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1.
Nat Ecol Evol ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32203475

RESUMO

The transient larva-bearing biphasic life cycle is the hallmark of many metazoan phyla, but how metazoan larvae originated remains a major enigma in animal evolution. There are two hypotheses for larval origin. The 'larva-first' hypothesis suggests that the first metazoans were similar to extant larvae, with later evolution of the adult-added biphasic life cycle; the 'adult-first' hypothesis suggests that the first metazoans were adult forms, with the biphasic life cycle arising later via larval intercalation. Here, we investigate the evolutionary origin of primary larvae by conducting ontogenetic transcriptome profiling for Mollusca-the largest marine phylum characterized by a trochophore larval stage and highly variable adult forms. We reveal that trochophore larvae exhibit rapid transcriptome evolution with extraordinary incorporation of novel genes (potentially contributing to adult shell evolution), and that cell signalling/communication genes (for example, caveolin and innexin) are probably crucial for larval evolution. Transcriptome age analysis of eight metazoan species reveals the wide presence of young larval transcriptomes in both trochozoans and other major metazoan lineages, therefore arguing against the prevailing larva-first hypothesis. Our findings support an adult-first evolutionary scenario with a single metazoan larval intercalation, and suggest that the first appearance of proto-larva probably occurred after the divergence of direct-developing Ctenophora from a metazoan ancestor.

2.
Sci Total Environ ; 721: 137696, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32182464

RESUMO

Residential coals are still inevitable using in developing areas in China. Clean coal briquettes, normally using alkaline substance such as lime or red mud (RM) as the additive, were helpful in pollution emission reduction even without changes of stoves. Studies of atmospheric polycyclic aromatic hydrocarbons (PAHs) emission characteristics from RM clear coal combustion were limited. In this study, emission factors (EFs), sources profiles, and health risks of polycyclic aromatic hydrocarbons (PAHs) in PM2.5 were investigated for raw coal chunks and clean coal (with red mud) through combustion experiments. EFs of total PAHs were found to be 160.1 ± 100.9 mg·kg-1 and 19.4 ± 6.1 mg·kg-1 for bituminous and anthracite raw coal chunks (B-C and A-C), respectively. EFs values were highest for parent PAHs (p-PAHs), followed by oxygenated PAHs (o-PAHs), alkylated PAHs (a-PAHs), and nitro PAHs (n-PAHs). EFs of p-PAHs account for 80% and 52% of total PAHs emissions for B-C and A-C, respectively, while those for o-PAHs are 22.9% and 44.9%, demonstrating residential coal combustion as a significant primary source for p-PAHs and o-PAHs. Clean coals were developed through cold-press technology with red mud (RM) as additive, and clean coals with RM contents of 10% are referred to as B-10% (bituminous) and A-10% (anthracite). Compared to raw coals chunks, EFs were reduced from 128.1, 2.5, 29.3 mg·kg-1 and 161.8 µg·kg-1 to 83.5, 1.3, 16.4 mg·kg-1 and 102.2 µg·kg-1 by B-10%, and from 10.1, 0.6, 8.7 mg·kg-1 and 20.6 µg·kg-1 to 11.9, 0.2, 2.4 mg·kg-1 and 15.3 µg·kg-1 by A-10% for p-PAHs, o-PAHs, a-PAHs and n-PAHs, respectively. Diagnostic ratios of 5-Nitroacenaphthene / Acenaphthene (0.02-0.05 for coal, 0.0002 for biomass) can be used to separate residential coal and biomass burning in source analysis. When B-C was replaced by B-10%, both noncancer (0.58 to 0.33 for male, 1.65 to 0.95 for female in hazard quotient) and cancer risks (5.68 × 10-4 to 2.73 × 10-4 for male, 2.63 × 10-3 to 1.27 × 10-3 for female) can be reduced. o-PAHs should be paid more attention because of its high cancer risks caused by 6H-Benzo(C,D)Pyrene-6-One (1.74 × 10-5 for male, 8.07 × 10-5 for female), which are even more than the total risks caused by n-PAHs (3.59 × 10-7 for male, 1.66 × 10-6 for female). Results from this study highlighted the environment and health effects of PAHs originated from residential coal combustion, and proposed an effective way by using clean coal to alleviate the associated negative impacts.

3.
Curr Eye Res ; : 1-8, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32078434

RESUMO

Purpose/Aim: Corneal stromal fibroblasts are connected to each other via gap junctions, which contribute to maintenance of corneal homeostasis. Viral infection of the corneal stroma can result in inflammation and scarring. The effects of polyinosinic-polycytidylic acid [poly(I:C)], an analog of viral double-stranded RNA, on gap junctional intercellular communication (GJIC) in cultured human corneal fibroblasts (HCFs) were examined.Materials and Methods: Cultured HCFs were exposed to poly(I:C) in the absence or presence of inhibitors of mitogen-activated protein kinase (MAPK) signaling or the antioxidant N-acetyl-L-cysteine (NAC). Expression of the gap junction protein connexin 43 (Cx43) was examined by immunoblot and immunofluorescence analyses. The level of Cx43 mRNA or microRNA-21 or -130a was determined by quantitative reverse transcription-polymerase chain reaction analysis. GJIC was measured with a dye coupling assay. The amount of malondialdehyde and the activity of superoxide dismutase (SOD) were measured with assay kits.Results: Exposure of HCFs to poly(I:C) resulted in down-regulation of Cx43 expression and GJIC activity as well as in up-regulation of microRNA-21 expression. Poly(I:C) increased the amount of malondialdehyde and reduced the activity of SOD in the cells, and these effects were prevented by NAC. The inhibitory effects of poly(I:C) on both Cx43 expression and GJIC activity were attenuated by NAC and by c-Jun NH2-terminal kinase (JNK) inhibitor II.Conclusions: Poly(I:C) inhibited Cx43 expression and GJIC in cultured HCFs, possibly as a result of the associated up-regulation of microRNA-21. Poly(I:C) also increased oxidative stress in these cells, and such stress together with signaling by the MAPK JNK was implicated in the effects of poly(I:C) on Cx43 expression and GJIC activity. Down-regulation of GJIC activity among corneal fibroblasts by double-stranded RNA may thus contribute to the disruption of stromal homeostasis during viral infection of the cornea.

4.
J Food Sci ; 85(3): 682-688, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31999363

RESUMO

The aim of this study was to evaluate the effect of µ-calpain oxidation on Coregonus peled myofibrillar protein degradation. In the present study, a hydroxyl radical oxidation system was selected to investigate oxidative modification on µ-calpain activity and its degradation on C. peled myofibrillar protein. When subjected to oxidation, the carbonyl content of µ-calpain significantly increased with the increasing of oxidation levels, and oxidation modification promoted the µ-calpain activity. Incubation of C. peled myofibrillar protein with oxidized µ-calpain resulted in the enhanced degradation of myosin heavy chains, actin, and troponin T, but the degradation of desmin at higher levels of oxidation was slightly inhibited, based on sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blotting. This study suggests that oxidation treatment of µ-calpain could accelerate myofibrillar proteolysis through regulating the enzyme activity during postmortem aging. PRACTICAL APPLICATION: Endogenous proteases, especially µ-calpain, are reported to be involved in fish softening during early postmortem storage, which is critical to muscle quality. The cysteine residues of proteins are particularly sensitive to oxidation. The investigation of the effect of oxidation on µ-calpain (a cysteine protease) activity allows for the monitoring of its role in the postmortem proteolysis of fish myofibrils and the associated softening of fish meat, in an attempt to minimize this softening.

5.
Sensors (Basel) ; 20(1)2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31948002

RESUMO

A rich line of works focus on designing elegant loss functions under the deep metric learning (DML) paradigm to learn a discriminative embedding space for remote sensing image retrieval (RSIR). Essentially, such embedding space could efficiently distinguish deep feature descriptors. So far, most existing losses used in RSIR are based on triplets, which have disadvantages of local optimization, slow convergence and insufficient use of similarity structure in a mini-batch. In this paper, we present a novel DML method named as global optimal structured loss to deal with the limitation of triplet loss. To be specific, we use a softmax function rather than a hinge function in our novel loss to realize global optimization. In addition, we present a novel optimal structured loss, which globally learn an efficient deep embedding space with mined informative sample pairs to force the positive pairs within a limitation and push the negative ones far away from a given boundary. We have conducted extensive experiments on four public remote sensing datasets and the results show that the proposed global optimal structured loss with pairs mining scheme achieves the state-of-the-art performance compared with the baselines.

6.
Plant Physiol Biochem ; 146: 259-268, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31778931

RESUMO

The HD-ZIP Ⅳ transcription factors have been identified and functional characterized in many plant species. However, no tobacco HD-ZIP IV gene has been isolated, and it is not yet known whether HD-ZIP IV genes are involved in controlling flavonols accumulation in plants. Here, we cloned a HD ZIP gene named NtHDG2 from Nicotiana tabacum, which belongs to the class IV of HD-ZIP family, and the NtHDG2-GFP fusion protein is localized to the nucleus. We further observed that the flavonols contents in the NtHDG2 overexpression leaves increase to 1.9-4.5 folds of that in WT plants, but in the NtHDG2-RNAi plants the flavonols contents reduce to 20.9%-52.7% of that in WT plants. The transcriptions of one regulatory gene NtMYB12, and three structural genes (NtPAL, NtF3'H, NtF3GT), contributing to flavonols biosynthesis, were significantly induced by NtHDG2. However, the transcription level of NtNAC002, a flavonols biosynthesis repressor, was also significantly up-regulated in NtHDG2-overexpression lines, but significantly down-regulated in the RNAi lines, indicating that HDG2 regulates the synthesis of flavonols as a complex regulatory network. Moreover, ectopic expression of NtHDG2 gene promoted the transcription of several AP2/ERF genes, including NtERF1-5, NtERF109, NtDREB1, and NtCIPK11, which participate in regulating root development and resistance to abiotic stresses. Our findings reveal the new function of HD-ZIP IV transcription factors in flavonoids biosynthesis, and indicate that HD-ZIP IV members may play an important role in plant resistance to abiotic stress. The NtHDG2 gene provides a promising target for genetically manipulating to increase the amounts of flavonols in tobacco leaves.

7.
Pest Manag Sci ; 76(1): 75-84, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31140683

RESUMO

BACKGROUND: Honeydew is valuable food source for predators that can build predator numbers and strengthen biological control. Honeydew excreted by hemipterans often supplements the diets of their predators and parasitoids. However, dense sticky honeydew also creates a difficult foraging environment, potentially limiting predator efficiency. RESULTS: We examined the benefits and costs of honeydew excreted by the pear psylla (Cacopsylla chinensis [Yang and Li]) for its key predator in much of Asia, the anthocorid bug Orius sauteri (Poppius). We found these predators spent more time foraging and laid more eggs in the presence of psyllid honeydew compared to the control. However, predators more often foraged among psylla without honeydew than those coated in honeydew. This suggests that while O. sauteri recognized honeydew as a useful cue to prey presence, the predators were more likely to attack pear psylla lacking the sugary excretion. In foraging trials, honeydew consistently reduced the number of psyllids killed by the predator, suggesting it limited O. sauteri mobility or reduced the nutritional value of psyllids as prey. We also found slowed development, reduced longevity, and reduced fecundity of O. sauteri reared on moth eggs (Sitotroga cerealella [Olivier]) coated in honeydew compared to those reared on moth eggs alone. CONCLUSION: Altogether, our results suggest that psyllid honeydew could serve as a prey-location and oviposition cue for O. sauteri. However, honeydew also limited predator foraging with the potential to limit biological control. More generally, honeydew might form an important type of defense for stationary feeders like psyllids. © 2019 Society of Chemical Industry.


Assuntos
Heterópteros , Pyrus , Animais , Ásia , Feminino , Mariposas , Oviposição
8.
Chem Commun (Camb) ; 55(100): 15137-15140, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31789333

RESUMO

A fluorescent probe (TPA-BTD-MT) was designed to monitor cyanide ions (CN-) with a "turn-on" response, changing from "turn-off" behavior due to the structural change. TPA-BTD-MT exhibited high selectivity for sensing CN- in several food samples and was successfully used for imaging CN- in living cells and animals with strong "turn-on" fluorescence.


Assuntos
Cianetos/análise , Corantes Fluorescentes/química , Análise de Alimentos/métodos , Imagem Óptica , Compostos de Anilina/química , Animais , Linhagem Celular Tumoral , Limite de Detecção , Manihot/química , Manihot/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência , Teoria Quântica , Solanum tuberosum/química , Solanum tuberosum/metabolismo
9.
Environ Int ; 133(Pt B): 105252, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31678907

RESUMO

Solid (biomass and coal) fuels burned for residential heating are major sources of atmospheric volatile organic compounds (VOCs). In this study, VOC samples were collected in-situ from chimneys in 10 typical heating scenarios in rural areas of the Guanzhong Plain. A modified SUMA canister approach was then employed, followed by gas chromatography/mass spectrometry analysis. Emission factors (EFs) (as received basis) of targeted non-methane VOCs (NMVOCs) varied from 90.3 ±â€¯29.3 to 12300 ±â€¯1510 mg kg-1 in descending order of fuel wood > maize straw > bitumite ≫ anthracite (p < 0.05). Both clean stove and coal briquetting technologies effectively reduced VOC EFs compared with traditional heating methods. The EFs of methane (CH4) had similar characteristics to those of NMVOCs. However, they yielded different correlations with CO because of their differing mechanisms of formation. Coefficient of divergence (CD) values showed that a semi-gasifier has a limited effect on changing VOC profiles compared with a traditional stove using the same fuels. However, different types of fuel produce CD values over 0.50, which should therefore be classified as different sub-categories in source apportionment models. Correlation analysis showed that volatile matter content (V%) and modified combustion efficiency (MCE) were the two primary factors influencing NMVOC and CH4 emissions. A stepwise linear regression analysis showed that V%, MCE, and element nitrogen content (N%) can be used to predict total VOC (TVOCs, including CH4 and NMVOCs) emissions with regression coefficients of 0.23, -72.8 and -6.53, respectively (R2 = 0.92, p < 0.001). Ozone formation potential (OFP) EFs from burning solid fuel ranged from 72 to 18680 mg kg-1, with an approximate 50% contribution from alkenes. VOCs from burning solid fuel were equivalent to 62 to 22200 mg kg-1 secondary organic aerosol formation potential (SOAP), most of which (>95%) were contributed by aromatics. A semi-gasifier and coal briquettes were effective in reducing TVOC emissions, even when used in conjunction with a traditional stove and fuels. It is estimated that over 15,000 ton year-1 emissions can be reduced in Guanzhong Plain by adopting a semi-gasifier and coal briquettes, resulting in a 57,000 and 65,000 ton year-1 reduction of OFP and SOAP emissions, respectively. These results demonstrate that the use of clean heating technologies in Guanzhong Plain has considerable potential in relation to emissions reduction and thus provides a feasible solution to mitigate VOCs and related secondary pollutants emitted by residential solid fuel burning.


Assuntos
Poluentes Atmosféricos/química , Calefação/instrumentação , Compostos Orgânicos Voláteis/química , Aerossóis/análise , Biomassa , China , Carvão Mineral , Monitoramento Ambiental , Produtos Domésticos , Humanos , Ozônio/análise , Madeira/química
10.
Plant Pathol J ; 35(4): 372-380, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31481860

RESUMO

Pseudomonas syringae pv. actinidiae (Psa) is by far the most important pathogen of kiwifruit. Sustainable expansion of the kiwifruit industry requires the use of Psa-tolerant or resistant genotypes for the breeding of tolerant cultivars. However, the resistance of most existing kiwifruit cultivars and wild genotypes is poorly understood, and suitable evaluation methods of Psa resistance in Actinidia have not been established. A unique in vitro method to evaluate Psa resistance has been developed with 18 selected Actinidia genotypes. The assay involved debarking and measuring the lesions of cane pieces inoculated with the bacterium in combination with the observation of symptoms such as callus formation, sprouting of buds, and the extent to which Psa invaded xylem. Relative Psa resistance or tolerance was divided into four categories. The division results were consistent with field observations. This is the first report of an in vitro assay capable of large-scale screening of Psa-resistance in Actinidia germplasm with high accuracy and reproducibility. The assay would considerably facilitate the breeding of Psa-resistant cultivars and provide a valuable reference and inspiration for the resistance evaluation of other plants to different pathogens.

11.
Pathol Res Pract ; 215(10): 152616, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31493939

RESUMO

OBJECTIVES: To explore the expression level and to investigate the clinical associations of the long non-coding RNA (lncRNA) FAM83H-AS1 in gastric cancer. METHODS: The expression level of FAM83H-AS1 were explored by quantitative reverse transcription PCR (qRT-PCR). The Cox regression models as well as log-rank test were utilized to investigate whether FAM83H-AS1 expression could be used as a prognosis predictor. The value of FAM83H-AS1 as a diagnostic biomarker was evaluated by receiver operating curves (ROC). RESULTS: Aberrantly upregulation of FAM83H-AS1 was identified in gastric cancer in comparison with that in normal tissues. We also found that upregulated FAM83H-AS1 was a risk factor relating to OS and DFS. The area under curve (AUC) was 0.8603 and 0.6778 for gastric cancer and lymph node metastasis, respectively. CONCLUSION: Our results indicated that FAM83H-AS1 may function as an oncogene in gastric cancer and could be used as a prognosis predictor or diagnostic biomarker in gastric cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas/metabolismo , Neoplasias Gástricas/metabolismo , Regulação para Cima , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas/genética , Neoplasias Gástricas/patologia
12.
Environ Sci Pollut Res Int ; 26(33): 34357-34367, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31493079

RESUMO

To investigate the acid-extractable heavy metals in fine particulate matter (PM2.5) over Xi'an, China, 24-h PM2.5 samples were collected every 3 days from December 2015 through November 2016. The bioavailable fraction, termed here the bioavailability index (BI), of PM2.5-bound metal (As, Ba, Cd, Co, Cu, Mn, Ni, Pb, Ti, V, and Zn) and potential influencing factors, including relative humidity, temperature, air pressure, wind speed, visibility, PM2.5, and SO2 concentrations, were assessed in this study. The annual average PM2.5 concentration was 50.6 ± 35.6 µg m-3, 1.5 times higher than the Chinese national secondary standard. Zn, Ti, and As were the most abundant elements of those analyzed in the PM2.5 samples, accounting for 72.1% of total quantity. The seasonal variations and enrichment factor analysis of heavy metals revealed that coal combustion in winter was a crucial source of Pb, Co, Cu, and Zn; and dust resuspension in spring contributed considerable Mn, Ti, and V. The acid-extractable fractions of the measured metals varied. Pb, Cu, Mn, and Zn exhibited relatively high acid-extractable concentrations and BI values. Pb was mostly in the acid-extractable fraction in PM2.5, with a mean BI value of 66.7%, the highest in summer (69.8%) and lowest in winter (63.7%). Moreover, the BIs of PM2.5-bound heavy metals were inversely related to temperature and wind speed, whereas positively correlated with relative humidity, SO2, and PM2.5 concentration in this study. This study assessed the seasonal distribution and meteorological influence of acid-extractable heavy metals, providing a deeper understanding of atmospheric heavy metal pollution in Xi'an, China.


Assuntos
Poluentes Atmosféricos/química , Poluição do Ar/estatística & dados numéricos , Monitoramento Ambiental , Metais Pesados/química , Conceitos Meteorológicos , Material Particulado/química , Ácidos/análise , Poluentes Atmosféricos/análise , Disponibilidade Biológica , China , Poeira/análise , Metais Pesados/análise , Meteorologia , Material Particulado/análise , Estações do Ano
13.
Anal Chim Acta ; 1079: 192-199, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31387710

RESUMO

Herein, a zinc ion (Zn2+)-triggered aggregation induced emission enhancement (AIEE) fluorescence "on-off-on" nanoswitch was fabricated for inorganic pyrophosphate (PPi) and inorganic pyrophosphatase (PPase) activity detection. Dual ligand functionalized Au NCs were utilized as the substrate of the AIEE nanoswitch. The introduction of Zn2+ can cause Au NCs aggregated along with the enhanced fluorescence. After the addition of PPi, aggregated Au NCs disaggregated along with decreased fluorescence due to the competitive combination between PPi and Zn2+ (on-off). When PPase was introduced, PPi was hydrolyzed and release Zn2+, resulting in aggregated Au NCs along with enhanced fluorescence again (off-on). On the basis of this, highly selective and sensitive detection PPi (liner range from 0.1 to 300 µM) and PPase activity (liner range from 0.1 to 10 mU) can be achieved. The detection limits are 0.04 µM for PPi and 0.03 mU for PPase, respectively. Furthermore, the as-prepared Zn2+-triggered AIEE nanoswitch was successfully used for quantitative analysis of PPase activity in human serum with satisfactory spiked recoveries, and applied for the inhibitors screening.


Assuntos
Difosfatos/sangue , Pirofosfatase Inorgânica/sangue , Nanopartículas Metálicas/química , Zinco/química , Ensaios Enzimáticos/métodos , Fluorescência , Ouro/química , Humanos , Limite de Detecção , Espectrometria de Fluorescência/métodos
14.
mBio ; 10(4)2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431550

RESUMO

The blast fungus initiates infection using a heavily melanized, dome-shaped infection structure known as the appressorium, which forcibly ruptures the cuticle to enter the rice leaf tissue. How this process takes place remains not fully understood. Here, we used untargeted metabolomics analyses to profile the metabolome of developing appressoria and identified significant changes in six key metabolic pathways, including early sphingolipid biosynthesis. Analyses employing small molecule inhibitors, gene disruption, or genetic and chemical complementation demonstrated that ceramide compounds of the sphingolipid biosynthesis pathway are essential for normal appressorial development controlled by mitosis. In addition, ceramide was found to act upstream from the protein kinase C-mediated cell wall integrity pathway during appressorium repolarization and pathogenicity in rice blast. Further discovery of the sphingolipid biosynthesis pathway revealed that glucosylceramide (GlcCer) synthesized by ceramide is the key substance affecting the pathogenicity of Magnaporthe oryzae Our results provide new insights into the chemical moieties involved in the infection-related signaling networks, thereby revealing a potential target for the development of novel control agents against the major disease of rice and other cereals.IMPORTANCE Our untargeted analysis of metabolomics throughout the course of pathogenic development gave us an unprecedented high-resolution view of major shifts in metabolism that occur in the topmost fungal pathogen that infects rice, wheat, barley, and millet. Guided by these metabolic insights, we demonstrated their practical application by using two different small-molecule inhibitors of sphingolipid biosynthesis enzymes to successfully block the pathogenicity of M. oryzae Our study thus defines the sphingolipid biosynthesis pathway as a key step and potential target that can be exploited for the development of antifungal agents. Furthermore, future investigations that exploit such important metabolic intermediates will further deepen our basic understanding of the molecular mechanisms underlying the establishment of fungal blast disease in important cereal crops.

15.
Oncol Lett ; 18(1): 145-152, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31289483

RESUMO

Gastric cancer (GC) is one of the most common types of malignant tumor. Due to the lack of effective drugs and the emergence of chemotherapy resistance, patients with GC exhibit a poor prognosis and low survival rate. MicroRNAs (miRNAs/miRs) serve an important role in drug resistance of different types of cancer. They may be suitable for use as biomarkers in the diagnosis, treatment and prognosis of tumors. The present study aimed to investigate the molecular mechanism underlying the ability of miR-200c-3p to reverse drug resistance in a SGC7901/DDP GC cell line, particularly its effects on the ERCC excision repair 3, TFIIH core complex helicase subunit (ERCC3) and ERCC excision repair 4, endonuclease catalytic subunit (ERCC4) proteins in the nucleotide excision repair (NER) pathway. Reverse transcription-quantitative polymerase chain reaction demonstrated that miR-200c-3p expression in cisplatin-resistant SGC7901/DDP cells was lower than in parental SGC7901 cells, whereas the protein expression levels of ERCC3 and ERCC4 in these cells were higher by western blot analysis. In SGC7901/DDP-derived miR-200c-3p overexpressing cells, ERCC3 expression, ERCC4 expression and cisplatin resistance were decreased compared with in parental SGC7901/DDP cells and SGC7901/DDP-derived vector control cells. In SGC7901-derived miR-200c-3p knockdown cells, ERCC3 expression, ERCC4 expression and cisplatin resistance were increased compared with in parental SGC7901 cells and SGC7901-derived vector control cells. In conclusion, overexpression of miR-200c-3p may reverse drug resistance in the SGC7901/DDP GC cell line via downregulation of ERCC3 and ERCC4, which suggested this may be part of a mechanism involving the NER pathway.

16.
Biosci Rep ; 39(7)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31262976

RESUMO

Uterine leiomyoma is the most common benign smooth muscle tumor of uterus in women of reproductive age, with a high lifetime incidence. Nowadays, the exploration on the pharmacotherapies, such as progesterone receptor antagonist (PRA) requires more attention. Hence, the current study aimed to examine whether mifepristone, a PRA, influences the autophagy and apoptosis of uterine leiomyoma cells. Primary uterine leiomyoma cells were collected from 36 patients diagnosed with uterine leiomyoma to establish PR-M-positive (PR-M[+]) cells. The lentiviral vector overexpressing or silencing PR-M was subsequently delivered into one part of PR-M(+) cells in order to evaluate the role of PR-M in PR-M(+) cells. The results obtained revealed that cell viability was increased, while cell autophagy and apoptosis were diminished in the PR-M(+) cells treated with overexpressed PR-M, whereby the Bcl-2 level was elevated and the level of Beclin1 was reduced. An opposite trends were identified following treatment with knockdown of PR-M. Mifepristone at different concentrations (low, moderate, or high) was then applied to treat another part of the PR-M(+) cells. Mifepristone was identified to promote cell autophagy and apoptosis, decrease Bcl-2 level and increase Beclin1 level, accompanied by weakened interaction between Bcl-2 and Beclin1. Moreover, these effects of mifepristone on PR-M(+) cells were enhanced with increasing of the concentration. Taken together, the present study present evidence indicates the ability of PRA to regulate the Bcl-2/Beclin1 axis, ultimately promoting the autophagy and apoptosis of uterine leiomyoma cells, highlighting that PRA serves as a promising therapeutic target for the treatment of uterine leiomyoma.

17.
Cancer Sci ; 110(9): 2760-2772, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31325400

RESUMO

Long noncoding RNAs (lncRNAs) are emerging as key regulators in cancer initiation and progression. TP53TG1 is a recently identified lncRNA and several studies have shown that TP53TG1 may play the role of tumor suppressor gene or oncogene in different tumors. Nevertheless, the involvement of TP53TG1 in carcinogenesis of pancreatic ductal adenocarcinoma (PDAC) has not been characterized. In our studies, we identified that TP53TG1 was highly expressed in PDAC and was a novel regulator of PDAC development. Knockdown of TP53TG1 inhibited proliferation, induced apoptosis, and decreased migration and invasion in PDAC cells, whereas enhanced expression of TP53TG1 had the opposite effects. Mechanistically, TP53TG1 could directly bind to microRNA (miR)-96 and effectively function as a sponge for miR-96, thus antagonizing the functions of miR-96 and leading to derepression of its endogenous target KRAS, which is a core oncogene in the initiation and maintenance of PDAC. Taken together, these observations imply that TP53TG1 contributes to the growth and progression of PDAC by acting as a competing endogenous RNA (ceRNA) to competitively bind to miR-96 and regulate KRAS expression, which highlights the importance of the complicated miRNA-lncRNA network in modulating the progression of PDAC.


Assuntos
Carcinoma Ductal Pancreático/genética , Proteínas de Ligação a DNA/metabolismo , MicroRNAs/antagonistas & inibidores , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , RNA Longo não Codificante/metabolismo , Carcinogênese/genética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , RNA Longo não Codificante/genética
18.
Mol Cell ; 75(4): 791-806.e8, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31303470

RESUMO

YAP/TEAD are nuclear effectors of the Hippo pathway, regulating organ size and tumorigenesis largely through promoter-associated function. However, their function as enhancer regulators remains poorly understood. Through an in vivo proximity-dependent labeling (BioID) technique, we identified YAP1 and TEAD4 protein as co-regulators of ERα on enhancers. The binding of YAP1/TEAD4 to ERα-bound enhancers is augmented upon E2 stimulation and is required for the induction of E2/ERα target genes and E2-induced oncogenic cell growth. Furthermore, their enhancer binding is a prerequisite for enhancer activation marked by eRNA transcription and for the recruitment of the enhancer activation machinery component MED1. The binding of TEAD4 on active ERE-containing enhancers is independent of its DNA-binding behavior, and instead, occurs through protein-tethering trans-binding. Our data reveal a non-canonical function of YAP1 and TEAD4 as ERα cofactors in regulating cancer growth, highlighting the potential of YAP/TEAD as possible actionable drug targets for ERα+ breast cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias da Mama/metabolismo , Proteínas de Ligação a DNA/metabolismo , Elementos Facilitadores Genéticos , Estrogênios/farmacologia , Proteínas Musculares/metabolismo , Proteínas de Neoplasias/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Genética/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteínas de Ligação a DNA/genética , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Células MCF-7 , Subunidade 1 do Complexo Mediador/genética , Subunidade 1 do Complexo Mediador/metabolismo , Camundongos , Camundongos Nus , Proteínas Musculares/genética , Proteínas de Neoplasias/genética , Fatores de Transcrição/genética
20.
Mikrochim Acta ; 186(7): 447, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31197573

RESUMO

A sensitive and rapid fluorometric "switch on" assay is described for the detection of microRNA-21. It is based on the use of a fluorescence resonance energy transfer pair consisting of lysozyme-modified gold nanoclusters (Lys-Au NCs) and carbon nanotubes (CNTs). The Lys-Au NCs can be synthesized by a microwave-assisted technique within 2.5 min. They were modified with the ss-DNA probe (a 22-mer) for microRNA-21. Once the ss-DNA associates with the CNTs due to π stacking, the orange-red fluorescence (with excitation/emission peaks at 500/610 nm) is quenched. Nevertheless, the quenched fluorescence can be recovered after addition of microRNA-21 because of the stronger affnity between ss-DNA and microRNA-21. On the basis of the fluorescence recovery at 610 nm caused by microRNA-21, the latter can be quantified in the 0.01 to 100 nM concentration range, with a 36 pM detection limit. The method was applied to the determination of microRNA-21 in spiked serum with recoveries ranging from 98.6% to 110.0%. It also enables normal and cancer cells to be differentiated by direct imaging of intracellular microRNA-21. Graphical abstract A sensitive "switch on" FRET-based fluorometric assay for microRNA-21 is described. It is based on the use of  lysozyme-modified gold nanoclusters (Lys-Au NCs) and carbon nanotubes (CNTs) as energy donor and energy acceptor, respectively.

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