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1.
Drug Des Devel Ther ; 13: 3539-3550, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31631978

RESUMO

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer which is associated with poor patient outcome and lack of targeted therapy. Our laboratory has synthesized a series of indole-2-carboxamide derivatives. Among this series, compound LG25 showed a favorable pharmacological profile against sepsis and inflammatory diseases. In the present study, we investigated the chemotherapeutic potential of LG25 against TNBC utilizing in vitro and in vivo models. Methods: Changes in cell viability, cell cycle phases and apoptosis were analyzed using MTT, clonogenic assay, FACS and Western blotting assays. The anti-cancer effects of LG25 were further determined in a xenograft mouse model. Results: Our findings reveal that LG25 reduced TNBC viability in a dose-dependent manner. Flow cytometric and Western blot analyses showed that LG25 enhances G2/M cell cycle arrest and induced cell apoptosis. In addition, LG25 treatment significantly inhibited Akt/mTOR phosphorylation and nuclear translocation of nuclear factor-κB (NF-κB). These inhibitory activities of LG25 were confirmed in mice implanted MDA-MB-231 TNBC cells. Conclusion: Our studies provide experimental evidence that indole-2-carboxamide derivative LG25 effectively targeted TNBC in preclinical models by inducing cell cycle arrest and apoptosis, through suppressing Akt/mTOR/NF-κB signaling pathway.

2.
Mol Nutr Food Res ; : e1900662, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31512815

RESUMO

SCOPE: Platelet integrin αIIbß3 is the key mediator of atherothrombosis. Supplementation of coenzyme Q10 (CoQ10), a fat-soluble molecule that exists in various foods, exerts protective cardiovascular effects. This study aims to investigate whether and how CoQ10 acts on αIIbß3 signaling and thrombosis, the major cause of cardiovascular diseases. METHODS AND RESULTS: Using a series of platelet functional assays in vitro, it is demonstrated that CoQ10 reduces human platelet aggregation, granule secretion, platelet spreading, and clot retraction. It is further demonstrated that CoQ10 inhibits platelet integrin αIIbß3 outside-in signaling. These inhibitory effects are mainly mediated by upregulating cAMP/PKA pathway, where CoQ10 stimulates the A2A adenosine receptor and decreases phosphodiesterase 3A phosphorylation. Moreover, CoQ10 attenuates murine thrombus growth and vessel occlusion in a ferric chloride (FeCl3 )-induced thrombosis model in vivo. Importantly, the randomized, double-blind, placebo-controlled clinical trial in dyslipidemic patients demonstrates that 24 weeks of CoQ10 supplementation increases platelet CoQ10 concentrations, enhances the cAMP/PKA pathway, and attenuates αIIbß3 outside-in signaling, leading to decreased platelet aggregation and granule release. CONCLUSION: Through upregulating the platelet cAMP/PKA pathway, and attenuating αIIbß3 signaling and thrombus growth, CoQ10 supplementation may play an important protective role in patients with risks of cardiovascular diseases.

3.
Pathol Res Pract ; 215(11): 152603, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31540771

RESUMO

miR-182 is a well-described oncogenic miRNA playing a crucial role in the development of many malignancies. However, the role of miR-182 in multiple myeloma (MM) remains unclear. Here, we demonstrate that adhesion of H929 and MM.1S cells to fibronectin could induce miR-182 expression and decrease PDCD4 expression. Furthermore, miR-182 was found to negatively regulate PDCD4 expression in H929 and MM.1S cells. In addition, PDCD4 down-regulation was required for cell adhesion-mediated drug resistance (CAM-DR). Intriguingly, miR-182 up-regulation could promote CAM-DR in H929 and MM.1S cells. Moreover, miR-182 up-regulation and PDCD4 down-regulation enhanced AKT phosphorylation at Ser473 in both H929 and MM.1S cells. Our data suggest that cell adhesion-mediated miR-182 up-regulation and PDCD4 down-regulation may confer drug resistance via enhancing AKT phosphorylation at Ser473.

4.
Zhongguo Zhen Jiu ; 39(9): 993-7, 2019 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-31544390

RESUMO

The questionnaire of Acupuncture-Moxibustion and Tuina Applying for First-Level Discipline was issued to 24 colleges and universities of TCM in China. The questionnaire systematically investigated the recent disciplinary development of acupuncture-moxibustion and tuina from the aspects of specialty construction, student enrollment, faculty construction, personnel training quality, teaching quality and scientific research results. As a result, from 2013 to October of 2017, the above aspects in 24 colleges and universities of TCM in China showed an increasing trend year by year. Based on this survey, this report aimed to fully reflect the disciplinary development of acupuncture-moxibustion and tuina in China, which could analyze the current situation for education departments and training units, and provide data reference and support for acupuncture and tuina discipline to become a first-class discipline.

5.
Biosens Bioelectron ; 142: 111577, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31430613

RESUMO

A novel nonsemiconductor photoelectrochemical biosensor was first constructed using the unique plasmonic AuNi nanodendrite arrays. The AuNi nanodendrite arrays were rapidly prepared by a one-step electrodeposition method using the porous anodic aluminum templates. Owing to its hierarchical structure with abundant active sites, the synergistic catalytic of Au and Ni can be better exploited. These plasmonic AuNi nanodendrite arrays display exceptional photoelectrocatalytic activities for glucose oxidation and hydrogen peroxide reduction reaction under visible light illumination. Specifically, the detection sensitivity for glucose (3.7277 mA mM-1 cm-2) under illumination is about 3.3 folds improvement than in the dark (1.1287 mA mM-1 cm-2), together with high accuracy and low detection limit of 3 µM. The markedly enhanced performance of AuNi nanodendrite arrays can be attributed to its hierarchical structure with abundant active sites and plasmonic effect of Au with strong absorption band in visible region. Such a newly developed method via the facile and low-cost route is of great significance in designing the plasmon-aided photoelectrochemical biosensors.

6.
Stress Health ; 35(4): 491-502, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31276289

RESUMO

Drawing upon the spillover-crossover model, this study examined the extent to which one's work time demands spilled over to the family domain and crossed over to his or her spouse, utilizing data of 365 dual-earner couples from the 500 Family Study. The results of the distinguishable actor-partner interdependence model indicated that there was gender symmetry in the spillover processes such that the effects of work hours were identical between men and women. Further, although there was more bidirectional crossover between partners within couples, we observed some unidirectional crossover from husbands to wives. Specifically, husbands only increased their contribution to domestic work in response to wives' work fatigue, whereas wives increased their contribution to domestic work in response to husbands' work fatigue and high workloads. Finally, husbands' housework hours negatively related to wives' marital satisfaction and positively related to wives' depression, whereas wives' housework hours negatively related to husbands' marital satisfaction and depression. These findings have practical implications for improving the work-family balance, health, and well-being of dual-earner couples.

7.
Phys Chem Chem Phys ; 21(31): 17087-17095, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31338491

RESUMO

The recent studies of magno-assisted tunnelling in ferromagnetic van der Waals heterostructures formed by graphene and ultrathin CrBr3 films (D. Ghazaryan et al., Nat. Electron., 2018, 1, 344) offer broader opportunities for exploration of novel quantum phenomena, especially for realizing the graphene-based quantum anomalous Hall effect (QAHE). Based on first-principles approaches, we reveal that three types of graphene/CrBr3 (Gr/CrBr3) heterostructures exhibit metallic band behavior due to strong charge-transfer at the interfaces of these heterosystems. Remarkably, the pressure-induced QAHE can be achieved in Gr/CrBr3 and CrBr3/Gr/CrBr3 systems. Further low energy k·p model analyses show that the nontrivial topological properties are mainly attributed to the Rashba spin-orbit coupling (SOC), but not to the intrinsic SOC of graphene. Moreover, a multichannel device prototype is proposed in the superlattices composed of Gr/CrBr3 and normal insulator (such as hexagonal boron nitride) layers. Our work provides an experimentally feasible scheme for realizing the high-temperature and multichannel QAHE in graphene-based heterostructures.

8.
Nanoscale ; 11(29): 13807-13814, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31294742

RESUMO

The search for more types of band inversion-induced topological states is of great scientific and experimental interest. Here, we proposed that the band inversion between px,y and pz orbitals can produce a topological phase transition in honeycomb lattices based on tight-binding model analyses. The corresponding topological phase diagram was mapped out in the parameter space of orbital energy and spin-orbit coupling. Specifically, the quantum anomalous Hall (QAH) effect could be achieved when ferromagnetism was introduced. Moreover, our first-principles calculations demonstrated that the two systems of half-iodinated silicene (Si2I) and one-third monolayer of bismuth epitaxially grown on the Si(111)-√3 ×√3 surface are ideal candidates for realizing the QAH effect with Curie temperatures of ∼101 K and 118 K, respectively. The underlying physical mechanism of this scheme is generally applicable, offering broader opportunities for the exploration of novel topological states and high-temperature QAH effect systems.

9.
Psychiatr Danub ; 31(2): 141-147, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31291217

RESUMO

BACKGROUND: Brain-derived neurotrophic factor (BDNF) polymorphism plays an important role in neural survival and was proposed to be related to obsessive-compulsive disorder (OCD). Genetic association studies of the BDNF Val66Met polymorphism (rs6265) in OCD have produced inconsistent results. A meta-analysis of studies was conducted to compare the frequency of the BDNF Val66Met variant between cases with OCD and age-matched controls. SUBJECTS AND METHODS: Electronic databases were searched for eligible articles in English and ten studies on the association of the BDNF Val66Met polymorphism with OCD were analysed. RESULTS: A total of ten studies involving 2306 cases with OCD and 4968 healthy controls were included. Findings indicated that the BDNF Val66Met polymorphism was not associated with OCD. But there was a marginally significant effect of the BDNF Val66Met variant on OCD in different ethnicity. CONCLUSION: Findings from this meta-analytic investigation of published literature provide little support for the Val66Met variant of BDNF as a predictor of OCD. Future well-powered agnostic genome-wide association studies with more refined phenotype are needed to clarify genetic influences on OCD.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Predisposição Genética para Doença , Transtorno Obsessivo-Compulsivo/genética , Polimorfismo Genético , Humanos
10.
ACS Appl Mater Interfaces ; 11(29): 26460-26466, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31267730

RESUMO

Negative exchange bias is usually discovered in ferromagnetic (FM)/antiferromagnetic (AFM) heterostructures after a field-cooling (FC) process. Relatively, positive exchange bias (PEB) is a rarely observed phenomenon. So far, almost all of the models for PEB whether undergoing FC or zero-field-cooling (ZFC) treatment have been explained by an interaction of strong AFM coupling at the interface. In this work, by selecting a special material of SrFeO3-x as the AFM layer, coupled with FM-La0.7Sr0.3MnO3 (LSMO), we obtain a novel PEB effect of the bilayer after ZFC measurement, of which the shift directions are unfixable and dependent on the initial magnetization direction. Based on a transient magnetic field to control the remanence (Mr) direction of LSMO at room temperature and then cooling below the TN of SrFeO3-x without any magnetic field disturbance, the shift direction can be locked only toward the transient magnetic field. Combined with experimental results and first-principles calculations, we propose that the above phenomena are explained as the field-induced AFM phase of SrFeO3-x transforming into the FM phase at an FM coupling bilayer interface. Thus, our finding may provide a new approach to realize and tune the zero-field-cooling PEB with FM coupling heterostructures.

11.
J Nutr Biochem ; 70: 47-55, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31151053

RESUMO

There is a strong epidemiological link between obesity, a growing worldwide concern, and kidney disease. Emerging evidence indicates that the pathogenic basis of obesity-related kidney disease may be attributed to Toll-like receptor 4 (TLR4) of the innate immune system. We hypothesized that renal epithelial cell injury in response to oxidized low-density lipoprotein (oxLDL) requires myeloid differentiation factor 2 (MD2), a co-receptor of TLR4. Moreover, we also hypothesized that renal dysfunction is MD2-dependent in the high-fat diet (HFD) mouse model. Results indicated that the MD2 selective inhibitor (L6H21) abrogated the oxLDL-induced formation of MD2-TLR4 dimerization in the renal proximal tubular epithelial cell line NRK-52E. Further, MD2 blockade in NRK-52E cells using siRNA target sequences or L6H21 prevented oxLDL-induced cell injury as indicated by expression of profibrotic molecules, autophagic activity and apoptosis. Similarly, TLR4 knockdown in NRK-52E cells using siRNA target sequences prevented oxLDL-induced cell injury. In the HFD mouse model, MD2 knockout protected against development of kidney dysfunction and renal tissue injury, corroborating the observations observed in NRK-52E cells. Thus, the oxLDL-induced renal tubular epithelial cell profibrotic responses, autophagy and apoptosis were dependent on MD2, as were the renal dysfunction and tissue impairment in HFD mice. These are new findings indicating that the MD2-TLR4 immune signaling complex is a critical pathogenic factor in the development of kidney disease related to obesity or metabolic syndrome.

12.
Neurobiol Dis ; 130: 104486, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31150793

RESUMO

Accumulated genetic evidences indicate that the contactin associated protein-like (CNTNAP) family is implicated in autism spectrum disorders (ASD). In this study, we identified genetic mutations in the CNTNAP3 gene from Chinese Han ASD cohorts and Simons Simplex Collections. We found that CNTNAP3 interacted with synaptic adhesion proteins Neuroligin1 and Neuroligin2, as well as scaffolding proteins PSD95 and Gephyrin. Significantly, we found that CNTNAP3 played an opposite role in controlling the development of excitatory and inhibitory synapses in vitro and in vivo, in which ASD mutants exhibited loss-of-function effects. In this study, we showed that the male Cntnap3-null mice exhibited deficits in social interaction, spatial learning and prominent repetitive behaviors. These evidences elucidate the pivotal role of CNTNAP3 in synapse development and social behaviors, providing mechanistic insights into ASD.

13.
Taiwan J Obstet Gynecol ; 58(3): 380-384, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31122529

RESUMO

OBJECTIVE: Currently, there is paucity of data on the rate of vaginal deliveries and cesarean section among women in Tibet. In this study, we carried out an observational study of 7365 consecutive pregnant women in Lhasa, Tibet who gave birth at our tertiary care institution between 2012 and 2015. MATERIALS AND METHODS: In this retrospective study, we reviewed the hospital records for demographic data, obstetric history, and the number of vaginal and emergency cesarean section deliveries. The overall and annual rate of vaginal and cesarean section deliveries was calculated. Causes, indications or risks for cesarean section were also analyzed. RESULTS: During the review period, 7365 neonates were delivered at our hospital, including 1690 (23.0%) deliveries via cesarean section. The yearly rate of cesarean section progressively declined from 26.7% in 2012 to 18% in 2015 (P < 0.001). Furthermore, the annual rate of emergency cesarean section declined 53.9%between 2012 and 2015(P < 0.001). Fetal risk factors (39.9%) and maternal risk factors (40.3%) were the major causes of cesarean section in the women. Social factors as a cause of cesarean section fluctuated between 7.9% and 11.1%. CONCLUSION: This study has demonstrated a steady decline in the annual rate of cesarean section in women in Tibet between 2012 and 2015. A decrease in the rate of emergency cesarean section contributed substantially to this decline. Moreover, approximately 10% caesarian sections were performed without clear indications, highlighting the need for strengthening prenatal counseling for pregnant women in Tibet.

14.
Biomed Pharmacother ; 115: 108922, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31048190

RESUMO

Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking prognostic and effective therapeutic targets currently. In this study, we evaluated the toxic potential of schisandrin A (SchA), a bioactive phytochemical found in Schisandra chinensis in TNBC. The anti-cancer effect and underlying mechanism of SchA on MDA-MB-231 and BT-549 cells were determined in vitro and in xenograft mouse model. Our data show that SchA markedly inhibited the growth of TNBC cells via induction of cell cycle arrest and cell apoptosis. Moreover, over activation of Wnt signaling was observed in TNBC cells, which was significantly suppressed by the treatment of SchA. Also, SchA treatment activated ER stress in TNBC cells. Finally, we verified these inhibitory effects of SchA in the MDA-MB-231 xenograft mouse model. In conclusion, SchA effectively inhibited TNBC in preclinical models by inducing cell cycle arrest and apoptosis via regulating Wnt/ER stress signaling pathway. All of these data indicate that SchA could be a potential candidate for the treatment of TNBC.

15.
Spat Spatiotemporal Epidemiol ; 29: 51-57, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31128631

RESUMO

The aim of this study was to assess how children's personal exposure to fine particulate matter (PM2.5) during the school commute is influenced by mode of travel and neighborhood environment in a mid-sized Canadian city. A total of 101 commutes to and from school were tracked using a GPS, and personal exposure to PM2.5 along commute routes was assessed by spatially-referencing the monitored exposure levels with time-synchronized GPS data. Students who walked to and from school were exposed to lower PM2.5 concentrations than those in cars or riding the school bus. There was also a significant difference in mean PM2.5 concentrations by the built environment, with children who walked to school in suburban neighborhoods experiencing higher personal concentrations than children in urban neighborhoods. To reduce children's daily exposure to air pollutants, neighborhoods should be designed to maximize the number of children who are able to walk between home and school.

16.
N Engl J Med ; 380(15): 1433-1441, 2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30970188

RESUMO

We report an inborn error of metabolism caused by an expansion of a GCA-repeat tract in the 5' untranslated region of the gene encoding glutaminase (GLS) that was identified through detailed clinical and biochemical phenotyping, combined with whole-genome sequencing. The expansion was observed in three unrelated patients who presented with an early-onset delay in overall development, progressive ataxia, and elevated levels of glutamine. In addition to ataxia, one patient also showed cerebellar atrophy. The expansion was associated with a relative deficiency of GLS messenger RNA transcribed from the expanded allele, which probably resulted from repeat-mediated chromatin changes upstream of the GLS repeat. Our discovery underscores the importance of careful examination of regions of the genome that are typically excluded from or poorly captured by exome sequencing.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Ataxia/genética , Deficiências do Desenvolvimento/genética , Glutaminase/deficiência , Glutaminase/genética , Glutamina/metabolismo , Repetições de Microssatélites , Mutação , Atrofia/genética , Cerebelo/patologia , Pré-Escolar , Feminino , Genótipo , Glutamina/análise , Humanos , Masculino , Fenótipo , Reação em Cadeia da Polimerase , Sequenciamento Completo do Genoma
17.
Artigo em Inglês | MEDLINE | ID: mdl-30974818

RESUMO

Although previous research has documented a host of negative consequences of job insecurity, workplace interpersonal relationships have rarely been considered. This omission might be caused by the application of broad stress theories to the job insecurity literature without taking a nuanced perspective to understand the nature of job insecurity. To address this issue, we conceptualized job insecurity as a threat to employee social acceptance by their employer. This conceptualization, therefore, allows us to apply the multimotive model of social rejection to investigate a previously-overlooked outcome of job insecurity-workplace friendships. Specifically, we investigated the relationship between both job feature insecurity and job loss insecurity with workplace friendships. Based on stress coping theory and the fundamental differences between job feature insecurity and job loss insecurity, we further proposed that employees' tendency to engage in positive gossip buffers the negative impact of job feature insecurity on workplace friendships, whereas employees' tendency to engage in negative gossip buffers the negative impact of job loss insecurity on workplace friendships. Data collected from 286 working adults from Mturk supported our hypotheses. Our study opens the door for future research to take a more nuanced approach when examining nontraditional consequences of job insecurity.


Assuntos
Comunicação , Amigos/psicologia , Satisfação no Emprego , Local de Trabalho/psicologia , Adulto , Feminino , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade
18.
Neurosci Bull ; 35(4): 697-708, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30900143

RESUMO

Adult male mice emit highly complex ultrasonic vocalizations (USVs) in response to female conspecifics. Such USVs, thought to facilitate courtship behaviors, are routinely measured as a behavioral index in mouse models of neurodevelopmental and psychiatric disorders such as autism. While the regulation of USVs by genetic factors has been extensively characterized, the neural mechanisms that control USV production remain largely unknown. Here, we report that optogenetic activation of the medial preoptic area (mPOA) elicited the production of USVs that were acoustically similar to courtship USVs in adult mice. Moreover, mPOA vesicular GABA transporter-positive (Vgat +) neurons were more effective at driving USV production than vesicular glutamate transporter 2-positive neurons. Furthermore, ablation of mPOA Vgat+ neurons resulted in altered spectral features and syllable usage of USVs in targeted males. Together, these results demonstrate that the mPOA plays a crucial role in modulating courtship USVs and this may serve as an entry point for future dissection of the neural circuitry underlying USV production.

19.
Sci Rep ; 9(1): 2654, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30804404

RESUMO

Overexpression of correctly folded membrane proteins is a fundamental prerequisite for functional and structural studies. One of the most commonly used expression systems for the production of membrane proteins is Escherichia coli. While misfolded proteins typically aggregate and form inclusions bodies, membrane proteins that are addressed to the membrane and extractable by detergents are generally assumed to be properly folded. Accordingly, GFP fusion strategy is often used as a fluorescent proxy to monitor their expression and folding quality. Here we investigated the functionality of two different multidrug ABC transporters, the homodimer BmrA from Bacillus subtilis and the heterodimer PatA/PatB from Streptococcus pneumoniae, when produced in several E. coli strains with T7 expression system. Strikingly, while strong expression in the membrane of several strains could be achieved, we observed drastic differences in the functionality of these proteins. Moreover, we observed a general trend in which mild detergents mainly extract the population of active transporters, whereas a harsher detergent like Fos-choline 12 could solubilize transporters irrespective of their functionality. Our results suggest that the amount of T7 RNA polymerase transcripts may indirectly but notably impact the structure and activity of overexpressed membrane proteins, and advise caution when using GFP fusion strategy.

20.
Nat Commun ; 10(1): 736, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760719

RESUMO

Memristors with enormous storage capacity and superior processing efficiency are of critical importance to overcome the Moore's Law limitation and von Neumann bottleneck problems in the big data and artificial intelligence era. In particular, the integration of multifunctionalities into a single memristor promises an essential strategy of obtaining a high-performance electronic device that satisfies the nowadays increasing demands of data storage and processing. In this contribution, we report a proof-of-concept polymer memristive processing-memory unit that demonstrates programmable information storage and processing capabilities. By introducing redox active moieties of triphenylamine and ferrocene onto the pendants of fluorene skeletons, the conjugated polymer exhibits triple oxidation behavior and interesting memristive switching characteristics. Associated with the unique electrochemical and electrical behavior, the polymer device is capable of executing multilevel memory, decimal arithmetic operations of addition, subtraction, multiplication and division, as well as simple Boolean logic operations.

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