , Fotossíntese/efeitos dos fármacos , Plântula/efeitos dos fármacos , Plântula/fisiologia , Spinacia oleracea/fisiologia , Superóxido Dismutase/metabolismo
17.
Int Urol Nephrol ; 51(3): 559, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30666493

RESUMO

In the original publication, incorrect grant number was included in the Acknowledgements text as 'This study (article) was supported by Natural Science Foundation Y16H050011 of Zhejiang Province, China'. The correct acknowledgement section is given here.

18.
Cell Cycle ; 18(3): 320-332, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30636489

RESUMO

Recent reports indicate that mesenchymal stem cells (MSCs) can fuse with cancer cells to promote cancer progression. Omental adipose-derived stromal cells (O-ASCs) are similar to MSCs, which could be recruited to the stroma in endometrial cancer. The aim of our study was to investigate whether O-ASCs can fuse with endometrial cancer cells to influence cancer cells biological characteristics. We isolated O-ASCs from patients with endometrial cancer. O-ASCs and endometrial cancer cells were labeled with different fluorescent tags and directly co-cultured in an Opera high-throughput spinning-disk confocal microscopy system to observe the processes involved in the fusion, division and migration of hybrid cells. Immunofluorescence and high-throughput imaging analyzes were performed to evaluate proteins related to epithelial-mesenchymal transition (EMT).We found O-ASCs could spontaneously fuse with endometrial cancer cells, including cytomembrane and nuclear fusion. After fusion, endometrial cancer cells assume an elongated and fibroblast-like appearance that exhibit mesenchymal phenotypes. The hybrid cells proliferated through bipolar and multipolar divisions and exhibited more rapid migratory speeds than were observed in the parental cells (P < 0.01), potentially because of their EMT-associated changes, including the down-regulation of E-cadherin and up-regulation of Vimentin. Our results collectively suggest that tumorigenic hybrids spontaneously formed between human O-ASCs and endometrial cancer cells, and that the resulting cells enhanced cancer mobility and heterogeneity by accelerated migration and undergoing multipolar divisions. These data provide a new avenue for investigating the roles of O-ASCs in endometrial cancer.

19.
J Gynecol Oncol ; 30(1): e12, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30479096

RESUMO

OBJECTIVES: To investigate the distribution of serum calcium and the relationship between serum calcium and serum metabolic parameters in endometrial carcinoma (EC) patients. METHODS: Retrospective assessment of patients diagnosed with endometrial cancer from Peking University People's Hospital from 2004 to 2009. Clinical characteristics as well as pretreatment serum calcium, albumin, fasting plasma glucose (FPG), serum triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol (TC) value were extracted from patient records. Serum calcium was corrected for albumin. Unpaired t test and analysis of covariance were used to compare serum calcium among categorical variables. Simple correlation analyses and partial correlation analyses were used to assess the associations between serum calcium and continuous variables. RESULTS: Two-hundred twenty patients were included in this study. After adjusting for confounders, postmenopausal patients had higher total serum calcium (p=0.002) and albumin-corrected serum calcium (p=0.012) than premenopausal patients, endometrioid endometrial carcinoma (EEC) patients had higher total serum calcium than non-endometrioid endometrial carcinoma (NEEC) patients (p=0.037). Significant positive correlations were found between total serum calcium and FPG (p=0.017), TG (p=0.043), HDL (p=0.042), LDL (p<0.001), and TC (p<0.001) after adjusting for multiple variables, and the corrected serum calcium showed no significant correlation with metabolic parameters. CONCLUSION: Total serum calcium might be a more sensitive parameter for metabolic syndrome in endometrioid endometrial cancer patients than lipids.


Assuntos
Cálcio/sangue , Carcinoma Endometrioide/sangue , Neoplasias do Endométrio/sangue , Síndrome Metabólica/sangue , Idoso , Biomarcadores/sangue , Glicemia/análise , Carcinoma Endometrioide/complicações , Neoplasias do Endométrio/complicações , Feminino , Humanos , Menopausa/sangue , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
20.
J Obstet Gynaecol Res ; 45(2): 417-427, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30276973

RESUMO

AIM: This study aimed to confirm whether human omental adipose-derived stem cells (O-ASC) from donors with varying body mass index (BMI, calculated in kg/m2 ) exert different effects on proliferation and migration of endometrial cancer (EC) cells. METHODS: Omental adipose-derived stem cells were isolated from the omental adipose tissues of eight patients who were diagnosed with EC aged from 35 to 56 years. According to the patients' BMI, the O-ASC was divided into two groups: obesity group (BMI ≥ 30) and normal group (18.5 < BMI ≤ 24.9). A broad spectrum cytokine antibody array was used to measure 62 paracrine cytokines secreted by all the O-ASC. MTS assays, direct and indirect co-culture assays were used to assess the effects of O-ASC on proliferation and migration of Hec-1A (estrogen receptor-/progesterone receptor-) and Ishikawa (estrogen receptor+/progesterone receptor+) EC cells. RESULTS: Eight samples of O-ASC were successfully isolated including four samples in obesity group and four in normal group. All the O-ASC displayed typical characteristics of mesenchymal stem cells and possessed similar secretory functions as 26 cytokines were identified in condition medium of O-ASC based on cytokine antibody array. The proliferation of Ishikawa cells was gently stimulated by O-ASC from the two groups (P < 0.05) whereas without any effects on Hec-1A cells. Both horizontal and vertical migrations of EC cells were promoted by O-ASC (P < 0.01). However, there were no statistical differences between the two groups. CONCLUSION: Human O-ASC could influence the proliferation and migration of EC cells in vitro but the effects were not modified by donors' BMI.


Assuntos
Índice de Massa Corporal , Citocinas , Neoplasias do Endométrio , Gordura Intra-Abdominal , Células-Tronco Mesenquimais , Omento , Adulto , Linhagem Celular Tumoral , Citocinas/imunologia , Citocinas/metabolismo , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/metabolismo , Feminino , Humanos , Gordura Intra-Abdominal/imunologia , Gordura Intra-Abdominal/metabolismo , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Obesidade/imunologia , Obesidade/metabolismo , Omento/imunologia , Omento/metabolismo
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