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1.
Chemosphere ; 251: 126440, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32169699

RESUMO

Carbon dots (CDs) are an emerging fluorescent nano-imaging probe due to their unique characteristics, such as good conductivity, carbon-based chemical composition, and photochemical stability, which sets up the potential of outperforming the classic metal-based quantum dots (QDs). It is a timely effort to proactively investigate the biocompatibility feature of CDs with a view to safely utilize this emerging nanomaterial in biological systems. In this study, we assessed the safety profile of an in-house synthesized CDs in hepatocyte-like Hepa 1-6 cells, which represents an important target organ for CDs exposure through either particle uptake and/or accumulation and elimination from primary exposure sites post particle administration. We not only demonstrated a dose- and time-dependent compromised cell viability, but also observed the induction of autophagy at high concentration (i.e. 400 µg mL-1), authenticated by the conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II. We attributed these changes as the protective mechanism by which the cells used to compensate for CDs-induced apoptosis and cytotoxicity. The involvement of autophagy was further confirmed because the cytotoxicity profile can be increased or reduced by the use of 3-MA (autophagy inhibitor) and NAC (ROS inhibitor), respectively. Collectively, our findings revealed dose-dependent moderate cytotoxicity in Hepa 1-6 cells. Mechanistic understanding of autophagy during the cellular process revealed the homeostasis when liver cells deal with CDs as an external insult.

2.
Water Res ; 174: 115638, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32145555

RESUMO

Microcystin-leucine-arginine (MC-LR), a cyclic potentially carcinogenic hepatotoxin, occurs frequently in aquatic habitats worldwide and seriously threatens ecosystem and public health. Limited effectiveness of physicochemical treatments to remove MC-LR from drinking water has led to a search for alternative cost-effective and environment friendly biodegradation strategies. Obtaining MC-degrading bacteria and understanding their MC-degrading mechanisms are outstanding challenges. Here, a novel indigenous bacterium named Sphingopyxis sp. YF1 with a high efficient capacity for MC-degradation was successfully isolated from eutrophic Lake Taihu. Through integrating mass spectrometer and multi-omics analyses accompanied by functional verification of certain genes and proteins, a complete MC-degradation pathway was firstly identified, in which MC-LR was sequentially degraded into linearized MC-LR, tetrapeptide, Adda, phenylacetic acid, and finally potential product CO2. Some specific proteins such as microcystinase, linearized-microcystinase, tetrapeptidease and PAAase responsible for this pathway were identified. This study pioneeringly demonstrated that MC-LR can be completely degraded through natural remediation processes and revealed a significant potential for MC-LR biodegradation in both natural environment and engineered systems.


Assuntos
Microcistinas , Sphingomonadaceae , Biodegradação Ambiental , Ecossistema
3.
Toxins (Basel) ; 12(3)2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32183408

RESUMO

Microcystins (MCs), which are produced by harmful cyanobacteria blooms, pose a serious threat to environmental health. However, the effect of MCs on the bacterial community under anaerobic conditions is still unclear. This study examined the dynamic changes of MC-degrading capacity, metabolic activity, and structure of the bacterial community in lake sediment repeatedly treated with 1 mg/L microcystin-LR (MC-LR) under anaerobic conditions. The results showed that the MC-degrading capacity of the bacterial community was increased nearly three-fold with increased treatment frequency. However, the metabolic profile behaved in exactly opposite trend, in which the overall carbon metabolic activity was inhibited by repeated toxin addition. Microbial diversity was suppressed by the first addition of MC-LR and then gradually recovered. The 16S amplicon sequencing showed that the dominant genera were changed from Exiguobacterium and Acinetobacter to Prosthecobacter, Dechloromonas, and Agrobacterium. Furthermore, the increase in the relative abundance of Dechloromonas, Pseudomonas, Hydrogenophaga, and Agrobacterium was positively correlated with the MC-LR treatment times. This indicates that they might be responsible for MC degradation under anaerobic conditions. Our findings reveal the relationship between MC-LR and the sediment bacterial community under anaerobic conditions and indicate that anaerobic biodegradation is an effective and promising method to remediate MCs pollution.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32024182

RESUMO

Benzene, a commonly used chemical, has been confirmed to specifically affect the hematopoietic system as well as overall human health. PTP4A3 is overexpressed in leukemia cells and is related to cell proliferation. We previously found that HIF-1alpha was involved in benzene toxicity and PTP4A3 may be the target gene of HIF-1alpha via ChIP-seq. The aim of this study is to confirm the relationship between HIF-1alpha and PTP4A3 in benzene toxicity, as well as the function of PTP4A3 on cell toxicity induced by 1,4-benzoquinone (1,4-BQ). Our results indicate that HIF-1alpha could regulate PTP4A3 with in vivo and in vitro experiments. A cell line with suppressed PTP4A3 was established to investigate the function of PTP4A3 in 1,4-BQ toxicity in vitro. The results revealed that cell proliferation inhibition was more aggravated in PTP4A3 low-expression cells than in the control cells after 1,4-BQ treatment. The relative oxygen species (ROS) significantly increased in cells with inhibited PTP4A3, while the rise was inferior to the control cells at the 20 µM 1,4-BQ group. An increase in DNA damage was seen in PTP4A3 down-regulated cells at the 10 µM 1,4-BQ group, whereas the results reversed at the concentration of 20 µM. Moreover, the apoptosis rate increased higher in down-regulated PTP4A3 cells after 1,4-BQ exposure. In addition, PI3K/AKT pathway was significantly restrained in cells with inhibited PTP4A3 after 1,4-BQ treatment. Our results indicate that HIF-1alpha may regulate PTP4A3 to be involved in benzene toxicity. Inhibition of PTP4A3 could aggravate cell proliferation suppression and apoptosis by regulating PI3K/AKT pathway after 1,4-BQ treatment.

5.
Sci Total Environ ; 705: 135879, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31972927

RESUMO

The gut microbiota comprises a multispecies microbial community and is essential for maintaining health. Benzene is a widespread environmental and occupational pollutant that mainly causes blood and bone marrow abnormalities. However, the effects of benzene on gut microbiota and metabolism have not yet been investigated. In this study, C57BL/6 mice were exposed to 0, 6, 30 and 150 mg/kg benzene by subcutaneous injection for 30 days. We observed that white blood cell levels significantly decreased in the three benzene exposure groups, while red blood cell and hemoglobin levels were only changed remarkably in 30 and 150 mg/kg benzene-treated mice. The results of 16S rRNA sequencing showed that benzene exposure altered the overall structure of the gut microbial communities. In addition, significant enrichments of Actinobacteria (p < .05) at the phylum level and Helicobacter at the genus level were observed in the cecal contents and feces of mice exposed to 150 mg/kg benzene. Moreover, there was a significant negative correlation between Actinobacteria abundance and basic blood indicators, including white blood cell, red blood cell, and hemoglobin levels. Furthermore, according to LC-MS analysis, a total of 42 cecal metabolites were significantly altered by 150 mg/kg benzene. Several metabolic pathways were significantly influenced by benzene exposure, including cysteine and methionine metabolism, porphyrin and chlorophyll metabolism, steroid biosynthesis, aminoacyl-tRNA biosynthesis, and arginine and proline metabolism. In summary, this study demonstrated that benzene exposure causes dysbiosis of the gut microbiota and metabolic disorder in mice.

6.
Environ Pollut ; 256: 113444, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31676094

RESUMO

Microcystis blooms and their secondary metabolites microcystins (MCs) occurred all over the world, which have damaged aquatic ecosystems and threatened public health. Techniques to reduce the Microcystis blooms and MCs are urgently needed. This study aimed to investigate the algicidal and inhibitory mechanisms of a red pigment prodigiosin (PG) against the growth and MC-producing abilities of Microcystis aeruginosa (M. aeruginosa). The numbers of Microcystis cells were counted under microscope. The expression of microcystin synthase B gene (mcyB) and concentrations of MCs were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme linked immunosorbent assay (ELISA) methods, respectively. The inhibitory effects of PG against M. aeruginosa strain FACHB 905 with 50% algicidal concentration (LC50) at 120 h was 0.12 µg/mL. When M. aeruginosa cells exposed to 0.08 µg/mL, 0.16 µg/mL, 0.32 µg/mL PG, the expression of mcyB of M. aeruginosa was down-regulated 4.36, 8.16 and 18.51 times lower than that of the control at 120 h. The concentrations of total MC (TMC) also were 1.66, 1.72 and 5.75 times lower than that of the control at 120 h. PG had high algicidal effects against M. aeruginosa, with the activities of superoxide dismutase (SOD) initially increased and then decreased after 72 h, the contents of malondialdehyde (MDA) increase, the expression of mcyB gene down-regulation, and MCs synthesis inhibition. This study was first to report the PG can simultaneously lyse Microcystis cells, down-regulate of mcyB expression and inhibit MCs production effectively probably due to oxidative stress, which indicated PG poses a great potential for regulating Microcystis blooms and MCs pollution in the environment.


Assuntos
Desinfetantes/toxicidade , Microcystis/efeitos dos fármacos , Prodigiosina/toxicidade , Ecossistema , Malondialdeído/metabolismo , Microcistinas/metabolismo , Microcystis/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
7.
J Cell Biochem ; 121(4): 2889-2900, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31692042

RESUMO

Lung cancer is one of the deadliest cancers worldwide. To increase the survival rate of lung cancer, it is necessary to explore specific prognosis markers. More and more evidence finds that noncoding RNA is closely associated with the survival of lung cancer, and cancer stem cells (CSCs) also play a significant role in the progress of lung cancer. The objective of this study is to find CSLCs genes that affect the prognosis of lung cancer. The differential expression of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), messenger RNAs (mRNAs) in the Cancer Genome Atlas (TCGA) database and differential expression data from microarray of CD326+ and CD326- A549 cell are intersected to identify stable and consistent expression genes (2 lncRNAs, 15 miRNAs, and 134 mRNAs). The intersection of lncRNAs and miRNAs is analyzed by univariate and multivariate Cox regression to obtained prognostic genes. Two miRNAs (miR-30b-5p and miR-29c-3p) are significantly correlated with the overall survival rate. Then using these two miRNAs to construct a risk score model as a prognosis signature of lung cancer. Subsequently, we analyzed the association between two miRNAs and clinical information of lung cancer patients, of which T stage, Neoplasm cancer and risk score (P < .05) can be used as independent prognostic indicators of lung cancer. Finally, target genes of 2 miRNAs and 134 mRNAs were annotated with Gene Ontology and analyzed with Kyoto Encyclopedia of Genes and Genomes pathway, and verified with the GEO database. In summary, this study illustrates the role of miRNAs in the promotion of lung cancer by CSCs, which is important to find molecular biomarkers of lung cancer.

8.
J Cell Physiol ; 235(1): 548-562, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31232471

RESUMO

Accumulating evidence implies that N6-methyladenosine (m6A) methylation participated in the tumorigenesis of gastric cancer (GC). Here we synthetically analyzing the prognostic value and expression profile of seven m6A methylation-relevant genes through silico analysis of sequencing data downloaded from The Cancer Genome Atlas, Kaplan-Meier plotter, and Gene Expression Omnibus database. We explored the methyltransferase-like 3 (METTL3) expression in GC cell line and tumor tissues by reverse transcription quantitative polymerase chain reaction and western blot analysis. The m6A methylation status of total RNA was measured by m6A RNA methylation quantification kit. Small interfering RNA was used to establish METTL3 knockdown cell lines. We also measure the proliferation and migration capability GC cell. Furthermore, we detect the epithelial cell mesenchymal transition marker and m6A methylation level after METTL3 knock down. Our result revealed that METTL3 was significantly increased in GC tissues compared with control in big crowd data sets. Survival analysis showed that METTL3 serve as a poor prognostic factor for GC patients. The expression level of METTL3 gradually increased with the progress of tumor stage and grade. GFI1 is an important transcription factor associated with METTL3. We verified the up-trend of METTL3 in messenger RNA and protein expression and observed a significant increase in the m6A methylation status of total RNA in the GC cells and tissues. METTL3 knockdown inhibited total RNA m6A methylation level, as well as cell proliferation and migration capacity. Moreover, METTL3 knockdown decreased α-smooth muscle actin. Taken together, our finding revealed that m6A methylation writer METTL3 serve as an oncogene in tumorigenesis of GC.

9.
Environ Sci Pollut Res Int ; 26(34): 34754-34774, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31696427

RESUMO

Recently, there has been increased studies in noise-induced hearing loss (NIHL). We aimed to make an overview of research trends and genetic polymorphisms for NIHL from 2009 to 2018 with VOSviewer software. A total of 2391 papers were identified for research trends analysis in NIHL and 33 studies identified for a brief review of genetic polymorphisms in human NIHL. The number of publications has been increasing over the past decade. The journal Hearing Research published the most articles (218). The USA contributed the largest number of papers (1042; 43.58%), with the most citations (18,987) and the highest H-index (60). The University of Washington was the most contributive institution. Liberman MC published the most articles (32), and Kujawa SG possessed the highest co-citations (584). Except for high-frequency keywords identified by the software, "prevalence," "oxidative stress," "hair cells," and "cochlear implant" were also the latest research frontiers. HSPA1A rs1043618, HSPA1L rs2227956, PON2 rs12026 and rs7785846, SOD2 rs2855116, KCNE1 rs2070358, KCNQ4 rs34287852, GJB2 rs3751385, PCDH15 rs7095441 and rs11004085, GRHL2 rs1981361, ITGA8 rs10508489, MYH14 rs667907, and POU4F3 rs891969 were the research hotspots and were replicated in independent samples. Inflammation response underlying NIHL has emerged and should be considered as a pioneering field in the future for the prevention of NIHL and conservation of hearing.


Assuntos
Predisposição Genética para Doença/epidemiologia , Perda Auditiva Provocada por Ruído/genética , Proteínas de Ligação a DNA/genética , Proteínas de Homeodomínio , Humanos , Polimorfismo de Nucleotídeo Único , Fator de Transcrição Brn-3C , Fatores de Transcrição/genética
10.
Anal Chem ; 91(24): 15804-15810, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31718146

RESUMO

Because of the extremely low solubility of gas pollution, elucidating the pathogenetic mechanism between air pollution and the lung inflammatory response has remained a significant challenge. Here, we develop a bioinspired nanoporous membrane (BNM) with a three-phase interface as a gas exposure model that mimicks the airway mechanism, gas molecules contacting with alveolar cells directly, enabling high cell viability and sensitive inflammatory response analysis. Specifically, the top side of the porous anodic alumina (PAA) membrane was in contact with the medium for cell culture, and the bottom side contacted the gas phase directly for gas exposure. Compared with the two-phase interface, the viability of cells on the BNM was enhanced up to 3-fold. Additionally, results demonstrated that the inflammatory responses of cells stimulated by gas pollution (formaldehyde and benzene as models) from the gas phase were more obvious than those induced by gas pollution from solution, especially the increment of interleukin-2 (IL-2), IL-6, and tumor necrosis factor α (TNF-α), which was almost 2 times greater than that induced by gas pollution from solution. Furthermore, an enzyme inhibitor was introduced to evaluate potential applications of the BNM.

11.
Chemosphere ; 235: 288-296, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31260869

RESUMO

The Huai'an area in Jiangsu Province of East China is an endemic region of esophageal cancer (EC). The regional heterogeneity of EC suggests that the levels of potential carcinogens might vary throughout the environment. It has been suggested that the most likely carcinogens related to EC are a group known as the N-nitrosamines. In this study, we measured the concentrations of nine nitrosamines in drinking water and human urine in two areas in China, one with a high incidence of EC (Huai'an) and one with a low incidence (Nanjing). Among the nine target analytes, N-nitrosodi-n-propylamine (NDPA), N-nitrosodibutylamine (NDBA), N-nitrosopyrrolidine (NPyr), N-nitrosodiethylamine (NDEA) and N-nitrosomorpholine (NMor) occurred at higher concentrations in drinking water in the high incidence area. Inhabitants from the high incidence area also had urinary excretions with significantly higher concentrations of NDEA, NDBA, N-nitrosopiperidine (NPip) and N-nitrosodiphenylamine (NDPhA). These findings indicated that people in the high EC incidence area were exposed to higher levels of nitrosamines. However, the association between the incidence of EC and nitrosamines exposure will need to be evaluated in more detail.


Assuntos
Carcinógenos/análise , Água Potável/química , Neoplasias Esofágicas/epidemiologia , Nitrosaminas/análise , China , Neoplasias Esofágicas/induzido quimicamente , Neoplasias Esofágicas/etiologia , Humanos , Incidência , Nitrosaminas/urina
12.
Cancer Manag Res ; 11: 6201-6214, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308755

RESUMO

Background: Esophageal squamous cell carcinoma (ESCC) is the fourth most common cause of cancer death in China. Long noncoding RNAs have emerged as critical regulators in cancer. Long intergenic noncoding RNA-p21, a kind of Long noncoding RNAs, LincRNA-p21 have been discussed dysregulated in several cancers, but its role in ESCC remains unknown. This study investigated the role of LincRNA-p21 in ESCC. Materials and methods: The LincRNA-p21 expression level and its association with esophageal cancer was determined in 64 tumor tissues of esophageal squamous cell carcinoma patients and cells using quantitative real-time reverse transcription PCR. Fluorescence in situ hybridization of single-RNA molecular probes was used to determine subcellular localization of LincRNA-p21. CCK8 and EdU assays were used for proliferation assay, flow cytometry was performed for apoptosis and cell-cycle distribution, and 24-well Mill cell chamber was made for measuring the abilities of migration and invasion after transfected with lentivirus-expressing LincRNA-p21 in EC109 cells. Then, quantitative real-time reverse transcription PCR and Western blot detected the expression of p21. Further, UC2288, an inhibitor of p21, was used to decrease the level of p21, and flow cytometry was used to detect cell cycle. Finally, screening for differential pathways from microarray analysis and expression of p53 and cyclin D were detected by Western blot. Results: LincRNA-p21 expression level was remarkably lower in tumor tissues versus nontumor tissues and lower in EC109 cells versus Het-1A cells. Statistical analysis found that LincRNA-p21 might enhance the risk of ESCC. We observed that LincRNA-p21 was expressed both in the nucleus and cytoplasm, and a larger proportion of LincRNA-p21 was observed in the cytoplasm. The results demonstrated that upregulating the expression of LincRNA-p21 could inhibit cell proliferation, migration, invasion, and the transition of cell cycle from G1 and promoted apoptosis of EC109. Then, we found that LincRNA-p21 promotes the expression of p21. Decreasing the level of p21 revealed that cell-cycle arrest was restored. Pathway analysis found p53 pathway was downregulated, and upregulation of LincRNA-p21 inhibited the expression of cyclin D. Conclusion: Our study suggests that LincRNA-p21 plays as a tumor inhibitor in ESCC development and LincRNA-p21 might induce G1 arrest through p53 signal pathway.

13.
Toxicol In Vitro ; 60: 107-115, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31077745

RESUMO

Prodigiosin contains a tripyrrole skeleton and shows impressive anticancer potential in multiple cell lines. Numerous studies have been conducted on prodigiosin-induced apoptosis and the related mechanisms. However, few reports have considered the effects of prodigiosin on autophagy and the relationship between apoptosis and autophagy. Here, we examined whether prodigiosin affected apoptosis and autophagy through the extracellular signal-regulated (ERK) signaling pathway in K562 cells, employing cell proliferation, flow cytometry, caspase activity, and western blot analyses. Inhibition of the ERK signaling pathway with PD184352 was conducted to verify the role of this pathway on prodigiosin-mediated processes. Our findings revealed that prodigiosin inhibited the proliferation of K562 cells, increased reactive oxygen species (ROS), induced apoptosis and inhibited autophagy in K562 cells. Additionally, the ROS scavenger, N-Acetyl-L-cysteine (NAC), partially prevented prodigiosin-induced apoptosis but did not reduce prodigiosin-inhibited autophagy in K562 cells. Furthermore, prodigiosin treatment in K562 cells reduced the phosphorylation of c-Jun N-terminal kinases (JNKs) and P38, and activated ERK signaling pathway. When ERK1/2 phosphorylation was blocked by PD184352, prodigiosin-induced apoptosis and the inhibition of autophagy decreased significantly. Taken together, these results demonstrated that the ERK signaling pathway was involved in prodigiosin-induced apoptosis and prodigiosin-inhibited autophagy.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Prodigiosina/farmacologia , Caspases/metabolismo , Proliferação de Células/efeitos dos fármacos , Humanos , Células K562 , Espécies Reativas de Oxigênio/metabolismo
14.
PeerJ ; 7: e6761, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31065456

RESUMO

Background: Cervical cancer (CC) is a common gynecological malignancy in women worldwide. Evidence suggests that long non-coding RNAs (lncRNAs) can be used as biomarkers in patients with CC. However, prognostic biomarkers for CC are still lacking. The aim of our study was to find lncRNA biomarkers which are able to predict prognosis in CC based on the data from The Cancer Genome Atlas (TCGA). Methods: The patients were divided into three groups according to FIGO stage. Differentially expressed lncRNAs were identified in CC tissue compared to adjacent normal tissues based on a fold change >2 and <0.5 at P < 0.05 for up- and downregulated lncRNA, respectively. The relationship between survival outcome and lncRNA expression was assessed with univariate and multivariate Cox proportional hazards regression analysis. We constructed a risk score as a method to evaluate prognosis. We used receiver operating characteristic (ROC) curve and the area under curve (AUC) analyses to assess the diagnostic value of a two-lncRNA signature. We detected the expression levels of the two lncRNAs in 31 pairs of newly diagnosed CC specimens and paired adjacent non-cancerous tissue specimens, and also in CC cell lines. Finally, the results were statistically compared using t-tests. Results: In total, 289 RNA sequencing profiles and accompanying clinical data were obtained. We identified 49 differentially expressed lncRNAs, of which two related to overall survival (OS) in CC patients. These two lncRNAs (ILF3-AS1 and RASA4CP) were found together as a single prognostic signature. Meanwhile, the prognosis of patients with low-risk CC was better and positively correlated with OS (P < 0.001). Further analysis showed that the combined two-lncRNA expression signature could be used as an independent biomarker to evaluate the prognosis in CC. qRT-PCR results were consistent with TCGA, confirming downregulated expression of both lncRNAs. Furthermore, upon ROC curve analysis, the AUC of the combined lncRNAs was greater than that of the single lncRNAs alone (0.723 vs 0.704 and 0.685), respectively; P < 0.05. Conclusions: Our study showed that the two-lncRNA signature of ILF3-AS1 and RASA4CP can be used as an independent biomarker for the prognosis of CC, based on bioinformatic analysis.

15.
J Cell Biochem ; 120(8): 13912-13923, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30963622

RESUMO

Lung squamous cell carcinoma (LUSC) is one of the main histological types of lung cancer with high mortality. The role of microRNA-486-5p in LUSC remains unclear. In the current study, the aim was to explore miR-486-5p expression and its role in LUSC. The miR-486-5p expression was significantly low-expressed in patients with LUSC from The Cancer Genome Atlas database, which was further confirmed in the Gene Expression Omnibus database, patients' tissues, different cell lines by quantitative real-time polymerase chain reaction, and the high-throughput gene sequencing data of lung tissues of mice after a long-term B(a)P exposure. The meta-analysis was performed to evaluate the expression and diagnosis power of miR-486-5p (standard mean difference = -2.25; 95% confidence interval: -3.47 to -1.03; P = 0.0003; area under curve = 0.9082). Functional enrichment analysis revealed the potential function of miR-486-5p in LUSC using gene set enrichment analysis and clusterProfiler package in R software. At last, the hub genes (PTEN, TEK, PIK3R1, PPM1B, SMAD2, and SPTA1) of miR-486-5p were verified. In conclusion, miR-486-5p may be a LUSC antioncogene, playing an important role to serve as a biomarker in LUSC.

16.
Int J Nanomedicine ; 14: 993-1009, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30799918

RESUMO

Purpose: Protein adsorption onto nanoparticles in the form of protein corona, affects properties of nanomaterials and their behavior in the biological milieu. This study aims at exploring the effects of multiwalled carbon nanotubes (MWCNTs) surface chemistry on bovine serum albumin (BSA) and immunoglobulin G (IgG), including their adsorption behavior and spatial configurations, as well as the impact on cellular uptake, cytotoxicity, and cellular responses. Methods: Three types of MWCNTs (pristine MWCNTs, MWCNTs-COOH, and MWCNTs-PEG) were synthesized by classical chemical reduction. The size, morphology, hydrodynamic size, and zeta potential were characterized using transmission electron microscopy and dynamic light scattering. MWCNTs were exposed to BSA and IgG solutions, then the amount of MWCNT absorption was performed by bicinchoninic acid assay, and the effects were assessed by utilizing fluorescence spectroscopy, circular dichroism (CD) spectroscopy. Quantitative measurement of MWCNTs uptake with or without protein corona was performed as turbidity method. CCK assay and a microdilution method were performed to evaluate the effects of protein corona on cytotoxicity and pro-inflammatory cytokines release. Results: The BSA and IgG adsorption capacities of MWCNTs followed the order pristine MWCNTs>MWCNTs-COOH and MWCNTs-PEG. MWCNT binding can cause fluorescence quenching and conformational changes in BSA and IgG, indicating that both the physicochemical properties of MWCNTs and protein properties play critical roles in determining their adsorption behavior. Further study showed time-dependent increases in MWCNT cellular uptake and internalization. Hydrophobicity is the major factor increasing cellular uptake of pristine MWCNTs, but a protein corona enriched with dysoposnins is the main factor reducing uptake of MWCNT-COOH by RAW264.7 cells. The cytotoxicity and pro-inflammatory response related to physicochemical properties of MWCNTs, and frustrated phagocytosis is a key initiating event in the pro-inflammatory response of MWCNT-exposed macrophages. Conclusion: These findings shed light on how functionalized MWCNTs interact with protein coronas and provide useful insight into the dramatic effect of protein coronas on different functionalized MWCNTs. These events affect cellular uptake and cytotoxicity, which could inform how to enhance MWCNT biocompatibility and develop approaches for managing MWCNT hazards.


Assuntos
Endocitose , Nanotubos de Carbono/química , Coroa de Proteína/química , Adsorção , Animais , Morte Celular/efeitos dos fármacos , Dicroísmo Circular , Citocalasina D/farmacologia , Citocinas/biossíntese , Endocitose/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Imunoglobulina G/química , Mediadores da Inflamação/metabolismo , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Nanotubos de Carbono/toxicidade , Nanotubos de Carbono/ultraestrutura , Fagocitose/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Estrutura Secundária de Proteína , Células RAW 264.7 , Soroalbumina Bovina/química , Espectrometria de Fluorescência , Propriedades de Superfície
17.
Environ Sci Pollut Res Int ; 26(11): 11279-11287, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30796669

RESUMO

Chlordecone (CLD), also named Kepone, is a synthetic organochlorine pesticide. As one of the common persistent organic pollutants (POPs) in nature, CLD has a profound impact on the environment and human health. The study aims to investigate the reproductive toxicity effects of CLD on male Caenorhabditis elegans and on progeny. L1-stage male nematodes were exposed to the control group (M9 solution) and four dose groups (0.02, 0.2, 2, and 20 µg/L). After exposure for 48 h, the male nematodes were picked to mating experiment and progeny experiment that the number of progeny and the time of observation in male parent and in F1 generation were counted; the number of germ cells and the number of sperm in the meiotic division of male nematodes were counted by staining with dimercaptophenyl hydrazine (DAPI), and the nematode gland area was observed under the bright field of the microscope. In male nematodes, the results showed that a number of progeny were 351.20 ± 31.40, 321.60 ± 24.70, 307.30 ± 19.30, 240.10 ± 27.60, and 227.90 ± 22.70 (P < 0.05); the generation times were 55.80 ± 1.95 h, 56.40 ± 1.60 h, 56.70 ± 0.92 h, 60.80 ± 0.95 h, and 69.60 ± 1.97 h (P < 0.05); relative areas of gonad were (99.80 ± 6.27)%, (93.00 ± 1.70)%, (85.00 ± 1.70)%, (70.70 ± 9.81)%, and (60.00 ± 5.23)% (P < 0.05); DAPI staining results showed the number of germ cells in meiosis area were 191.00 ± 10.97, 181.10 ± 15.56, 177.00 ± 9.20, 147.50 ± 10.56, and 139.30 ± 23.79 (P < 0.05); the sperm numbers were 335.60 ± 21.31, 308.60 ± 19.60, 306.00 ± 11.23, 260.10 ± 27.41, and 255.00 ± 3.72 (P < 0.05). In the F1 generation, the progeny numbers were 328.10 ± 22.28, 167.50 ± 15.30, 150.00 ± 13.65, 131.30 ± 18.40, and 130.20 ± 16.17 (P < 0.05); the generation times were 55.50 ± 2.36, 71.10 ± 0.97, 70.90 ± 0.52, 74.10 ± 2.07, and 73.90 ± 1.35 h (P < 0.05). The groups are grouped in order as M9 solution, 0.02, 0.2, 2, and 20 µg/L. The results revealed that CLD caused decrease in progeny number, relative area of gonad, number of germ cells, and sperm number and prolonged the generation time in the male nematode. In offspring grown up without CLD, the effect of CLD on generation time and sperm number can still be observed on offspring. In conclusion, CLD induces male nematode reproductive toxicity and causes defects in offspring.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/fisiologia , Clordecona/toxicidade , Praguicidas/toxicidade , Animais , Feminino , Masculino , Reprodução/efeitos dos fármacos , Comportamento Sexual Animal/efeitos dos fármacos , Contagem de Espermatozoides
18.
J Cell Biochem ; 120(1): 705-714, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30125988

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD), mainly originated in lung glandular cells, is the most frequent pathological type of lung cancer and the 5-year survival rate of LUAD patients is still very low. Therefore, we aim to identify a long noncoding RNA (lncRNA)-related signature as the sensitive and novel prognostic biomarkers. METHODS: The associations between survival outcome and the intersection of lncRNAs were obtained from The Cancer Genome Atlas (TCGA) database. By the univariate and multivariate Cox analyses, key lncRNAs were identified to construct the prognostic model. The model was estimated by survival analysis and receiver operating characteristic curve, and verified by the Kaplan-Meier (K-M) plotter and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Functional enrichment analysis was also performed. RESULTS: A four-lncRNA signature (CEBPA-AS1, GVINP1, MIR31HG, and RAET1K) was developed after Cox analysis. The power of the four-lncRNA prognostic signature was effective in the TCGA database. The results from by the K-M plotter and qRT-PCR validation were consistent with our TCGA bioinformatics results. Furthermore, Gene Ontology and pathway analysis revealed the tumorigenic and prognostic function of the four lncRNAs. CONCLUSIONS: By mining the TCGA data, we built a four-lncRNA signature, which could effectively predict prognosis of LUAD. In the future, an independent cohort is needed to validate our findings. IMPACT: The four-lncRNA signature could become potential prognostic indicator of LUAD in the future.


Assuntos
Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , RNA Longo não Codificante/genética , Transcriptoma , Adenocarcinoma de Pulmão/mortalidade , Idoso , Biomarcadores Tumorais/genética , Bases de Dados Genéticas , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Taxa de Sobrevida
19.
Toxicol In Vitro ; 55: 18-23, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30448556

RESUMO

Benzene is an environmental contaminant which causes hematological diseases. Previously, hypoxia inducible factor-1a (HIF-1a) was found to be involved in benzene-induced hematotoxicity. This study aims to explore whether overexpression of HIF-1a in K562 cell line could influence the toxicity caused by 1,4-BQ. HIF-1a overexpression K562 cell line was constructed with a lentiviral vector. Results showed that HIF-1a was significantly elevated in control K562 cells and HIF-1a overexpression cells exposed to 1,4-BQ. Compared with 1,4-BQ exposed control cells, HIF-1a overexpression blocked cell cycle at G2/M phase, remarkably reduced apoptosis and ROS level. And HIF-1a overexpression caused downregulation of Nox4 and upregulation of Bcl-2. In addition, the lactic acid (LD)/pyruvic acid (PA) ratio was significantly higher in HIF-1a overexpression cells than that in control cells at the same 1,4-BQ dose. Furthermore, significant increases in Glut1, Ldha, Pkm2, Pgk1, Pdk1, Pfkl, Pfkfb3 protein levels was also observed in HIF-1a overexpression cells. Overall, our results indicated that HIF-1a overexpression could alleviate ROS and apoptosis caused by 1,4-BQ through targeting Nox4, Bcl-2 and key enzymes in glycolysis.


Assuntos
Benzoquinonas/toxicidade , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Humanos , Células K562 , NADPH Oxidase 4/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
20.
Toxins (Basel) ; 10(12)2018 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-30558170

RESUMO

Microcystin-LR (MC-LR) is the most widely distributed microcystin (MC) that is hazardous to environmental safety and public health, due to high toxicity. Microbial degradation is regarded as an effective and environment-friendly method to remove it, however, the performance of MC-degrading bacteria in environmentally relevant pollution concentrations of MC-LR and the degradation pathways remain unclear. In this study, one autochthonous bacterium, Sphingopyxis sp. m6 which exhibited high MC-LR degradation ability, was isolated from Lake Taihu, and the degrading characteristics in environmentally relevant pollution concentrations were demonstrated. In addition, degradation products were identified by utilizing the full scan mode of UPLC-MS/MS. The data illustrated that strain m6 could decompose MC-LR (1⁻50 µg/L) completely within 4 h. The degradation rates were significantly affected by temperatures, pH and MC-LR concentrations. Moreover, except for the typical degradation products of MC-LR (linearized MC-LR, tetrapeptide, and Adda), there were 8 different products identified, namely, three tripeptides (Adda-Glu-Mdha, Glu-Mdha-Ala, and Leu-MeAsp-Arg), three dipeptides (Glu-Mdha, Mdha-Ala, and MeAsp-Arg) and two amino acids (Leu, and Arg). To our knowledge, this is the first report of Mdha-Ala, MeAsp-Arg, and Leu as MC-LR metabolites. This study expanded microbial degradation pathways of MC-LR, which lays a foundation for exploring degradation mechanisms and eliminating the pollution of microcystins (MCs).


Assuntos
Poluentes Ambientais/metabolismo , Microcistinas/metabolismo , Sphingomonadaceae/metabolismo , Arginina/metabolismo , Proteínas de Bactérias/genética , Biodegradação Ambiental , Leucina/metabolismo , Peptídeos/metabolismo , Sphingomonadaceae/genética , Transcriptoma
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