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1.
Stem Cell Res ; 43: 101724, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32078988

RESUMO

CUL4B gene encodes a scaffold protein that assembles the CRL4B ubiquitin ligase complex, and its mutation can causes X-Linked Mental Retardation (XLMR) emerged with intellectual deficit, delayed puberty, short stature and fine intention tremor. Here we report the generation of SDUBMSi002-A, an induced pluripotent stem cell line derived from patient with c. 1564C→T with CUL4B gene using non-integrative reprogramming technology. The iPSCs line expresses pluripotent markers, has a normal male karyotype and can differentiate into the three germ layers.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32003962

RESUMO

The second near-infrared (NIR-II, 1000-1700 nm) light-based diagnosis and therapy have received extensive attention for neoplastic disease treatments because of the fact that light in the NIR-II window possesses less photon scattering along with deeper tissue penetration than that in the NIR-I (700-950 nm) window. Herein, we present a Gd- and copper sulfide (CuS)-integrated nanogel (NG) platform for magnetic resonance (MR)/photoacoustic (PA) imaging-guided tumor-targeted photothermal therapy (PTT). In our approach, we prepared cross-linked polyethylenimine (PEI) NGs via an inverse emulsion method, modified the PEI NGs with Gd chelates, targeting ligand folic acid (FA) through a polyethylene glycol (PEG) spacer and 1,3-propanesultone, and finally loaded CuS nanoparticles (NPs) within the functional NGs. The as-synthesized Gd/CuS@PEI-FA-PS NGs with a mean size of 85 nm exhibit a good water dispersibility and protein resistance property, admirable r1 relaxivity (11.66 mM-1 s-1), excellent NIR-II absorption feature, high photothermal conversion efficiency (26.7%), and FA-mediated targeting specificity to cancer cells overexpressing FA receptor (FAR). With these properties along with the good cytocompatibility, the developed Gd/CuS@PEI-FA-PS NGs enable MR/PA dual-mode imaging-guided targeted PTT of FAR-overexpressing tumors under the irradiation of an NIR-II (1064 nm) laser. The designed Gd/CuS@PEI-FA-PS NGs may be used as a promising theranostic agent for MR/PA dual-mode imaging-guided PTT of other FAR-expressing tumors.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32033382

RESUMO

On 23 January 2020, the government of China announced a lockdown of all public transportationdeparting from Wuhan, including airports, trains, and buses [...].

4.
Chemistry ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31912555

RESUMO

Multidrug resistance (MDR) is regarded as a main obstacle for effective chemotherapy, and P-glycoprotein (P-gp)-mediated drug efflux has been demonstrated to be the key factor responsible for MDR. In this study, a novel pH-responsive hybrid drug delivery system was developed by conjugating d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), a kind of P-gp inhibitor, on the surface of laponite nanodisks to overcome MDR. The prepared LM-TPGS display excellent colloidal stability, a high encapsulation efficiency of doxorubicin (DOX), and a pH-responsive drug release profile. In vitro experiments verified that LM-TPGS/DOX could exhibit significantly enhanced therapeutic efficacy in treating DOX-resistant breast cancer cells (MCF-7/ADR) through inhibiting the activity of P-gp-mediated drug efflux and effectively accumulating DOX within cancer cells. In vivo results revealed that LM-TPGS/DOX outstandingly suppressed MCF-7/ADR tumors with low side effects. Therefore, the high drug payload, enhanced inhibition efficacy to drug-resistant cells, and low side effects make the LM-TPGS/DOX a promising nanoplatform to reverse MDR for effective chemotherapy.

5.
Environ Sci Pollut Res Int ; 27(1): 873-881, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31820237

RESUMO

Pre-oxidation in water treatment is considered an effective method to enhance the removal of algal cells and their exuded organic matters. However, pre-oxidation also alters the characteristics of algae and consequently influences disinfection processes. The existing studies mainly focused on the stationary growth phase, but little is known for the exponential and declined phases. The objectives of this study were to examine the effects of pre-ozonation on the integrity of algal cells, the release of algal organic matters, and the formation of disinfection by-products like N-nitrosodimethylamine (NDMA) from Microcystis aeruginosa (M. aeruginosa) at three growth phases. The results demonstrated that pre-ozonation was efficient to inactivate M. aeruginosa cells. The severity of M. aeruginosa cell damage increased as the ozone dosage increased from 0.5 to 2.0 mg/L. The damage of cell membranes resulted in the release of intracellular organic matters. Excitation-emission matrix spectra (EEMS) analysis indicated that ozone mainly reacted with soluble microbial products (SMP). With the increase of ozone concentration, although the trend of NDMA formation was similar for all three growth phases, more production of NDMA by algal cells was observed at the declined phase. In the post-disinfection process, chloramine showed the potential as a more suitable disinfectant than chlorination after pre-ozonation to minimize the NDMA formation. Therefore, appropriate pre-ozonation is beneficial to reduce the NDMA formation from exponential algae, while has no significant change during both stationary and declined phases.

6.
J Pathol ; 250(2): 217-230, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31650548

RESUMO

Aberrant expression of forkhead box C1 (FOXC1) promotes tumor metastasis in multiple human malignant tumors. However, the upstream modulating mode and downstream molecular mechanism of FOXC1 in metastasis of colorectal cancer (CRC) remain unclear. Herein we describe a systematic analysis of FOXC1 expression and prognosis in CRC performed on our clinical data and public databases, which indicated that FOXC1 upregulation in CRC samples was significantly associated with poor prognosis. FOXC1 knockdown inhibited migration and invasion, whereas FOXC1 overexpression caused the opposite phenotype in vitro and in vivo. Furthermore, MMP10, SOX4 and SOX13 were verified as the target genes of FOXC1 for promoting CRC metastasis. MMP10 was demonstrated as the direct target and mediator of FOXC1. Interestingly, Ser241 and Ser272 of FOXC1 were identified as the key sites to interact with p38 and phosphorylation, which were critically required for maintaining the stability of FOXC1 protein. Moreover, FOXC1 was dephosphorylated by protein phosphatase 2A and phosphorylated by p38, which maintained FOXC1 protein stability through inhibiting ubiquitination. Expression of p38 was correlated with FOXC1 and MMP10 expression, indirectly indicating that FOXC1 was regulated by p38 MAPK. Therefore, FOXC1 is strongly suggested as a pro-metastatic gene in CRC by transcriptionally activating MMP10, SOX4 and SOX13; p38 interacts with and phosphorylates the Ser241 and ser272 sites of FOXC1 to maintain its stability by inhibiting ubiquitination and degradation. In conclusion, the protein stability of FOXC1 mediated by p38 contributes to the metastatic effect in CRC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

7.
Biomed Pharmacother ; 121: 109656, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31810129

RESUMO

BACKGROUND: Dachengqi decoction (DCQD) is a classical prescription in traditional Chinese medicine (TCM). It has been used to treat abdominal pain and acute pancreatitis (AP) for thousands of years in China. OBJECTIVE: To predict the active components and signaling pathway of DCQD and to further explore the potential molecular mechanism of DCQD as a treatment of AP using network pharmacology. METHODS: Network pharmacology and bioinformatics were used to determine the active components of DCQD and its potential target in the treatment of AP. The AP model was induced by Cerulein (Cer) combined with lipopolysaccharide (LPS). The pharmacodynamic basis of DCQD in the treatment of AP was evaluated in vitro and in vivo and Western blot analysis and immunofluorescence were used to determine the molecular mechanism of DCQD. RESULTS: Screening using relevant databases and topological analysis revealed 71 active components and 535 potential target proteins in DCQD. In addition, 445 differential genes for AP were also screened. Pathway enrichment analysis, PPI network analysis and transcription factor prediction showed that DCQD played an important role in the PI3K-Akt signal pathway, and 17 DCQD monomers were found in this signal pathway. In the AP model, DCQD promoted pancreatic acinar cell apoptosis, reduction in inflammation, and regulation of the PI3K-AKT signaling pathway. DCQD inhibited the expression of p-AKT and p- NF-kB proteins in pancreatic tissue of the AP model both in vitro and in vivo. CONCLUSION: This study reveals that 17 active components of DCQD improve AP by regulating the PI3K/AKT signaling pathway and promoting apoptosis and suppressing pathological injury and inflammation.

8.
Adv Sci (Weinh) ; 6(23): 1901114, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31832310

RESUMO

Frameshift mutations frequently occur in colorectal cancer (CRC) with microsatellite instability (MSI), but the nature and biological function of many MSI-associated mutations remain elusive. Here, an MSI frameshift mutation is identified in glioma tumor suppressor candidate region gene 1 (GLTSCR1) that produces two C-terminal-truncated proteins. Additionally, GLTSCR1 is verified as a tumor suppressor that inhibits CRC metastasis. Through binding to bromodomains and the phosphorylation-dependent interaction domain of bromodomain protein 4 (BRD4) via the C-terminus, GLTSCR1 blocks oncogenic transcriptional elongation. However, truncated GLTSCR1 translocates into the cytoplasm and loses BRD4 binding domain, which induces the phosphorylation of RNA Pol II at Ser2 and dephosphorylation at Ser5, then increases oncogenic transcriptional elongation. Importantly, GLTSCR1 deficiency decreases sensitivity to bromodomain and extra terminal domain inhibitors. This study highlights the molecular mechanism of the GLTSCR1-BRD4 interaction, which is a potential therapeutic target for CRC.

9.
Stem Cell Res Ther ; 10(1): 358, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779691

RESUMO

BACKGROUND: The therapeutic potential of mesenchymal stem cells (MSCs) may be attributed partly to the secreted paracrine factors, which comprise exosomes. Exosomes are small, saucer-shaped vesicles containing miRNAs, mRNAs, and proteins. Exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) have been reported to promote angiogenesis. However, the efficacy of exosome-based therapies is still limited both in vitro and in vivo. The present study aimed to develop a new optical manipulation approach to stimulate the proangiogenic potential of exosomes and characterize its mechanism underlying tissue regeneration. METHODS: We used blue (455 nm) and red (638 nm) monochromatic light exposure to investigate the processing of stimuli. Exosomes were prepared by QIAGEN exoEasy Maxi kit and confirmed to be present by transmission electron microscopy and immunoblotting analyses. The proangiogenic activity of blue light-treated human umbilical vein endothelial cells (HUVECs), when co-cultured with hUC-MSCs, was assessed by EdU (5-ethynyl-2'-deoxyuridine) incorporation, wound closure, and endothelial tube formation assays. The in vivo angiogenic activity of blue light-treated MSC-derived exosomes (MSC-Exs) was evaluated using both murine matrigel plug and skin wound models. RESULTS: We found that 455-nm blue light is effective for promoting proliferation, migration, and tube formation of HUVECs co-cultured with MSCs. Furthermore, MSC-Exs stimulated in vivo angiogenesis and their proangiogenic potential were enhanced significantly upon blue light illumination. Finally, activation of the endothelial cells in response to stimulation by blue light-treated exosomes was demonstrated by upregulation of two miRNAs, miR-135b-5p, and miR-499a-3p. CONCLUSIONS: Blue (455 nm) light illumination improved the therapeutic effects of hUC-MSC exosomes by enhancing their proangiogenic ability in vitro and in vivo with the upregulation of the following two miRNAs: miR-135b-5p and miR-499a-3p.

10.
Stem Cell Res ; 41: 101628, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31678776

RESUMO

CUL4B gene mutation can cause intelligence deficiency 15, a syndromic form of X-linked mental retardation characterized by severe intellectual deficit associated with short stature, craniofacial dysmorphism, speech delay and impairment, tremor and gait ataxia. Here, we generated iPSCs from a Chinese patient with c.1007_1011del (p.(Ile336fs)) in CUL4B gene by reprogramming peripheral blood mononuclear cells with non-integrating vectors. The generated iPSC line (SDQLCHi015-A) expresses pluripotency markers, presents a normal karyotype and is able to differentiate into three germ layers.

11.
Biomaterials ; 225: 119539, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31622821

RESUMO

Photostimulation has been widely used in neuromodulation. However, existing optogenetics techniques require genetic alternation of the targeted cell or tissue. Here, we report that neural stem cells (NSCs) constitutionally express blue/red light-sensitive photoreceptors. The proliferation and regulation of NSCs to neuronal or glial cells are wavelength-specific. Our results showed a 4.3-fold increase in proliferation and 2.7-fold increase in astrocyte differentiation for cells under low-power blue monochromatic light exposure (455 nm, 300 µW/cm2). The melanopsin (Opn4)/transient receptor potential channel 6 (TRPC6) non-visual opsin serves as a key photoreceptor response to blue light irradiation. Two-dimensional gel electrophoresis coupled with mass spectrometry further highlighted the Jun activation domain-binding protein 1 (Jab1) as a novel and specific modulator in phototransduction pathways induced by blue light exposure. Quiescent adult NSCs reside in specific regions of the mammalian brain. Therefore, we showed that melanopsin/TRPC6 expressed in these regions and blue light stimulation through optical fibers could directly stimulate the NSCs in vivo. Upconversion nanoparticles (UCNPs) converted deep-penetrating near-infrared (NIR) light into specific wavelengths of visible light. Accordingly, we demonstrated that UCNP-mediated NIR light could be used to modulate in vivo NSC differentiation in a less invasive manner. In the future, this light-triggered system of NSCs will enable nongenetic and noninvasive neuromodulation with therapeutic potential for central nervous system diseases.

12.
J Clin Immunol ; 39(8): 795-804, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31625129

RESUMO

PURPOSE: Genome-wide association study of systemic lupus erythematosus (SLE) revealed tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) as a susceptibility gene. Here, we report a de novo mutation in TNFAIP3 in a Chinese patient with neuropsychiatric SLE (NPSLE). METHODS: Whole exome sequencing was performed for the patient and healthy members from the family. Suspected pathogenic variants were further analyzed and co-segregation was confirmed by Sanger sequencing. Real-time PCR and western blot were performed with peripheral blood mononuclear cells (PBMCs) and patient-derived T cells. Transfected HEK293T cells, human umbilical vein endothelial cells, normal human astrocytes, and microglia were used for in vitro studies. RESULTS: A de novo frameshift mutation in TNFAIP3 was found in the NPSLE patient. Western blot analysis showed activated NF-κB and mitogen-activated protein kinase pathways. Real-time PCR revealed elevated expression of pro-inflammatory cytokines. On immunoprecipitation assay, the mutant A20 altered the K63-linked ubiquitin level of TRAF6 via its ubiquitin-editing function. CONCLUSIONS: The mutant A20 may play a role in weakening the tight junction of the blood-brain barrier to cause neurologic symptoms. We report a rare variant of TNFAIP3 in a patient with NPSLE and reveal its autoimmune disease-causing mechanism in both peripheral tissues and the central nervous system.

13.
Microorganisms ; 7(10)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31597319

RESUMO

Deinococcus radiodurans adapts to challenging environments by modulating gene expression in response to oxidative stress. Recently, bacterial small noncoding RNAs (sRNAs) have been presumed to participate in the transcriptional or translational regulation of stress-responsive genes. We found 24 sRNAs that may be involved in the oxidative stress response of D. radiodurans by deep RNA sequencing. Moreover, a typical stress-inducible sRNA, IGR_3053, named OsiA, was predicted to bind to the mRNA of katA, katE, and sodC by the bioinformatics method. An osiA knockout of D. radiodurans displayed increased sensitivity to H2O2 and the decreased catalase activity and total antioxidant activity, suggesting that OsiA probably serves as a regulator in the adaptation to oxidative environments. Further microscale thermophoresis results demonstrated that OsiA can directly bind to the mRNA of katA, sodC, and katE. The stability test result of katA mRNA showed that its half-life was 2 min in the osiA mutant compared with 5 min in the wildtype(wt) strain. Our results indicated that OsiA can enhance the stability of katA mRNA and the activity of KatA and consequently the oxidation resistance of D.radiodurans. We are the first one to explore the super-strong oxidative stress resistance of D.radiodurans at the level of post-transcriptional regulation, and found a new pathway that provides a new explanation for the long-term adaptability of D.radiodurans in extreme environments.

14.
Cancer Epidemiol Biomarkers Prev ; 28(12): 2106-2114, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31533939

RESUMO

BACKGROUND: In the clinical practice of ovarian cancer, the application of autophagy, an important regulator of carcinogenesis and chemoresistance, is still limited. This study aimed to establish a scoring system based on expression profiles of pivotal autophagy-related (ATG) genes in patients with stage III/IV ovarian cancer who received chemotherapy. METHODS: Data of ovarian serous cystadenocarcinoma in The Cancer Genome Atlas (TCGA-OV) were used as training dataset. Two validation datasets comprised patients in a Chinese local database and a dataset from the Gene Expression Omnibus (GEO). ATG genes significantly (P < 0.1) associated with overall survival (OS) were selected and aggregated into an ATG scoring scale, of which the abilities to predict OS and recurrence-free survival (RFS) were examined. RESULTS: Forty-three ATG genes were selected to develop the ATG score. In TCGA-OV, patients with lower ATG scores had better OS [HR = 0.41; 95% confidence interval (CI), 0.26-0.65; P < 0.001] and RFS [HR = 0.47; 95% CI, 0.27-0.82; P = 0.007]. After complete or partial remission to primary therapy, the rate of recurrence was 47.2% in the low-score group and 68.3% in the high-score group (odds ratio = 0.42; 95% CI, 0.18-0.92; P = 0.03). Such findings were verified in the two validation datasets. CONCLUSIONS: We established a novel scoring system based on pivotal ATG genes, which accurately predicts the outcomes of patients with advanced ovarian cancer after chemotherapy. IMPACT: The present ATG scoring system may provide a novel perspective and a promising tool for the development of personalized therapy in the future.

15.
Biomater Sci ; 7(11): 4738-4747, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31502601

RESUMO

Current nanomedicine suffers from a big challenge due to the fact that most of the nanocarrier systems lack the desired tumor penetration depth, thereby limiting their clinical translation. Unlike the nanomaterials with a similar size or shape, microgels display excellent softness, fluidity and deformability, as well as stimuli-responsiveness in the tumor microenvironment. Herein, we report the synthesis of temperature-responsive poly(N-vinylcaprolactam)/oligo (ethylene glycol) acrylate/glycidyl methacrylate (PVCL/OEGA/GMA) microgels with different hydrodynamic radii (100-500 nm), crosslinking densities, 2-methoxyethyl acrylate (MEA) contents and OEGA chain lengths using a precipitation polymerization method and the investigation of the microgels in terms of their tumor penetration capability using a multicellular tumor spheroid (MCTS) model. The prepared microgels were well characterized with different techniques. We show that regardless of the size, crosslinking density, MEA content and OEGA chain length, all microgels display the desired cytocompatibility in the given concentration range. In vitro cellular uptake data reveal that similar to 2-dimensional (2-D) adherent cells, microgels with a smaller size display more enhanced cellular uptake than those having a larger size in the 3-D MCTS model. Likewise, 3-D MCTS penetration results indicate that the PVCL/OEGA/GMA microgels with the smallest radius of 100 nm exhibit the deepest penetration length. We then selected the microgels with a radius of 200 nm but with different physicochemical parameters to investigate their cellular uptake and tumor penetration behavior. Our data show that microgels with varying crosslinking densities, MEA contents and OEGA chain lengths do not have any appreciable changes in terms of their cellular uptake and penetration in the 3-D MCTS model. Our study provides new insights for the design of different microgel-based systems for further cancer theranostic applications.

16.
Nat Nanotechnol ; 14(8): 730, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31384019
17.
Plant Sci ; 286: 7-16, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31300144

RESUMO

Cotton fibers are developed epidermal cells of the seed coat and contain large amounts of cellulose and minor lignin-like components. Lignin in the cell walls of cotton fibers effectively provides mechanical strength and is also presumed to restrict fiber elongation and secondary cell wall synthesis. To analyze the effect of lignin and lignin-like phenolics on fiber quality and the transcriptional regulation of lignin synthesis in cotton fibers, we characterized the function of a bHLH transcription factor, GhbHLH18, during fiber elongation stage. GhbHLH18 knock-down plants have longer and stronger fibers, and accumulate less lignin-like phenolics in mature cotton fibers than control plants. By mining public transcriptomic data for developing fibers, we discovered that GhbHLH18 is coexpressed with most lignin synthesis pathway genes. Furthermore, we showed that GhbHLH18 strongly binds to the E-box in the promoter region of GhPER8 and activates its expression. Transient over expression of GhPER8 protein in tobacco leaves significantly decreased the content of coniferyl alcohol and sinapic alcohol-the substrate respectively for G-lignin and S-lignin biosynthesis. These results suggest that GhbHLH18 is negatively associated with fiber quality by activating peroxidase-mediated lignin metabolism, thus the paper represents an alternative strategy to improve fiber quality.


Assuntos
Fibra de Algodão/análise , Gossypium/genética , Lignina/biossíntese , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Gossypium/metabolismo , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo
18.
J Cancer ; 10(10): 2261-2275, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31258730

RESUMO

Objective: Increasing evidence suggested that dysregulated small nucleolar RNAs (snoRNAs) were involved in tumor development. The roles of snoRNA 71A (SNORA71A) in the progression of non-small cell lung cancer (NSCLC) remained unclear. Methods: Dataset GSE19188 from Gene Expression Omnibus (GEO) database was downloaded to detect the expression levels of SNORA71A in NSCLC tissues. The biological significance of SNORA71A was explored by loss-of-function analysis both in vitro and in vivo. Results: SNORA71A was overexpressed in NSCLC tissues compared with normal tissues, and upregulated SNORA71A was significantly associated with worse survival of NSCLC patients. Knockdown of SNORA71A suppressed proliferation of both A549 and PC9 cells, and induced G0/G1 phase arrest. Knockdown of SNORA71A also suppressed xenograft tumor growth in mice. In addition, knockdown of SNORA71A inhibited cell invasion and migration and suppressed epithelial-mesenchymal transition. Furthermore, downregulated SNORA71A decreased the phosphorylation of MEK and ERK1/2 in the MAPK/ERK signal pathway. Conclusion: SNORA71A functions as an oncogene in NSCLC and may serve as a therapeutic target and promising prognostic biomarker of NSCLC.

19.
Int J Biol Sci ; 15(5): 999-1009, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31182920

RESUMO

With the advancement of nanotechnology, various nanocomposites have been applied in the diagnostics and treatment of cancer. We synthetized FePt nanoparticles which were assembled on the surface of graphene oxide (GO). These novel FePt/GO nanosheets simultaneously act as a chemotherapy drug and enhance radiosensitivity. In this study, transmission electron microscope, dynamic light scattering, X-ray photoelectron spectroscope and Fourier transform infrared spectroscopy were used to characterize surface morphology and chemical composition of FePt/GO nanosheets (NSs). Their cytotoxicity in various cancer and normal cells was evaluated by cell counting kit-8 assay, and their effects on radiosensitization were determined by colony formation assay. To explore the underlying mechanisms, we measured the intracellular reactive oxygen species levels and autophagy formation. Monodansylcadaverine-staining, Western Blotting and ultrastructure analysis were utilized to assess autophagy. The results demonstrated that FePt/GO NSs not only selectively suppressed the proliferation of cancer cells, but also increased their radiosensitization. Moreover, FePt/GO NSs induced autophagy, which might result in promoted sensibilization of radiotherapy. In conclusion, with good safety and efficacy, FePt/GO NSs are safe and effective to suppress proliferation, enhance radiosensitization and induce autophagy of human non-small cell lung cancer cells. They are potential for the treatment of lung cancer.

20.
Hum Mol Genet ; 28(13): 2201-2211, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31220268

RESUMO

Autism spectrum disorder (ASD) encompasses a collection of complex neuropsychiatric disorders characterized by deficits in social functioning, communication and repetitive behaviour. Building on recent studies supporting a role for developmentally moderated regulatory genomic variation in the molecular aetiology of ASD, we quantified genome-wide patterns of DNA methylation in 223 post-mortem tissues samples isolated from three brain regions [prefrontal cortex, temporal cortex and cerebellum (CB)] dissected from 43 ASD patients and 38 non-psychiatric control donors. We identified widespread differences in DNA methylation associated with idiopathic ASD (iASD), with consistent signals in both cortical regions that were distinct to those observed in the CB. Individuals carrying a duplication on chromosome 15q (dup15q), representing a genetically defined subtype of ASD, were characterized by striking differences in DNA methylationacross a discrete domain spanning an imprinted gene cluster within the duplicated region. In addition to the dramatic cis-effects on DNA methylation observed in dup15q carriers, we identified convergent methylomic signatures associated with both iASD and dup15q, reflecting the findings from previous studies of gene expression and H3K27ac. Cortical co-methylation network analysis identified a number of co-methylated modules significantly associated with ASD that are enriched for genomic regions annotated to genes involved in the immune system, synaptic signalling and neuronal regulation. Our study represents the first systematic analysis of DNA methylation associated with ASD across multiple brain regions, providing novel evidence for convergent molecular signatures associated with both idiopathic and syndromic autism.

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