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1.
Sci China Life Sci ; 2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32048161

RESUMO

Inflammatory leukocytes infiltration is orchestrated by mechanisms involving chemokines, selectins, addressins and other adhesion molecules derived from endothelial cells (ECs), but how they respond to inflammatory cues and coordinate leukocyte transmigration remain elusive. In this study, using hepatic ischemia/reperfusion injury (HIRI) as a model, we identified that endothelial Notch activation was rapidly and dynamically induced in liver sinusoidal endothelial cells (LSECs) in acute inflammation. In mice with EC-specific Notch activation (NICeCA), HIRI induced exacerbated liver damage. Consistently, endothelial Notch activation enhanced neutrophil infiltration and tumor necrosis factor (TNF)-α expression in HIRI. Transcriptome analysis and further qRT-PCR as well as immunofluorescence indicated that endomucin (EMCN), a negative regulator of leukocyte adhesion, was downregulated in LSECs from NICeCA mice. EMCN was downregulated during HIRI in wild-type mice and in vitro cultured ECs insulted by hypoxia/re-oxygenation injury. Notch activation in ECs led to increased neutrophil adhesion and transendothelial migration, which was abrogated by EMCN overexpression in vitro. In mice deficient of RBPj, the integrative transcription factor of canonical Notch signaling, although overwhelming sinusoidal malformation aggravated HIRI, the expression of EMCN was upregulated; and pharmaceutical Notch blockade in vitro also upregulated EMCN and inhibited transendothelial migration of neutrophils. The Notch activation-exaggerated HIRI was compromised by blocking LFA-1, which mediated leukocyte adherence by associating with EMCN. Therefore, endothelial Notch signaling controls neutrophil transmigration via EMCN to modulate acute inflammation in HIRI.

2.
Mol Genet Genomic Med ; 8(2): e1079, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31867841

RESUMO

BACKGROUND: One of the major challenges in managing invasive breast cancer (BC) is the lack of reliable biomarkers to track response. Circulating tumor DNA (ctDNA) from liquid biopsy, as a candidate biomarker, provides a valuable assessment of BC patients. In this retrospective study, we evaluated the utility of ctDNA to reflect the efficacy of treatment and to monitor resistance mechanisms. METHODS: Targeted next-generation sequencing (NGS) of 416 cancer-relevant genes was performed on 41 plasma biopsy samples of 19 HER2+ and 12 HER2- BC patients. Longitudinal ctDNA samples were analyzed in three BC patients over the treatment course for detecting acquired mutations. RESULTS: In HER2+ BC patients, ERBB2 somatic copy numbers in ctDNA samples were significantly higher in patients progressed on HER2-targeted therapy than those who were still responding to the treatment. Recurrent acquired mutations were detected in genes including ERBB2, TP53, EGFR, NF1, and SETD2, which may contribute to trastuzumab resistance. In longitudinal analyses, the observed mutation allele frequencies were tracked closely in concordance with treatment responses. A novel ERBB2 p.(Leu869Arg) mutation was acquired in one patient upon resistant to trastuzumab therapy, which was further validated as an oncogenic mutation in vitro and contributed to resistance. In HER2- BC patients with chemotherapy resistance, genetic alterations on TP53, PIK3CA, and DNA damage repair genes were frequently observed. CONCLUSIONS: In summary, ctDNA monitoring, particularly longitudinal analyses, provides valuable insights into the assessment of targeted therapy efficacy and gene alterations underlying trastuzumab resistance and chemotherapy resistance in HER2+ and HER2- BC patients, respectively.

3.
Cogn Affect Behav Neurosci ; 19(2): 327-337, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30488229

RESUMO

We proposed that self-affirmation can endow people with more cognitive resource to cope with uncertainty. We tested this possibility with an event-related potential (ERP) study by examining how self-affirmation influences ambiguous feedback processing in a simple gambling task, which was used to investigate risk decision-making. We assigned 48 participants randomly to the affirmation and non-affirmation (i.e., control) groups. All participants accepted the manipulation first and then completed the gambling task with an electroencephalogram (EEG) recording, in which participants might receive a positive (winning), negative (losing), or ambiguous (unknown valence) outcome after they made a choice. We considered both the feedback-related negativity (FRN) and P3 components elicited by the outcome feedback, which reflected the amount of cognitive resources being invested in the early and late stages of the outcome feedback processing, respectively. ERP results showed that ambiguous feedback elicited a larger FRN among affirmed participants than unaffirmed participants but exerted no influence on the P3. This finding suggests that self-affirmation may help coping with uncertainty by enhancing the early processing of uncertainty.

4.
J Cell Physiol ; 234(6): 9525-9534, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30370660

RESUMO

Sprouting angiogenesis is a major form of neovascularization of tissues suffering from hypoxia and other related stress. Endothelial cells (ECs) undergo proliferation, differentiation, programmed death, and migration during angiogenic sprouting, but the underlying molecular mechanisms regulating ECs in angiogenesis have been incompletely elucidated. Here we report that the transmembrane protein 215 (TMEM215) is involved in angiogenesis by regulating EC survival. The murine TMEM215 gene, which possesses two transcriptional starting sites as determined by 5'-rapid amplification of complementary DNA (cDNA) ends (RACE), encodes a two-pass TMEM. The TMEM215 transcripts were detected in ECs in addition to other tissues by quantitative reverse transcription-polymerase chain reaction. Immunofluorescence showed that TMEM215 was expressed in the vasculature in retina, liver, and tumor, and colocalized with EC markers. We show that knockdown of TMEM215 in ECs induced strong cell death of ECs in vitro without affecting cell proliferation and migration, suggesting that TMEM215 was required for EC survival. Downregulation of TMEM215 expression compromised lumen formation and sprouting capacities of ECs in vitro. Moreover, intravitreous injection of TMEM215 small interfering RNA resulted in delayed and abnormal development of retinal vasculature with poor perfusion. These results identified TMEM215 as a novel molecule involved in angiogenesis by regulating the survival of ECs.

5.
Psychol Rep ; 122(5): 1666-1677, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30080110

RESUMO

Previous studies have pondered the relevance of social networking sites (SNSs) to psychological well-being, but few have taken online affective experience into consideration. To extend previous research on the relationship between SNSs and psychological well-being, we opted to target emotions experienced while visiting SNSs as a means to predict off-line well-being. In our two studies, we surveyed affective experience on SNSs, overall life satisfaction, and general emotional well-being of young adults who access SNSs regularly. The results consistently demonstrated a positive association between SNS affective experience and off-line well-being. This finding held with SNS activities (Studies 1 and 2) and relevant personality traits (i.e., the Big Five factors, self-esteem; Study 2) considered in simultaneity. Our research highlights the important role of affective experience on SNSs in predicting off-line well-being as well as helps clarify the relationship between SNSs and well-being.

6.
Front Psychol ; 9: 1739, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30283384

RESUMO

Previous evidence suggests that narcissistic people tend to visit social networking sites (SNS) frequently, but the emotions accompanying their engagement on such sites has not been a significant subject of study. Therefore, we examined the relationship between narcissism and the affective experience on SNS in two different samples. To do so, we not only examined narcissism as a whole but also distinguished between adaptive and maladaptive narcissism. Results of the two studies consistently showed that: (1) narcissism as a whole was not correlated with the SNS affective experience; (2) maladaptive narcissism was predictive of a worse affective experience on SNS; and (3) partly due to a positive correlation with self-esteem, adaptive narcissism was associated with a better SNS affective experience. In addition, these findings held with SNS activities considered in simultaneity. The present research extends our understanding of the relationship between narcissism and social networking as well as that between emotion and social networking.

7.
Soc Cogn Affect Neurosci ; 13(8): 889-897, 2018 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-30016494

RESUMO

Narcissists are prone to risky decision-making, but why? This study tested-via behavioral and event-related potential (ERP) measures-two accounts: deficiencies in error monitoring and deficiencies in action updating. High and low narcissists were engaged in a monetary gambling task by choosing between a high-risk and a low-risk option while the electroencephalogram (EEG) was being recorded. Two ERP components relevant to outcome evaluation-feedback-related negativity (FRN) and P3-were analyzed, with the FRN serving as an index of error monitoring and the P3 as an index of action updating. Generally, high and low narcissists differed in the high-risk condition but not in the low-risk condition. At the behavioral level, high (vs low) narcissists made riskier decisions following high-risk decision outcomes, which was in line with past findings; at the neurophysiological level, while no FRN difference emerged between high and low narcissists, the outcome valence effect (positive vs negative) on the P3 was stronger among low narcissists than high narcissists following high-risk decision outcomes. One possible interpretation of the results is that narcissism is associated with reduced action updating. The findings contribute to the understanding of narcissistic decision-making and self-regulation.


Assuntos
Tomada de Decisões/fisiologia , Narcisismo , Assunção de Riscos , Eletroencefalografia , Eletroculografia , Potenciais Evocados , Retroalimentação Psicológica/fisiologia , Feminino , Jogo de Azar/psicologia , Humanos , Masculino , Adulto Jovem
8.
Angiogenesis ; 21(3): 635-652, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29675549

RESUMO

Ocular neovascularization is a comprehensive process involved in retinal vascular development and several blinding diseases such as age-related macular degeneration and retinopathy of prematurity, with vascular endothelial growth factor (VEGF) regarded as the master regulator. However, the qualified effect of anti-VEGF therapy reveals that the underlying mechanisms are still not clearly identified. To initialize angiogenesis, endothelial cells undergo a phenotype switching to generate highly migratory and invasive cells. This process shares certain similar characters observed in endothelial-mesenchymal transition (EndMT). Here, we found that SNAI1, an EndMT transcription factor, was expressed by endothelial cells in both physiological and pathological ocular neovascularization. SNAI1 overexpression triggered cell morphological change and enhanced cell motility, while loss of SNAI1 attenuated migration, invasion and sprouting. RNA sequence analysis further revealed that SNAI1 knockdown decreased the expression of genes related to cytoskeleton rearrangement and ECM remodeling. Moreover, intravitreal injection of small interfering RNA of SNAI1 suppressed new vessel formation in developing retina as well as mice model of choroidal neovascularization and oxygen-induced retinopathy. Therefore, we propose that the EndMT transcription factor SNAI1 promotes the early phase of ocular neovascularization and may provide a potential therapeutic target.


Assuntos
Neovascularização Patológica/fisiopatologia , Retina/fisiopatologia , Neovascularização Retiniana/fisiopatologia , Vasos Retinianos/fisiopatologia , Fatores de Transcrição da Família Snail/metabolismo , Animais , Movimento Celular/genética , Citoesqueleto/genética , Citoesqueleto/metabolismo , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Masculino , Camundongos , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Retina/metabolismo , Retina/patologia , Neovascularização Retiniana/genética , Neovascularização Retiniana/patologia , Vasos Retinianos/metabolismo , Vasos Retinianos/patologia , Análise de Sequência de RNA , Fatores de Transcrição da Família Snail/genética
9.
Hepatology ; 68(2): 677-690, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29420858

RESUMO

Liver sinusoidal endothelial cells (LSECs) critically regulate liver homeostasis and diseases through angiocrine factors. Notch is critical in endothelial cells (ECs). In the current study, Notch signaling was activated by inducible EC-specific expression of the Notch intracellular domain (NIC). We found that endothelial Notch activation damaged liver homeostasis. Notch activation resulted in decreased fenestration and increased basement membrane, and a gene expression profile with decreased LSEC-associated genes and increased continuous EC-associated genes, suggesting LSEC dedifferentiation. Consistently, endothelial Notch activation enhanced hepatic fibrosis (HF) induced by CCl4 . Notch activation attenuated endothelial nitric oxide synthase (eNOS)/soluble guanylate cyclase (sGC) signaling, and activation of sGC by 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) reversed the dedifferentiation phenotype. In addition, Notch activation subverted the hepatocyte-supporting angiocrine profile of LSECs by down-regulating critical hepatocyte mitogens, including Wnt2a, Wnt9b, and hepatocyte growth factor (HGF). This led to compromised hepatocyte proliferation under both quiescent and regenerating conditions. Whereas expression of Wnt2a and Wnt9b was dependent on eNOS-sGC signaling, HGF expression was not rescued by the sGC activator, suggesting heterogeneous mechanisms of LSECs to maintain hepatocyte homeostasis. CONCLUSION: Endothelial Notch activation results in LSEC dedifferentiation and accelerated liver fibrogenesis through eNOS-sGC signaling, and alters the angiocrine profile of LSECs to compromise hepatocyte proliferation and liver regeneration (LR). (Hepatology 2018).


Assuntos
Células Endoteliais/metabolismo , Hepatócitos/metabolismo , Cirrose Hepática/metabolismo , Regeneração Hepática/genética , Receptores Notch/metabolismo , Animais , Western Blotting , Técnicas de Cultura de Células , Proliferação de Células , Células Endoteliais/patologia , Ensaio de Imunoadsorção Enzimática , Perfilação da Expressão Gênica , Fígado/metabolismo , Fígado/patologia , Regeneração Hepática/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/genética
10.
Oncol Rep ; 38(4): 2426-2434, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28765941

RESUMO

B7-H3, a co-stimulatory molecule, has been found expressed in ovarian cancer, but its role and mechanism is not clear. In this study, we further verified the expression of B7-H3 in ovarian carcinoma and normal epithelial ovarian tissues. Three ovarian cancer cell lines, A2780, SKOV3 and HO8910 were selected to explore the effects of B7-H3 on proliferation, apoptosis, migration and invasion. We found that B7-H3 was mainly located in the cytoplasm of ovarian cancer cells as determined by immunofluorescence staining. The ability of cell invasion, migration, proliferation decreased after silencing B7-H3 whereas the apoptosis increased, which was related to the upregulation of Bax, caspase-8, cleaved caspase-8 and the downregulation of Bcl-2, Bcl-xl, matrix metalloproteinase-2 (MMP2) by western blotting. In addition, B7-H3 enhanced the H08910 cell capacities in invasion, migration and proliferation. Expression of the phosphorylation signal transducer and activator of transcription 3 (pStat3) molecules and their upstream molecules phosphorylation Janus kinase 2 (pJak2) were significantly increased. In order to investigate whether B7-H3 plays a role in this pathway, we treated the overexpressed HO8910 cells with AG490 (inhibitors of Jak2). Our findings revealed that B7-H3 affect ovarian cancer progression through the Jak2/Stat3 pathway, indicating that B7-H3 has the potential to be a useful prognostic marker.


Assuntos
Antígenos B7/genética , Biomarcadores Tumorais/genética , Janus Quinase 2/genética , Neoplasias Ovarianas/genética , Fator de Transcrição STAT3/genética , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Janus Quinase 2/antagonistas & inibidores , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias Ovarianas/patologia , Transdução de Sinais/genética , Tirfostinas/administração & dosagem
11.
Sci Rep ; 7(1): 9571, 2017 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-28851887

RESUMO

To improve the performance of inverted polymer solar cells based on a ternary blend of polymerthieno [3,4-b] thiophene/benzodithiophene (PTB7), [6,6]-phenyl C71-butyric acid methyl ester (PC71BM) and indene-C60-bisadduct (ICBA), a two-layer structure of zinc oxide (ZnO) and Al-doped zinc oxide (AZO) nanoperticles is used to improve electron extraction. Comparing to ZnO, AZO has lower work function and thus provides larger built-in potential across the organic heterojunction, resulting in more efficient photo-current extraction and larger open circuit voltages. Optimum devices with ZnO/AZO nanoparticles show enhancement of both short circuit current and open circuit voltage, leading to a power conversion efficiency (PCE) of 8.85%. The argument of energy level buffering and surface morphology is discussed in the paper. Finally, using a trilayer electron transporting unit of ZnO/AZO/PFN, the interface dipole between the organic active layer and AZO is introduced. The PCE is further enhanced to 9.17%.

12.
Q J Exp Psychol (Hove) ; 70(6): 1023-1032, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26444132

RESUMO

Western participants endorse a higher number of positive traits as self-descriptive, but endorse a lower number of negative traits as self-descriptive. They also respond quicker to categorize positive traits as self-descriptive, but respond slower to categorize negative traits as self-descriptive. Is this self-positivity bias qualified by the cultural value of modesty? We induced modesty (vs. punctuality) and assessed self-descriptiveness judgments and response times among Chinese participants. We replicated the self-positivity bias in regards to both self-descriptiveness judgments and response times. In the case of self-descriptiveness judgments, however, the bias was partially qualified by modesty. Relative to control participants, those in the modesty condition endorsed fewer positive traits as self-descriptive and manifested a tendency toward endorsing more negative traits as self-descriptive. In the case of response times, the self-positivity bias was unqualified by modesty. Within both conditions, participants were quicker to categorize positive traits as self-descriptive and were slower to categorize negative traits as self-descriptive. The results speak to the relation between the self-positivity bias and the self-reference effect and illustrate the malleability of self-processing.


Assuntos
Cultura , Julgamento , Autoimagem , Adolescente , Adulto , Análise de Variância , Viés , Feminino , Humanos , Masculino , Tempo de Reação , Adulto Jovem
13.
Biochem Biophys Res Commun ; 483(1): 488-494, 2017 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-28007595

RESUMO

Although it has been suggested that Dll3, one of the Notch ligands, promotes the proliferation and inhibits the apoptosis of cancer cells, the role of Dll3 in cancers remains unclear. In this study, we found that in the murine Lewis lung carcinoma (LLC) cells, the level of Dll3 mRNA changed upon tumor microenvironment (TME) stimulation, namely, decreased under hypoxia or stimulated with tumor necrosis factor (TNF)-α. Dll3 was also expressed at higher level in human lung carcinoma tissues than in the para-carcinoma tissues. Overexpression of Dll3 in LLC cells promoted cell proliferation and reduced apoptosis in vitro, and enhanced tumor growth when inoculated in vivo in mice. The Dll3-mediated proliferation could be due to increased Akt phosphorylation in LLC cells, because an Akt inhibitor counteracted Dll3-induced proliferation. Moreover, Dll3 overexpression promoted PI3K/Akt signaling through inhibiting Notch signaling.


Assuntos
Carcinoma Pulmonar de Lewis/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Membrana/metabolismo , Receptores Notch/metabolismo , Animais , Carcinoma Pulmonar de Lewis/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Hipóxia Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pulmonares/patologia , Proteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Células Tumorais Cultivadas , Microambiente Tumoral/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
14.
J Am Heart Assoc ; 5(2)2016 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-26857067

RESUMO

BACKGROUND: Endothelial cells (ECs) form blood vessels through angiogenesis that is regulated by coordination of vascular endothelial growth factor (VEGF), Notch, transforming growth factor ß, and other signals, but the detailed molecular mechanisms remain unclear. METHODS AND RESULTS: Small RNA sequencing initially identified miR-342-5p as a novel downstream molecule of Notch signaling in ECs. Reporter assay, quantitative reverse transcription polymerase chain reaction and Western blot analysis indicated that miR-342-5p targeted endoglin and modulated transforming growth factor ß signaling by repressing SMAD1/5 phosphorylation in ECs. Transfection of miR-342-5p inhibited EC proliferation and lumen formation and reduced angiogenesis in vitro and in vivo, as assayed by using a fibrin beads-based sprouting assay, mouse aortic ring culture, and intravitreal injection of miR-342-5p agomir in P3 pups. Moreover, miR-342-5p promoted the migration of ECs, accompanied by reduced endothelial markers and increased mesenchymal markers, indicative of increased endothelial-mesenchymal transition. Transfection of endoglin at least partially reversed endothelial-mesenchymal transition induced by miR-342-5p. The expression of miR-342-5p was upregulated by transforming growth factor ß, and inhibition of miR-342-5p attenuated the inhibitory effects of transforming growth factor ß on lumen formation and sprouting by ECs. In addition, VEGF repressed miR-342-5p expression, and transfection of miR-342-5p repressed VEGFR2 and VEGFR3 expression and VEGF-triggered Akt phosphorylation in ECs. miR-342-5p repressed angiogenesis in a laser-induced choroidal neovascularization model in mice, highlighting its clinical potential. CONCLUSIONS: miR-342-5p acts as a multifunctional angiogenic repressor mediating the effects and interaction among angiogenic pathways.


Assuntos
Neovascularização de Coroide/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , MicroRNAs/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Receptor Notch1/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Regiões 3' não Traduzidas , Animais , Sítios de Ligação , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neovascularização de Coroide/genética , Neovascularização de Coroide/patologia , Neovascularização de Coroide/prevenção & controle , Modelos Animais de Doenças , Endoglina/genética , Endoglina/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Células HeLa , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , MicroRNAs/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt , Receptor Notch1/genética , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Transfecção , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
15.
ACS Appl Mater Interfaces ; 8(5): 3301-7, 2016 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-26754052

RESUMO

A highly efficient inverted polymer solar cell (PSC) has been successfully demonstrated by using a ZnO nanoparticle (NP) and poly[(9,9-bis(3'-(N,N-dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9-dioctyfluorene)] (PFN) bilayer structure as an effective electron collecting layer. This ZnO/PFN bilayer structure is designed to combine the advantages of both ZnO and PFN, based on the performance comparison of ZnO-only, PFN-only, and ZnO/PFN bilayer devices in our work. ZnO NPs can serve as an efficient electron transport and buffer layer for reduced series resistance, while the PFN interlayer can improve the energy level alignment of devices through the formation of an interfacial dipole. With the enhanced electron extraction induced by the ZnO/PFN bilayer structure and PTB7:ICBA:PC71BM ternary system, the corresponding inverted PSC device shows a high PCE of 9.3%, which is more than a 15% improvement compared to the ZnO- or PFN-only devices.

16.
Oncotarget ; 6(42): 44373-87, 2015 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-26517242

RESUMO

DNA methylation is clinically relevant to important tumorigenic mechanisms. This study evaluated the methylation status of candidate genes in cervical neoplasia and determined their diagnostic performance in clinical practice. Cervical cancer and normal cervix tissue was used to select the top 5 discriminating loci among 27 loci in 4 genes (CCNA1, CADM1, DAPK1, JAM3), and one locus of JAM3 (region M4) was identified and confirmed with 267 and 224 cervical scrapings from 2 independent colposcopy referral studies. For patients with atypical squamous cells of unknown significance and those with low-grade squamous intraepithelial lesion, with JAM3-M4 compared to a triage marker of hrHPV testing, the specificity for cervical intraepithelial neoplasia 3 CIN3 and cancer cases (CIN3+) / no neoplasia and CIN1 (CIN1-) was significantly increased, from 21.88 to 81.82 and 15.38 to 85.18, respectively. The corresponding positive predictive value (PPV) was increased from 26.47 to 57.14 and 18.52 to 63.64, respectively. For hrHPV-positive patients, compared to a triage marker of cytology testing, JAM3-M4 showed increased specificity and PPV, from 30.67 to 87.65 and 38.82 to 82.14, respectively. We assessed whether JAM3-M4 could distinguish productive from transforming CIN2; the coincidence rate of JAM3-M4 and P16 was as high as 60.5%.


Assuntos
Células Escamosas Atípicas do Colo do Útero , Biomarcadores Tumorais/genética , Moléculas de Adesão Celular/genética , Neoplasia Intraepitelial Cervical/genética , Metilação de DNA , Infecções por Papillomavirus/genética , Lesões Pré-Cancerosas/genética , Lesões Intraepiteliais Escamosas Cervicais/genética , Neoplasias do Colo do Útero/genética , Adulto , Área Sob a Curva , Células Escamosas Atípicas do Colo do Útero/química , Células Escamosas Atípicas do Colo do Útero/patologia , Células Escamosas Atípicas do Colo do Útero/virologia , Biomarcadores Tumorais/análise , Neoplasia Intraepitelial Cervical/química , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Lesões Pré-Cancerosas/química , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/virologia , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Lesões Intraepiteliais Escamosas Cervicais/metabolismo , Lesões Intraepiteliais Escamosas Cervicais/patologia , Lesões Intraepiteliais Escamosas Cervicais/virologia , Neoplasias do Colo do Útero/química , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal
17.
PLoS One ; 10(4): e0124924, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25923701

RESUMO

Recent advances in the synthesis of multi-functional nanoparticles have opened up tremendous opportunities for the targeted delivery of genes of interest. Cationic solid lipid nanoparticles (SLN) can efficiently bind nucleic acid molecules and transfect genes in vitro. Few reports have combined SLN with therapy using decoy oligodeoxynucleotides (ODN). In the present study, we prepared SLN to encapsulate STAT3 decoy ODN; then, the properties and in vitro behavior of SLN-STAT3 decoy ODN complexes were investigated. SLN-STAT3 decoy ODN complexes were efficiently taken up by human ovarian cancer cells and significantly suppressed cell growth. Blockage of the STAT3 pathway by SLN-STAT3 decoy ODN complexes resulted in an evident induction of cell death, including apoptotic and autophagic death. The mechanism involved the increased expression of cleaved caspase 3, Bax, Beclin-1 and LC3-II and reduced expression of Bcl-2, pro-caspase 3, Survivin, p-Akt and p-mTOR. In addition, SLN-STAT3 decoy ODN complexes inhibited cell invasion by up-regulating E-cadherin expression and down-regulating Snail and MMP-9 expression. These findings confirmed that SLN as STAT3 decoy ODN carriers can induce cell death and inhibit invasion of ovarian cancer cells. We propose that SLN represent a potential approach for targeted gene delivery in cancer therapy.


Assuntos
Apoptose , Nanopartículas/química , Oligonucleotídeos Antissenso/metabolismo , Fator de Transcrição STAT3/metabolismo , Autofagia , Caderinas/metabolismo , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Feminino , Técnicas de Transferência de Genes , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Microscopia Eletrônica de Transmissão , Oligonucleotídeos Antissenso/química , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/genética , Fatores de Transcrição da Família Snail , Fatores de Transcrição/metabolismo , Regulação para Cima
18.
Sci China Life Sci ; 58(5): 425-31, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25833803

RESUMO

Due to its essential roles in angiogenesis, Notch pathway has emerged as an attractive target for the treatment of pathologic angiogenesis. Although both activation and blockage of Notch signal can impede angiogenesis, activation of Notch signal may be more promising because it was shown that long-term Notch signal blockage resulted in vessel neoplasm. However, an in vivo deliverable Notch ligand with highly efficient Notch-activating capacity has not been developed. Among all the Notch ligands, Delta-like4 (Dll4) is specifically involved in angiogenesis. In this study, we generated a novel soluble Notch ligand hD4R, which consists of the Delta-Serrate-Lag-2 fragment of human Dll4 and an arginine-glycine-aspartate (RGD) motif targeting endothelial cells (ECs). We demonstrated that hD4R could bind to ECs through its RGD motif and effectively triggered Notch signaling in ECs. Further, we confirmed that hD4R could suppress angiogenesis in vitro as manifested by network formation assay and sprouting assay. More importantly, hD4R efficiently repressed neonatal retinal angiogenesis and laser-induced choroidal neovascularization (CNV) as well in vivo. In conclusion, we have developed an in vivo deliverable Notch ligand hD4R, which suppresses angiogenesis both in vitro and in vivo, thus providing a new approach to tackle excessive angiogenesis relevant disease such as CNV.


Assuntos
Neovascularização de Coroide/fisiopatologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Neovascularização Retiniana/fisiopatologia , Animais , Neovascularização de Coroide/prevenção & controle , Células Endoteliais/fisiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Técnicas In Vitro , Peptídeos e Proteínas de Sinalização Intercelular/química , Peptídeos e Proteínas de Sinalização Intercelular/genética , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica/fisiologia , Oligopeptídeos/química , Oligopeptídeos/genética , Oligopeptídeos/fisiologia , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/fisiologia , Receptores Notch/fisiologia , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Neovascularização Retiniana/prevenção & controle , Transdução de Sinais , Solubilidade
19.
Microbiol Immunol ; 59(4): 219-30, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25689106

RESUMO

A full-length cDNA of a sigma-like glutathione S-transferase (GST) was identified from Hyriopsis cumingii (HcGSTS). The deduced amino acid sequence of HcGSTS was found to comprise 203 amino acid residues and to contain the distinct highly conserved glutathione binding site of N-terminal and the relatively diverse substrate binding site of C-terminal. Alignment analysis and phylogenetic relationship suggested that the HcGSTS is a sigma-class GST. The mRNA of HcGSTS was constitutively expressed in all tested tissues, the strongest expression being in the hepatopancreas. The mRNA expression of HcGSTS was significantly up-regulated (P < 0.05) in all assessed tissues after stimulation of the mussels with peptidoglycan (PGN) and LPS, the only exception being when the gills were challenged with PGN. The expression of HcGSTS mRNA in kidney and foot was also significantly up-regulated (P < 0.05) by microcystin-LR. Recombinant HcGSTS exhibited high activity towards the substrate 1-chloro-2,4-dinitrobenzene. The optimal pH was 8.0 and temperature 35 °C.


Assuntos
Bivalves/enzimologia , Clonagem Molecular , Glutationa Transferase/química , Glutationa Transferase/genética , Sequência de Aminoácidos , Animais , Bivalves/química , Bivalves/classificação , Bivalves/genética , Estabilidade Enzimática , Glutationa Transferase/metabolismo , Concentração de Íons de Hidrogênio , Dados de Sequência Molecular , Filogenia , Alinhamento de Sequência
20.
Genet Mol Biol ; 37(3): 508-17, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25249773

RESUMO

Peptidoglycan recognition proteins (PGRPs) are innate immune molecules that have been structurally conserved throughout evolution in invertebrates and vertebrates. In this study, peptidoglycan recognition protein HcPGRP1 and its isoform HcPGRP1a were identified in the freshwater mussel Hyriopsis cumingii. The full-length cDNAs of HcPGRP1 (973 bp) and HcPGRP1a (537 bp) encoded polypeptides with 218 and 151 amino acids, respectively. Sequence analysis showed that HcPGRP1 had one C-terminal PGRP domain that was conserved throughout evolution. Phylogenetic analysis showed that HcPGRP1 clustered closely with EsPGRP4 of Euprymna scolopes. Real-time PCR showed that the mRNA transcripts of HcPGRP1 and HcPGRP1a were constitutively expressed in various tissues, with the highest level in hepatopancreas. Stimulation with lipopolysaccharide (LPS) and peptidoglycan (PGN) significantly up-regulated HcPGRP1 mRNA expression in hepatopancreas and foot, but not in gill, whereas HcPGRP1a expression was significantly up-regulated in all three tissues. Our results indicate that HcPGRP1 is both a constitutive and inducible protein that may be involved in immune responses (recognition and defense) against invaders.

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