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1.
Plants (Basel) ; 13(8)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38674533

RESUMO

Thaumatin-like proteins (TLPs) comprise a complex and evolutionarily conserved protein family that participates in host defense and several developmental processes in plants, fungi, and animals. Importantly, TLPs are plant host defense proteins that belong to pathogenesis-related family 5 (PR-5), and growing evidence has demonstrated that they are involved in resistance to a variety of fungal diseases in many crop plants, particularly legumes. Nonetheless, the roles and underlying mechanisms of the TLP family in legumes remain unclear. The present review summarizes recent advances related to the classification, structure, and host resistance of legume TLPs to biotic and abiotic stresses; analyzes and predicts possible protein-protein interactions; and presents their roles in phytohormone response, root nodule formation, and symbiosis. The characteristics of TLPs provide them with broad prospects for plant breeding and other uses. Searching for legume TLP genetic resources and functional genes, and further research on their precise function mechanisms are necessary.

2.
ACS Appl Mater Interfaces ; 16(12): 15336-15347, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38485463

RESUMO

Ionogels with excellent mechanical performance and conductivity have been considered as ideal candidates for flexible ionotronics. However, current ionogels suffer from the well-known trade-off between mechanical strength and conductivity. Herein, we construct an ionogel with bicontinuous phase structures, a polymer-rich phase, and a solvent-rich phase. The synergy of the polymer-rich phase as an energy dissipation mechanism and the solvent-rich phase as a conductive nanochannel enables the resultant bicontinuous ionogel to show comprehensive properties, a tensile strength of 4.2 MPa, a toughness of 14.4 MJ/m3, a conductivity of 4.3 mS/cm, excellent self-healing capability, and reprocessability. Benefiting from the remarkable mechanical performance and high conductivity, the integrated supercapacitor achieves a high specific capacitance of 118 mF/cm2 (at a current density of 0.2 mA/cm2) and a capacitance retention of up to 90% (1000 charge-discharge cycles). More significantly, the resultant supercapacitor retains outstanding electrochemical performance even after being subjected to various deformations and even under harsh conditions. This study provides a reliable strategy for developing a high-performance ionogel electrolyte and broadens its application in flexible ionotronics.

3.
ACS Appl Mater Interfaces ; 15(46): 53951-53964, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37960858

RESUMO

The interfacial void and delamination between the hydrogel electrolyte and flexible electrode caused by the inconformal contact and weak adhesion lead to serious performance degradation of solid-state-sandwiched supercapacitors (SCs) upon repetitive deformation. Herein, we propose a hydrogel polymer electrolyte (HPE) engineering strategy for enhancing the interfacial adhesion (Γ) to achieve extremely durable SCs via the soft, tough, and self-adhesive HPE. Using a self-cross-linked poly(N-hydroxyethyl acrylamide)/H3PO4 (PHEAA/H3PO4) HPE as the model, the interfacial adhesion between HPE and polyaniline (PANI)-modified carbon cloth (CC) electrode (CC/PANI) reaches up to 556 J/m2, leading to excellent durability of electrochemical performance under long-term repetitive deformations. The as-assembled sandwiched SC retains 94.14 and 93.62% of initial capacitance after 180° bending and twisting for 100,000 cycles, respectively. Furthermore, benefiting from the addition of H3PO4, the flexible sandwiched SC displays excellent tolerance to low temperatures and delivers a capacitance retention of 98.03% after 180° bending for 10,000 cycles at -20 °C. This work highlights the importance of interfacial adhesion engineering for the design of extremely deformation-tolerable SCs.

5.
IEEE Trans Image Process ; 32: 3397-3412, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37314904

RESUMO

Low-rank tensor completion aims to recover the missing entries of multi-way data, which has become popular and vital in many fields such as signal processing and computer vision. It varies with different tensor decomposition frameworks. Compared with matrix SVD, recently emerging transform t-SVD can better characterize the low-rank structure of order-3 data. However, it suffers from rotation sensitivity, and dimensional limitation (i.e., only effective for order-3 tensors). To alleviate these deficiencies, we develop a novel multiplex transformed tensor decomposition (MTTD) framework, which can characterize the global low-rank structure along all modes for any order- N tensor. Based on MTTD, we propose a related multi-dimensional square model for low-rank tensor completion. Besides, a total variation term is also introduced to utilize the local piecewise smoothness of the tensor data. The classic alternating direction method of multipliers is used to solve the convex optimization problems. For performance testing, we choose three linear invertible transforms including FFT, DCT, and a group of unitary transform matrices for our proposed methods. The simulated and real-data experiments demonstrate the superior recovery accuracy and computational efficiency of our method compared with state-of-the-art ones.

6.
Plant Physiol ; 193(1): 304-321, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37195145

RESUMO

As a fundamental metabolic pathway, autophagy plays important roles in plant growth and development, particularly under stress conditions. A set of autophagy-related (ATG) proteins is recruited for the formation of a double-membrane autophagosome. Among them, the essential roles of ATG2, ATG18, and ATG9 have been well established in plant autophagy via genetic analysis; however, the underlying molecular mechanism for ATG2 in plant autophagosome formation remains poorly understood. In this study, we focused on the specific role of ATG2 in the trafficking of ATG18a and ATG9 during autophagy in Arabidopsis (Arabidopsis thaliana). Under normal conditions, YFP-ATG18a proteins are partially localized on late endosomes and translocated to ATG8e-labeled autophagosomes upon autophagic induction. Real-time imaging analysis revealed sequential recruitment of ATG18a on the phagophore membrane, showing that ATG18a specifically decorated the closing edges and finally disassociated from the completed autophagosome. However, in the absence of ATG2, most of the YFP-ATG18a proteins are arrested on autophagosomal membranes. Ultrastructural and 3D tomography analysis showed that unclosed autophagosome structures are accumulated in the atg2 mutant, displaying direct connections with the endoplasmic reticulum membrane and vesicular structures. Dynamic analysis of ATG9 vesicles suggested that ATG2 depletion also affects the association between ATG9 vesicles and the autophagosomal membrane. Furthermore, using interaction and recruitment analysis, we mapped the interaction relationship between ATG2 and ATG18a, implying a possible role of ATG18a in recruiting ATG2 and ATG9 to the membrane. Our findings unveil a specific role of ATG2 in coordinating ATG18a and ATG9 trafficking to mediate autophagosome closure in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Saccharomyces cerevisiae , Autofagossomos/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/análise , Proteínas Relacionadas à Autofagia/metabolismo , Proteínas de Membrana/metabolismo , Autofagia/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Arabidopsis/metabolismo
7.
J Colloid Interface Sci ; 646: 209-218, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37196494

RESUMO

Construction of Z-scheme heterojunction catalysts with high-speed charge transfer channels for efficient photocatalytic hydrogen production from water splitting is still a challenge. In this work, a lattice-defect-induced atom migration strategy is proposed to construct an intimate interface. The oxygen vacancies of cubic CeO2 obtained from a Cu2O template are used to induce lattice oxygen migration and form SO bonds with CdS to form a close contact heterojunction with a hollow cube. The hydrogen production efficiency reaches ∼12.6 mmol·g-1·h-1 and maintains a high value over 25 h. A series of photocatalytic tests combined with density functional theory (DFT) calculations show that the close contact heterostructure not only promotes the separation/transfer of photogenerated electron-hole pairs but also regulates the intrinsic catalytic activity of the surface. A large number of oxygen vacancies and SO bonds at the interface participate in charge transfer, which accelerates the migration of photogenerated carriers. The hollow structure improves the ability to capture visible light. Therefore, the synthesis strategy proposed in this work, as well as the in-depth discussion of the interface chemical structure and charge transfer mechanism, provides new theoretical support for the further development of photolytic hydrogen evolution catalysts.

8.
Pathol Res Pract ; 241: 154237, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36435095

RESUMO

Pulmonary hyalinizing clear cell carcinoma (HCCC) is a new and rare form of lung salivary gland tumor. Only twenty-two cases have been reported in the literature to date. Furthermore, their clinicopathological features have not been fully characterized. In this paper, we describe the clinicopathological characteristics, immunohistochemical features, and molecular genetic changes in two HCCC cases. We also simultaneously reviewed related literature on similar cases reported. Of the two cases, one was of a 58-year-old man with a 4.3 cm lung tumor, which was the largest among all previously reported cases. The tumor showed an infiltrative growth pattern and perineural and vascular invasion microscopically. Moreover, nuclear grooves, high mitotic figures, and comedo necrosis were observed in addition to classic morphological features. More importantly, rare pseudopapillary structures were observed. The second case was of a 60-year-old woman in whom the tumor was mainly composed of multiple cysts filled with mucus. The remaining focal solid areas of the tumor comprised clear and acidophilic cells embedded in the hyalinizing stroma. Immunohistochemical analysis revealed that the tumor cells of both cases were positive for CK5/6, p40, and p63 expression, but negative for napsin A, TTF-1, and SOX10 expression. The HCCC diagnosis in both cases was validated by fluorescence in-situ hybridization (FISH) examination, which showed Ewing sarcoma breakpoint region 1-activating transcription factor 1 (EWSR1-ATF1) gene fusion. Primary pulmonary HCCC is a rare lung tumor originating from the bronchial mucosa, and its histological features may vary, such as rare pseudopapillary structures and abundant cysts. Thus, the diagnosis should be a combined analysis of histopathological characteristics with immunophenotype and molecular examination, including EWSR1-ATF1 gene fusion detection.


Assuntos
Carcinoma , Cistos , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Pulmão/patologia , Carcinoma/patologia , Muco
9.
Autophagy ; 18(6): 1350-1366, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34657568

RESUMO

In selective macroautophagy/autophagy, cargo receptors are recruited to the forming autophagosome by interacting with Atg8 (autophagy-related 8)-family proteins and facilitate the selective sequestration of specific cargoes for autophagic degradation. In addition, Atg8 interacts with a number of adaptors essential for autophagosome biogenesis, including ATG and non-ATG proteins. The majority of these adaptors and receptors are characterized by an Atg8-family interacting motif (AIM) for binding to Atg8. However, the molecular basis for the interaction mode between ATG8 and regulators or cargo receptors in plants remains largely unclear. In this study, we unveiled an atypical interaction mode for Arabidopsis ATG8f with a plant unique adaptor protein, SH3P2 (SH3 domain-containing protein 2), but not with the other two SH3 proteins. By structure analysis of the unbound form of ATG8f, we identified the unique conformational changes in ATG8f upon binding to the AIM sequence of a plant known autophagic receptor, NBR1. To compare the binding affinity of SH3P2-ATG8f with that of ATG8f-NBR1, we performed a gel filtration assay to show that ubiquitin-associated domain of NBR1 outcompetes the SH3 domain of SH3P2 for ATG8f interaction. Biochemical and cellular analysis revealed that distinct interfaces were employed by ATG8f to interact with NBR1 and SH3P2. Further subcellular analysis showed that the AIM-like motif of SH3P2 is essential for its recruitment to the phagophore membrane but is dispensable for its trafficking in endocytosis. Taken together, our study provides an insightful structural basis for the ATG8 binding specificity toward a plant-specific autophagic adaptor and a conserved autophagic receptor.Abbreviations: ATG, autophagy-related; AIM, Atg8-family interacting motif; BAR, Bin-Amphiphysin-Rvs; BFA, brefeldin A; BTH, benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester; CCV, clathrin-coated-vesicle; CLC2, clathrin light chain 2; Conc A, concanamycin A; ER, endoplasmic reticulum; LDS, LIR docking site; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; LIR, LC3-interacting region; PE, phosphatidylethanolamine; SH3P2, SH3 domain containing protein 2; SH3, Src-Homology-3; UBA, ubiquitin-associated; UIM, ubiquitin-interacting motif.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Autofagossomos/metabolismo , Autofagia , Família da Proteína 8 Relacionada à Autofagia/metabolismo , Proteínas de Transporte/metabolismo
10.
Mater Horiz ; 8(8): 2303-2309, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34846434

RESUMO

Moisture-enabled electricity generation as an emerging new energy-harvesting technology is one of the most fascinating and promising candidates for supplying renewable and clean power. However, existing moist-electric generators (MEGs) can only produce intermittent, brief bursts of power with voltage output less than 1 V, severely restricting their practical applications. Therefore, there is an urgent requirement for next-generation MEG devices with high efficiency and continuous energy harvesting properties. In this work, an ion-gradient-enhanced MEG consisting of electrospun nanofiber fabric and porous active electrode was demonstrated to provide a perfect solution for solving instantaneous and low electric output at the same time. The assembled MEG can produce a sustained voltage output of 1.1 V for 40 000 s without any weak signs, reaching the highest level among all reported MEGs. This remarkable performance mainly arises from the higher concentration difference induced by the introduced active electrode which enhances ion diffusion through the porous nanofiber fabric. In addition, the co-existing streaming potential also contributes to the excellent performance. Beyond power generation, the electrospun nanofiber based MEGs also demonstrate successful applications in self-powered sensors, including ammonia leak monitoring and moisture-temperature sensor for forest-fire detection. This study provides insights for the designing of innovative MEGs and opens a pioneering avenue for future energy conversion.

11.
ACS Appl Mater Interfaces ; 13(47): 56226-56232, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34783544

RESUMO

Water-induced electricity generation as an emerging novel sustainable energy harvesting technology has become a hot research topic recently. Here, we develop a ceramic (SiO2) nanofiber-based water-induced electric generator via the sol-gel electrospinning technique, followed by calcination, which exhibits superior water-induced electricity generation property with significant softness. This superior performance of the SiO2 nanofiber-based generator may be attributed to two aspects: the electrokinetic effect generated by water evaporation force and the ion gradient formed between the top and bottom electrodes. The SiO2 nanofiber-based generator is capable of supplying a continuous voltage and current output of 0.48 V and 0.37 µA, respectively, without weakening after 500 times of bending. Moreover, the high voltage and current output generated by the water-induced generator can be realized in series or parallel and has practical applications, such as in a commercial digital calculator. This environmentally friendly generator, with its low cost, provides great potential for future green energy utilization and opens up new possibilities for portable electronics.

12.
Front Psychiatry ; 12: 537411, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220558

RESUMO

Background: Sustained withdrawal behavior is an obstacle for child development. The present study aimed to preliminarily evaluate the prevalence of social withdrawal tendency in young Chinese children using the Alarm Distress Baby Scale (ADBB) and describe the characteristics of socially withdrawn children. Method: This was a cross-sectional analysis as part of a prospective cohort study. A total of 114 children aged 3-24 months were included. The following instruments were administered: the Chinese version of ADBB, the Ages and Stages Questionnaire (ASQ-3), the Ages and Stages Questionnaire: Social-Emotional (ASQ:SE), and the Infant Temperamental Questionnaire. The tendency of social withdrawal in children was assessed using the ADBB. Social withdrawal was defined as an ADBB score of 5 or above. Student's t-test, χ2 test, and Fisher's exact test were performed to identify the differences in maternal and child characteristics between the children with and without social withdrawal. Age-specific indicators of development in these two groups were also presented. Results: About 16.7% of the children were socially withdrawn. Compared with those without social withdrawal, children with social withdrawal were older and had higher proportions of boys (68.4 vs. 42.1%) and social-emotional development delay (63.2 vs. 0%). In age-specific analyses, social-emotional development was poorer in children with social withdrawal across all age groups from 3 to 24 months. Conclusion: Assessed by the ADBB, the prevalence of social withdrawal tendency in young Chinese children was similar to that reported in the European population; children with social withdrawal tended to have poorer social-emotional development. Further research with larger sample sizes is needed to validate the scale and confirm these findings.

13.
Plants (Basel) ; 10(2)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33672856

RESUMO

Phosphoenolpyruvate carboxylase (PEPC) is a ubiquitous cytosolic enzyme that catalyzes the irreversible ß-carboxylation of phosphoenolpyruvate (PEP) in presence of HCO3- to produce oxaloacetate (OAA) during carbon fixation and photosynthesis. It is well accepted that PEPC genes are expressed in plants upon stress. PEPC also supports the biosynthesis of biocompatible osmolytes in many plant species under osmotic stress. There are five isoforms of PEPC found in peanut (Arachis hypogaea L.), namely, AhPEPC1, AhPEPC2, AhPEPC3, AhPEPC4, and AhPEPC5. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed that the gene expression patterns of these AhPEPC genes were different in mature seeds, stems, roots, flowers, and leaves. The expression of all the plant type PEPC (PTPCs) (AhPEPC1, AhPEPC2, AhPEPC3, and AhPEPC4) was relatively high in roots, while the bacterial type PEPC (BTPC) (AhPEPC5) showed a remarkable expression level in flowers. Principal component analysis (PCA) result showed that AhPEPC3 and AhPEPC4 are correlated with each other, indicating comparatively associations with roots, and AhPEPC5 have a very close relationship with flowers. In order to investigate the function of these AhPEPCs, the fragments of these five AhPEPC cDNA were cloned and expressed in Escherichia coli (E. coli). The recombinant proteins contained a conserved domain with a histidine site, which is important for enzyme catalysis. Results showed that protein fragments of AhPEPC1, AhPEPC2, and AhPEPC5 had remarkable expression levels in E. coli. These three recombinant strains were more sensitive at pH 9.0, and recombinant strains carrying AhPEPC2 and AhPEPC5 fragments exhibited more growth than the control strain with the presence of PEG6000. Our findings showed that the expression of the AhPEPC fragments may enhance the resistance of transformed E. coli to osmotic stress.

14.
Cell Death Dis ; 12(2): 145, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33542185

RESUMO

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play critical roles in human diseases. We aimed to clarify the role of lncRNA X-inactive specific transcript (XIST)/miR-149-3p/forkhead box P3 (FOXP3) axis in ovarian cancer (OC) cell growth. XIST, miR-149-3p and FOXP3 expression in OC tissues and cell lines was assessed, and the predictive role of XIST in prognosis of OC patients was analyzed. The OC cell lines were screened and accordingly treated with silenced/overexpressed XIST plasmid or miR-149-3p mimic/inhibitor, and then the proliferation, invasion, migration, colony formation ability, apoptosis, and cell cycle distribution of OC cells were measured. Effect of altered XIST and miR-149-3p on tumor growth in vivo was observed. Online website prediction and dual luciferase reporter gene were implemented to detect the targeting relationship of lncRNA XIST, miR-149-3p, and FOXP3. XIST and FOXP3 were upregulated, whereas miR-149-3p was downregulated in OC tissues and cells. High XIST expression indicated a poor prognosis of OC. Inhibition of XIST or elevation of miR-149-3p repressed proliferation, invasion, migration, and colony formation ability, and promoted apoptosis and cell cycle arrest of HO-8910 cells. In SKOV3 cells upon treatment of overexpressed XIST or reduction of miR-149-3p, there exhibited an opposite tendency. Based on online website prediction, dual luciferase reporter gene, and RNA pull-down assays, we found that there was a negative relationship between XIST and miR-149-3p, and miR-149-3p downregulated FOXP3 expression. This study highlights that knockdown of XIST elevates miR-149-3p expression to suppress malignant behaviors of OC cells, thereby inhibiting OC development.


Assuntos
MicroRNAs/metabolismo , Neoplasias Ovarianas/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Humanos , Camundongos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Prognóstico , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , Regulação para Cima
15.
Int J Mol Sci ; 22(3)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33513816

RESUMO

Mitochondrial homeostasis refers to the balance of mitochondrial number and quality in a cell. It is maintained by mitochondrial biogenesis, mitochondrial fusion/fission, and the clearance of unwanted/damaged mitochondria. Mitophagy represents a selective form of autophagy by sequestration of the potentially harmful mitochondrial materials into a double-membrane autophagosome, thus preventing the release of death inducers, which can trigger programmed cell death (PCD). Recent advances have also unveiled a close interconnection between mitophagy and mitochondrial dynamics, as well as PCD in both mammalian and plant cells. In this review, we will summarize and discuss recent findings on the interplay between mitophagy and mitochondrial dynamics, with a focus on the molecular evidence for mitophagy crosstalk with mitochondrial dynamics and PCD.


Assuntos
Apoptose/genética , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Mitofagia , Animais , Autofagossomos/genética , Autofagossomos/metabolismo , Homeostase , Mamíferos , Mitocôndrias/genética , Mitofagia/genética , Mitofagia/fisiologia , Chaperonas Moleculares/química , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Plantas , Proteínas Proto-Oncogênicas c-bcl-2/química , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Ubiquitina/genética , Ubiquitina/metabolismo , Proteína X Associada a bcl-2/química , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
16.
Eur J Radiol ; 134: 109467, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33307462

RESUMO

PURPOSE: In populations without contrast enhancement, the imaging features of atypical brain parenchyma inflammations can mimic those of grade II gliomas. The aim of this study was to assess the value of the conventional MR-based radiomics signature in differentiating brain inflammation from grade II glioma. METHODS: Fifty-seven patients (39 patients with grade II glioma and 18 patients with inflammation) were divided into primary (n = 44) and validation cohorts (n = 13). Radiomics features were extracted from T1-weighted images (T1WI) and T2-weighted images (T2WI). Two-sample t-test and least absolute shrinkage and selection operator (LASSO) regression were adopted to select features and build radiomics signature models for discriminating inflammation from glioma. The predictive performance of the models was evaluated via area under the receiver operating characteristic curve (AUC) and compared with the radiologists' assessments. RESULTS: Based on the primary cohort, we developed T1WI, T2WI and combination (T1WI + T2WI) models for differentiating inflammation from glioma with 4, 8, and 5 radiomics features, respectively. Among these models, T2WI and combination models achieved better diagnostic efficacy, with AUC of 0.980, 0.988 in primary cohort and that of 0.950, 0.925 in validation cohort, respectively. The AUCs of radiologist 1's and 2's assessments were 0.661 and 0.722, respectively. CONCLUSION: The signature based on radiomics features helps to differentiate inflammation from grade II glioma and improved performance compared with experienced radiologists, which could potentially be useful in clinical practice.


Assuntos
Encefalite , Glioma , Glioma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Curva ROC , Estudos Retrospectivos
17.
Front Immunol ; 11: 999, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32587587

RESUMO

Objective: Cancer-associated fibroblasts (CAFs) were associated with tumor progression in the tumor microenvironment (TME). However, their immunosuppressive roles in protecting cancer cells from the attack by cytotoxic T lymphocytes (CTLs) are not fully clear. In this study, we investigated whether and how CAFs regulate tumor-infiltrating lymphocytes as well as their role in tumor immunosuppression. Methods: Eighty-three cases of ovarian cancer and 10 controls were analyzed for CAFs and CD8+ tumor-infiltrating lymphocytes by gene array and immunohistochemistry. We evaluated presenilin 1 (PS1) expression in CAFs, CTL penetration, tumor burden, dendritic cell function, and migration of tumor-infiltrating lymphocytes and their function in vivo and in vitro after silencing PS1. In addition, the pathway via which PS1 affects the TME was also evaluated. Results: PS1 was highly expressed in CAFs, and its silencing significantly promoted CD8+ CTL proliferation and penetration in multiple ovarian models (p < 0.05), resulting in tumor regression and growth inhibition. Interleukin (IL)-1ß was identified as a major immune inhibitor in the TME, and it was significantly decreased after PS1 silencing (p < 0.05), which was regulated by the WNT/ß-catenin pathway. It was also showed that high expression of IL-1ß in CAFs inhibits CTL penetration significantly (p < 0.05). Conclusion: Highly expressed PS1 in CAFs plays a crucial role in regulating tumor-infiltrating lymphocyte populations in the TME via the WNT/ß-catenin pathway. Targeting PS1 may retrieve functional CTLs in the TME and improve the efficacy of current immunotherapies.


Assuntos
Fibroblastos Associados a Câncer/imunologia , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Ovarianas/metabolismo , Presenilina-1/metabolismo , Linfócitos T Citotóxicos/imunologia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Ovarianas/imunologia , Presenilina-1/genética , Microambiente Tumoral , Via de Sinalização Wnt
18.
Biosci Rep ; 40(4)2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32190895

RESUMO

Ovarian cancer (OC) is a malignant tumor with high mortality in women. Although cancer patients initially respond to paclitaxel chemotherapy following surgery, most patients will relapse after 12-24 months and gradually die from chemotherapy resistance. In OC, cancer cells become resistant to paclitaxel chemotherapy under hypoxic environment. The miR-27a has been identified as an oncogenic molecular in ovarian cancer, prostate cancer, liver cancer etc. In addition, the miR-27a is involved in hypoxia-induced chemoresistance in various cancers. However, the role of miR-27a in hypoxia-induced OC resistance remains unclear. The aim of the present study was to investigate the regulatory mechanism of miR-27a in hypoxia-induced OC resistance. The expression of HIF-1α induced Hypoxia overtly up-regulated. At the same time, hypoxia increased viability of Skov3 cells and decreased cell apoptosis when treated with paclitaxel. The expression of the miR-27a was obviously up-regulated under hypoxia and involved in hypoxia-induced paclitaxel resistance. Follow-up experiments portray that miR-27a improved paclitaxel resistance by restraining the expression of APAF1 in OC. Finally, we further elucidated the important regulatory role of the miR-27a-APAF1 axis in OC through in vivo experiments. According to our knowledge, we first reported the regulation of miR-27a in hypoxia-induced chemoresistance in OC, providing a possible target for chemoresistance treatment of OC.


Assuntos
Fator Apoptótico 1 Ativador de Proteases/genética , Carcinoma Epitelial do Ovário/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Hipóxia Celular/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , MicroRNAs/agonistas , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Paclitaxel/uso terapêutico , RNA Interferente Pequeno/metabolismo , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Chemosphere ; 244: 125499, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32050328

RESUMO

Thallium (Tl) is a highly toxic heavy metal that has been suggested to be responsible for oxidative stress and mitochondrial dysfunction. However, few studies have focused on the relationship of prenatal Tl exposure with children's neurobehavioural development. The purpose of our study was to investigate the association between prenatal Tl exposure and attention-deficit/hyperactivity disorder (ADHD) symptoms in 36-month-old children. We used data from 2851 mother-newborn pairs from the Ma'anshan Birth Cohort Study (MABC); serum Tl concentration was assessed in the first, second and third trimesters of pregnancy as well as in the umbilical cord blood. We assessed ADHD symptoms in the children using the Chinese version of the Conners abbreviated symptom questionnaire (C-ASQ). The adjusted odds ratio (OR) for the risk of ADHD symptoms was 2.00 [95% confidence interval (CI): 1.20, 3.32] and 2.08 (95% CI: 1.26, 3.43) for the third (60.25-75.21 ng/L) and fourth quartiles of serum Tl (>75.21 ng/L), respectively, in the second trimester of pregnancy, in comparison with the first quartile of serum Tl (<50.86 ng/L). The risk of ADHD symptoms was elevated among boys exposed to the fourth quartile of serum Tl in the second trimester of pregnancy (adjusted OR 2.08, 95% CI: 1.13, 3.83). Our results demonstrated that high levels of Tl exposure in the second trimester of pregnancy were related to a higher risk of ADHD symptoms in 36-month-old children, and the association of higher serum Tl exposure in the second trimester with ADHD symptoms was only found in boys.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/sangue , Efeitos Tardios da Exposição Pré-Natal/sangue , Tálio/sangue , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Pré-Escolar , Estudos de Coortes , Feminino , Sangue Fetal , Humanos , Recém-Nascido , Masculino , Mães , Gravidez , Segundo Trimestre da Gravidez/sangue , Terceiro Trimestre da Gravidez/sangue , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Fatores Sexuais , Tálio/toxicidade
20.
Front Oncol ; 10: 602553, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33659209

RESUMO

PURPOSE: Diffuse midline gliomas (DMG) with H3K27M mutations have been identified as a rare distinctive entity with unique genetic features, varied molecular alterations, and poor prognosis. The current study aimed to evaluate the clinical characteristics and profile of molecular markers on patients with a DMG harboring H3K27M mutations, and explore the impact of this genetic makeup on overall survival. METHODS: We retrospectively analyzed 43 consecutive patients diagnosed with a DMG harboring H3K27M mutations (age range 3 to 75 years) and treated in a tertiary institution within China between January 2017 to December 2019. Various clinical and molecular factors were evaluated to assess their prognostic value in this unique patient cohort. RESULTS: The median overall survival (OS) was 12.83 months. Preoperative Karnofsky Performance Score (KPS) and adjuvant radiotherapy were found to be independent clinical parameters influencing the OS by multivariate analysis (p = 0.027 and p < 0.001 respectively). Whereas extent of tumor resection failed to demonstrate statistical significance. For molecular markers, P53 overexpression was identified as a negative prognostic factor for overall survival by multivariate analysis (p = 0.030). CONCLUSION: Low preoperative KPS, absence of radiotherapy and P53 overexpression were identified as predictors of a dismal overall survival in patients with DMG and H3K27M mutations.

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