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1.
JAMA Oncol ; 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31876895

RESUMO

Importance: Immune checkpoint inhibitors of programmed cell death 1 (PD-1) and its ligand (PD-L1) have led to a paradigm shift in cancer treatment. Understanding the clinical efficacy and safety profile of these drugs is necessary for treatment strategy in clinical practice. Objective: To assess the differences between anti-PD-1 and anti-PD-L1 regarding efficacy and safety shown in randomized clinical trials across various tumor types. Data Sources: Systematic searches of PubMed, Cochrane CENTRAL, and Embase were conducted from January 1, 2000, to March 1, 2019. In addition, abstracts and presentations from all major conference proceedings were reviewed. Study Selection: All randomized clinical trials that compared anti-PD-1 and anti-PD-L1 with standard treatment in patients with cancer were selected as candidates. Retrospective studies, single-arm phase 1/2 studies, and trials comparing anti-PD-1 and anti-PD-L1 with other immunotherapies were excluded. Studies of anti-PD-1 and anti-PD-L1 therapy were screened and paired by the matching of clinical characteristics as mirror groups. Data Extraction and Synthesis: Three investigators independently extracted data from each study following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline. Trial names, first author, year of publication, study design, National Clinical Trial identifier number, blinding status, study phase, pathologic characteristics, number of patients, patients' age and sex distribution, Eastern Cooperative Oncology Group Performance Status, lines of treatment, study drugs, biomarker status, follow-up time, incidence of adverse events, and hazard ratios (HRs) with 95% CIs for overall survival and progression-free survival were extracted. A random-effects model was applied for data analysis. Main Outcomes and Measures: Differences in OS between anti-PD-1 and anti-PD-L1 across different cancer types were assessed. An effect size was derived from each mirror group and then pooled across all groups using a random-effects model. Results: Nineteen randomized clinical trials involving 11 379 patients were included in the meta-analysis. Overall, anti-PD-1 exhibited superior overall survival (HR, 0.75; 95% CI, 0.65-0.86; P < .001) and progression-free survival (HR, 0.73; 95% CI, 0.56-0.96; P = .02) compared with anti-PD-L1. No significant difference was observed in their safety profiles. Sensitivity analysis presented consistency in the overall estimates across these analyses. Consistent results were observed through frequentist and bayesian approaches with the same studies. Conclusions and Relevance: Comprehensive analysis suggests that anti-PD-1 exhibited favorable survival outcomes and a safety profile comparable to that of anti-PD-L1, which may provide a useful guide for clinicians.

2.
Colloids Surf B Biointerfaces ; 174: 384-392, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30476792

RESUMO

Integrating the optical properties of near-infrared fluorescent carbon dots into liposomes may construct a multifunctional nano-system with the potential as a drug carrier, tracer and efficacy intensifier of the anticancer agent. In this study, the liposomes loaded with hydrophilic near-infrared carbon dots as a nano-carrier and tracer of lipophilic anticancer agent cinobufagin were developed. Prepared liposomes were characterized by particle size, morphology and entrapment efficiency. The drug release behavior, the tracer function, the anticancer effect and the side effect were investigated in vitro and in vivo. It was observed that the photoluminescence emission of carbon dots could be strongly enhanced up to 5 times by nano-liposomes. Due to this property, the bio-imaging of CDs + CB liposomes in vitro and in vivo could be clearly obtained. Our results also showed that the CDs + CB liposomes could be uptaken by cells (the lysosomes targeted) and delivered to the tumor site, and undoubtedly, the CDs + CB liposomes demonstrated sustained drug release, enhanced anticancer efficacy and low side effects in vivo. With the assistance of imaging function of CDs, the CDs + CB liposomes can easily display the distribution of drugs, which is very helpful for drug development and may open a novel avenue for drug delivery.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Bufanolídeos/farmacologia , Carbono/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Lipossomos/administração & dosagem , Pontos Quânticos/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose , Neoplasias da Mama/patologia , Bufanolídeos/química , Proliferação de Células , Feminino , Fluorescência , Humanos , Lipossomos/química , Camundongos , Espectroscopia de Luz Próxima ao Infravermelho , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Chemistry ; 24(59): 15806-15811, 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30187596

RESUMO

During the past decade, increasing attention has been paid to fluorescent carbon dots (CDs) due to their unique photoluminescence (PL) properties. As synthetic methods gradually develop, many post-functionalization strategies have been developed to enhance the PL of CDs. However, in most cases, the PL enhancement was less than 10-fold with multistep modification processes. In this work, a facile and efficient post-functionalization strategy was successfully applied to enhance the PL intensity of CDs dramatically up to 69 times by surfactants at room temperature for the first time. Furthermore, the mechanism of surfactant-induced PL enhancement of CDs was investigated and in vivo bioimaging was performed. The results demonstrated that electrostatic/non-electrostatic interactions between CDs and surfactants could effectively lower the vibration and rotation of CDs, increase radiative decay processes and, thus, enhance the PL of CDs. This finding may provide new insights into the strategies for enhancing the PL of CDs, further broadening their potential applications.

4.
J Colloid Interface Sci ; 526: 302-311, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29747042

RESUMO

As phototheranostic agents, carbon dots (CDs), have recently drawn considerable attention due to their excellent physicochemical properties. However, the complex synthetic route and high-cost of CDs greatly limit their practical application. To address this issue, given their nearly infinite supply from nature, Hypocrella bambusae is used as the precursor for the preparation of CDs in this study. The obtained Hypocrella bambusae CDs (HBCDs) possess good water solubility, broad absorption (350-800 nm), red-light emission (maximum peak at 610 nm), and low biotoxicity. Moreover, HBCDs can highly generate 1O2 (0.38) and heat (27.6%) under 635 nm laser irradiation. These excellent properties of HBCDs capacitate them to be utilized for bimodal fluorescence/photoacoustic imaging-guided synergistic photodynamic therapy (PDT)/photothermal therapy (PTT). This work provides a new candidate for tumor treatment with the combination of PDT and PTT, and explores a novel approach for the preparation of CD-based phototheranostic agents with natural biomass as raw carbon sources.


Assuntos
Ascomicetos/química , Carbono/química , Hipertermia Induzida/métodos , Nanopartículas , Neoplasias , Imagem Óptica/métodos , Técnicas Fotoacústicas/métodos , Fotoquimioterapia/métodos , Animais , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Adv Mater ; 30(13): e1706090, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29436031

RESUMO

Recent studies indicate that carbon dots (CDs) can efficiently generate singlet oxygen (1 O2 ) for photodynamic therapy (PDT) of cancer. However, the hypoxic tumor microenvironment and rapid consumption of oxygen in the PDT process will severely limit therapeutic effects of CDs due to the oxygen-dependent PDT. Thus, it is becoming particularly important to develop a novel CD as an in situ tumor oxygenerator for overcoming hypoxia and substantially enhancing the PDT efficacy. Herein, for the first time, magnetofluorescent Mn-CDs are successfully prepared using manganese(II) phthalocyanine as a precursor. After cooperative self-assembly with DSPE-PEG, the obtained Mn-CD assembly can be applied as a smart contrast agent for both near-infrared fluorescence (FL) (maximum peak at 745 nm) and T1 -weighted magnetic resonance (MR) (relaxivity value of 6.97 mM-1 s-1 ) imaging. More interestingly, the Mn-CD assembly can not only effectively produce 1 O2 (quantum yield of 0.40) but also highly catalyze H2 O2 to generate oxygen. These collective properties of the Mn-CD assembly enable it to be utilized as an acidic H2 O2 -driven oxygenerator to increase the oxygen concentration in hypoxic solid tumors for simultaneous bimodal FL/MR imaging and enhanced PDT. This work explores a new biomedical use of CDs and provides a versatile carbon nanomaterial candidate for multifunctional nanotheranostic applications.


Assuntos
Carbono/química , Hidrogênio , Nanopartículas , Oxigênio , Fotoquimioterapia , Hipóxia Tumoral
6.
Dalton Trans ; 47(6): 1777-1781, 2018 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-29350743

RESUMO

Herein, novel self-assembled red-emissive C-dots@Au nanoflowers were developed, and they demonstrated efficient photothermal properties under 750 nm laser irradiation. Moreover, C-dots@Au nanoflowers showed the ability of simultaneous photoacoustic and fluorescence imaging. Our study may provide a novel strategy for the efficient phototherapy of cancer cells based on C-dots.


Assuntos
Carbono/química , Nanopartículas/química , Nanotecnologia , Fototerapia/métodos , Carbono/uso terapêutico , Ouro/química , Células HeLa , Humanos , Modelos Moleculares , Conformação Molecular
8.
Mol Brain ; 10(1): 29, 2017 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-28673309

RESUMO

Studies have implied that the circadian oscillation of mitogen-activated protein kinase (MAPK) signal pathways is crucial for hippocampus-dependent memory. NF1 mouse models (Nf1 heterozygous null mutants; Nf1 +/-) displayed enhanced MAPK activity in the hippocampus and resulted in memory deficits. We assumed a link between MAPK pathways and hippocampal rhythmic oscillations, which have never been explored in Nf1 +/- mice. We demonstrated that the level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation in Nf1 +/- mice were significantly higher at nighttime than at daytime. Moreover, the in vivo recording revealed that for the Nf1 +/- group, the power spectral density of theta rhythm significantly decreased and the firing rates of pyramidal neurons increased. Our results indicated that the hippocampal MAPK oscillation and theta rhythmic oscillations in Nf1 +/- mice were disturbed and hinted about a possible mechanism for the brain dysfunction in Nf1 +/- mice.


Assuntos
Ritmo Circadiano , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hipocampo/enzimologia , Hipocampo/fisiopatologia , Neurofibromina 1/genética , Ritmo Teta/fisiologia , Potenciais de Ação/fisiologia , Animais , Masculino , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Fosforilação
9.
Psychiatry Res ; 253: 398-400, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28454051

RESUMO

This study was intended to ascertain whether SNPs in dopaminergic and serotoninergic pathway genes SLC6A2, SLC6A3 and DRD2 are associated with schizophrenia in Han Chinese people. We conducted a case-control study by genotyping 7 SNPs of the three genes in 1034 schizophrenia patients and 1034 controls. No significant difference in the allelic or genotypic frequency was detected between cases and controls despite one positive haplotype (rs1362621-rs2242446-rs5564). Stratified analysis of gender and gene-gene interaction analysis showed no positive results. In summary, our study denies the major role of these SNPs within the three genes for schizophrenia in Han Chinese.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/genética , Receptores de Dopamina D2/genética , Esquizofrenia/genética , Adulto , Alelos , Estudos de Casos e Controles , China , Epistasia Genética , Feminino , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
10.
Adv Healthc Mater ; 6(12)2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28383807

RESUMO

Self-assembly "activated" carbon dot photosensitizer: a robust, NIR-light responsive, and vein injectable carbon dot nanosphere (CDNS) photosensitizer with 1 O2 quantum yield of 0.45 under 671 nm laser irradiation has been developed through self-assembly using individual CD as building units. This study develops the biomedical applications of CD, highlights the self-assembly for designing well-defined CD-based photosensitizers, and promotes future explorations of this CDNS photosensitizer in nanomedical and clinical applications.


Assuntos
Carbono/química , Raios Infravermelhos , Nanosferas/química , Fármacos Fotossensibilizantes/farmacologia , Veias/efeitos dos fármacos , Animais , Peso Corporal , Linhagem Celular Tumoral , Espectroscopia de Ressonância de Spin Eletrônica , Injeções , Camundongos Nus , Nanosferas/ultraestrutura , Fármacos Fotossensibilizantes/administração & dosagem , Fatores de Tempo
14.
Neurosci Lett ; 635: 39-43, 2016 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-27756686

RESUMO

Schizophrenia (SZ) and major depressive disorder (MDD) are two common severe mental disorders that have arisen to public awareness in recent years. Serotonin (5-HT) receptors have been implicated in the pathophysiology of psychiatric disorders especially in MDD and SZ. The aim of this study is to explore whether the variants in the 5-HT1A and 5-HT2A gene are susceptible to SZ or MDD in the Chinese Han population. Five SNPs (Single Nucleotide Polymorphisms) (rs1364043, rs10042486, rs6313, rs6311, rs17289304) in these genes were genotyped from 752 SZ patients, 568 MDD patients, and 846 normal controls of Chinese Han origin. The results showed that the 5-HT1A rs10042486 was significantly associated with SZ (Pallele=0.0369, Pgenotype=0.0098). Moreover, the haplotype (C-T) composed of rs10042486 and rs1364043 showed significant difference between SZ cases and healthy controls (P=0.0302) while another haplotype (T-G) was significant for MDD (P=0.0247). Our study is the first to suggest a positive association of the 5-HT1A gene with SZ in the Han Chinese population.


Assuntos
Transtorno Depressivo Maior/genética , Receptor 5-HT1A de Serotonina/genética , Receptor 5-HT2A de Serotonina/genética , Esquizofrenia/genética , Adulto , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
15.
Psychiatry Res ; 245: 361-364, 2016 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-27591410

RESUMO

Schizophrenia is a highly heritable psychiatric disorder often associated with dopamine-related genetic variations. Thus, we performed a case-control study in 1504 Han Chinese population to evaluate the association of DRD1, DRD2 and DRD3 polymorphisms with schizophrenia. No statistically significant difference in allelic or genotypic frequency was found between schizophrenia and control subjects. Strong positive linkage disequilibrium was detected among the SNPs within DRD1 and DRD2. However, no positive haplotype distribution was found to be associated with schizophrenia. Our results indicated that DRD1, DRD2 and DRD3 may not be the susceptibility genes for schizophrenia in the Chinese Han population.


Assuntos
Predisposição Genética para Doença , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/genética , Receptores de Dopamina D3/genética , Esquizofrenia/genética , Adulto , Estudos de Casos e Controles , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco
16.
Sci Rep ; 6: 32935, 2016 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-27609090

RESUMO

There is an increasing risk of mental disorders, such as acute stress disorder (ASD), post-traumatic stress disorder (PTSD) and depression among survivors who were trapped in rubble during earthquake. Such long-term impaction of a single acute restraint stress has not been extensively explored. In this study, we subjected mice to 24-hour-restraint to simulate the trapping episode, and investigated the acute (2 days after the restraint) and long-term (35 days after the restraint) impacts. Surprisingly, we found that the mice displayed depression-like behaviors, decreased glucose uptake in brain and reduced adult hippocampal neurogenesis 35 days after the restraint. Differential expression profiling based on microarrays suggested that genes and pathways related to depression and other mental disorders were differentially expressed in both PFC and hippocampus. Furthermore, the depression-like phenotypes induced by 24-hour-restraint could be reversed by fluoxetine, a type of antidepressant drug. These findings demonstrated that a single severe stressful event could produce long-term depressive-like phenotypes. Moreover, the 24-hour-restraint stress mice could also be used for further studies on mood disorders.


Assuntos
Comportamento Animal , Encéfalo/fisiopatologia , Depressão/etiologia , Depressão/patologia , Animais , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Camundongos , Restrição Física
17.
Mol Brain ; 9(1): 50, 2016 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-27160396

RESUMO

BACKGROUND: Studies have indicated that depressive disorders are observed frequently in dentists. It's suggested that dentists encounter numerous sources of stress in their professional career. We noticed that the noises in dental environments are very unpleasant. The animal modeling studies suggested that stressful noise could produce depressive-like phenotypes in rodent animals. We hypothesize that the dental noise may be one of the primary stressors causing depressive disorders in dentists. RESULTS: We treated C57BL/6 mice with programmatically played wide-spectrum dental noise for 8 h/day at 75 ± 10 dB SPL level for 30 days, and then tested the behaviors. After exposure to dental noise, animals displayed the depressive-like phenotypes, accompanied by inhibition of neurogenesis in hippocampus. These deficits were ameliorated by orally administered with antidepressant fluoxetine. CONCLUSIONS: Our results suggested that dental noise could be one of the primary stressors for the pathogenesis of depressive disorders and the dental noise mouse model could be used in further depression studies.


Assuntos
Odontologia , Depressão/etiologia , Ruído/efeitos adversos , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Comportamento Animal , Comportamento de Escolha , Depressão/complicações , Depressão/tratamento farmacológico , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Camundongos Endogâmicos C57BL , Neurogênese/efeitos dos fármacos , Fenótipo , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológico , Sacarose , Ganho de Peso/efeitos dos fármacos
19.
Neurosci Lett ; 604: 109-12, 2015 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-26254163

RESUMO

Schizophrenia is a severe and complex mental disorder with high heritability. There is an evidence that metabotropic glutamate receptors (GRM) are associated with schizophrenia. GRM7 has been identified as a candidate gene for many psychiatric disorders especially schizophrenia. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in GRM7 were associated with schizophrenia. Four SNPs (rs9814881, rs13353402, rs9870680 and rs1531939) were genotyped in 1034 schizophrenic patients and 1034 healthy controls of Chinese Han origin. The results showed that the two SNPs rs13353402 and rs1531939 demonstrated significant difference between schizophrenic patients and control subjects in allele frequencies (rs13353402: P value=0.0307, rs1531939: P value=0.0328, respectively). Nevertheless, there was no significant discrepancies in genotype distribution. In summary, our results indicate that the GRM7 SNPs rs13353402 and rs1531939 might be associated with schizophrenia in Chinese Han population.


Assuntos
Receptores de Glutamato Metabotrópico/genética , Esquizofrenia/genética , Adulto , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
20.
Artigo em Inglês | MEDLINE | ID: mdl-25152196

RESUMO

OBJECTIVE: Bipolar disorder (BPD) is a serious and common mental disorder with high heritability. The serotonergic system is known to be implicated in the etiology of the disorder. Tryptophan hydroxylase isoform-2 (TPH2), which controls the synthesis of serotonin in the brain, has been suggested as a candidate gene for BDP. The aim of this study was to examine the association between the polymorphisms in TPH2 and BPD. METHODS: We conducted a case-control study by genotyping six SNPs (rs10784941, rs1386494, rs2171363, rs4760816, rs1386486, and rs1872824) in 506 bipolar patients and 507 controls of Chinese Han origin. RESULTS: rs10784941 was not in the Hardy-Weinberg equilibrium and therefore excluded from further analysis. rs1386486 and rs1872824 showed statistically significant differences between cases and controls in genotype frequencies (rs1386486: p=0.043351; rs1872824: p=0.016563), but no association in allele frequencies. Strong LD was found among rs1386494, rs2171363 and rs4760816, but no positive association with BPD was found for haplotypes. CONCLUSION: Our results indicate that in the Han Chinese population TPH2 may be a potential susceptibility gene for bipolar disorder. Further studies are needed to validate this association.


Assuntos
Transtorno Bipolar/etnologia , Transtorno Bipolar/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Triptofano Hidroxilase/genética , Adulto , Grupo com Ancestrais do Continente Asiático/etnologia , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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