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1.
Phys Chem Chem Phys ; 26(15): 11429-11435, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38563510

RESUMO

The deposition and intercalation of metal atoms can induce superconductivity in monolayer and bilayer graphenes. For example, it has been experimentally proved that Li-deposited graphene is a superconductor with critical temperature Tc of 5.9 K, Ca-intercalated bilayer graphene C6CaC6 and K-intercalated epitaxial bilayer graphene C8KC8 are superconductors with Tc of 2-4 K and 3.6 K, respectively. However, the Tc of them are relatively low. To obtain higher Tc in graphene-based superconductors, here we predict a new Ca-intercalated bilayer graphene C2CaC2, which shows higher Ca concentration than the C6CaC6. It is proved to be thermodynamically and dynamically stable. The electronic structure, electron-phonon coupling (EPC) and superconductivity of C2CaC2 are investigated based on first-principles calculations. The EPC of C2CaC2 mainly comes from the coupling between the electrons of C-pz orbital and the high- and low-frequency vibration modes of C atoms. The calculated EPC constant λ of C2CaC2 is 0.75, and the superconducting Tc is 18.9 K, which is much higher than other metal-intercalated bilayer graphenes. By further applying -4% biaxial compressive strain to C2CaC2, the Tc can be boosted to 26.6 K. Thus, the predicted C2CaC2 provides a new platform for realizing superconductivity with the highest Tc in bilayer graphenes.

2.
Acta Pharmacol Sin ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982150

RESUMO

Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer's disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aß and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD. This work has shown that ErbB4 deficiency increased the burden of Aß, impaired GABAergic transmission, and disrupted the E/I balance of mitral and tufted cells (M/Ts) in the OB, ultimately resulting in olfactory dysfunction in young adult APP/PS1 mice. NRG1 could enhance GABAergic transmission, rescue E/I imbalance in M/Ts, and alleviate olfactory dysfunction in young adult APP/PS1 mice. OB: olfactory bulb, E/I: excitation/inhibition, Pr: probability of release, PV: parvalbumin interneurons, Aß: ß-amyloid, GABA: gamma-aminobutyric acid.

3.
Int J Mol Sci ; 25(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38338913

RESUMO

DNA methylation and chromatin accessibility play important roles in gene expression, but their function in subgenome expression dominance remains largely unknown. We conducted comprehensive analyses of the transcriptome, DNA methylation, and chromatin accessibility in liver and muscle tissues of allotetraploid common carp, aiming to reveal the function of epigenetic modifications in subgenome expression dominance. A noteworthy overlap in differential expressed genes (DEGs) as well as their functions was observed across the two subgenomes. In the promoter and gene body, the DNA methylation level of the B subgenome was significantly different than that of the A subgenome. Nevertheless, differences in DNA methylation did not align with changes in homoeologous biased expression across liver and muscle tissues. Moreover, the B subgenome exhibited a higher prevalence of open chromatin regions and greater chromatin accessibility, in comparison to the A subgenome. The expression levels of genes located proximally to open chromatin regions were significantly higher than others. Genes with higher chromatin accessibility in the B subgenome exhibited significantly elevated expression levels compared to the A subgenome. Contrastingly, genes without accessibility exhibited similar expression levels in both subgenomes. This study contributes to understanding the regulation of subgenome expression dominance in allotetraploid common carp.


Assuntos
Carpas , Metilação de DNA , Animais , Carpas/genética , Genoma de Planta , Cromatina/genética , Poliploidia , Regulação da Expressão Gênica de Plantas
4.
Phys Chem Chem Phys ; 25(4): 2875-2881, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36625788

RESUMO

Monolayer biphenylene is a new two-dimensional (2D) carbon allotrope, which has been experimentally synthesized and theoretically predicted to show superconductivity. In this work, we investigate functionalized biphenylene with the adsorption of Li. The superconducting critical temperature (Tc) can be pushed from 0.59 K up to 3.91 K after Li adsorption. Our calculations confirm that the adsorption pushes the peak showing a high electronic density of states closer to the Fermi level, which usually leads to a larger Tc. Furthermore, the application of biaxial tensile strain can soften phonons and further enhance the Tc up to 15.86 K in Li-deposited biphenylene. Interestingly, a pair of type-II Dirac cones below the Fermi level has been observed, expanding the range of Dirac materials. It suggests that monolayer biphenylene deposited with Li may be a material with potential applications and improves the understanding of Dirac-type superconductors.

5.
Acta Pharmacol Sin ; 44(2): 321-331, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35655094

RESUMO

Metabolic cardiomyopathy (MC) is characterized by intracellular lipid accumulation and utilizing fatty acids as a foremost energy source, thereby leading to excess oxidative stress and mitochondrial dysfunction. There is no effective therapy available yet. In this study we investigated whether defective mitophagy contributed to MC and whether urolithin A (UA), a naturally occurring microflora-derived metabolite, could protect against MC in experimental obese mice. Mice were fed high fat diet for 20 weeks to establish a diet-induced obese model. We showed that mitochondrial autophagy or mitophagy was significantly downregulated in the heart of experimental obese mice. UA (50 mg·kg-1·d-1, for 4 weeks) markedly activated mitophagy and ameliorated MC in obese mice by gavage. In PA-challenged H9C2 cardiomyocytes, UA (5 µM) significantly increased autophagosomes and decreased autolysosomes. Furthermore, UA administration rescued PINK1/Parkin-dependent mitophagy and relieved mitochondrial defects in the heart of obese mice, which led to improving cardiac diastolic function and ameliorating cardiac remodelling. In PA-challenged primarily isolated cardiomyocytes, both application of mitophagy inhibitor Mdivi-1 (15 µM) and silencing of mitophagy gene Parkin blunted the myocardial protective effect of UA. In summary, our data suggest that restoration of mitophagy with UA ameliorates symptoms of MC, which highlights a therapeutic potential of UA in the treatment of MC.


Assuntos
Cardiomiopatias , Mitofagia , Camundongos , Animais , Camundongos Obesos , Proteínas Quinases/metabolismo , Cardiomiopatias/metabolismo , Miócitos Cardíacos/metabolismo , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
6.
Acta Pharmacol Sin ; 44(5): 940-953, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36357669

RESUMO

Dopaminergic neuron degeneration is a hallmark of Parkinson's disease (PD). We previously reported that the inactivation of von Hippel‒Lindau (VHL) alleviated dopaminergic neuron degeneration in a C. elegans model. In this study, we investigated the specific effects of VHL loss and the underlying mechanisms in mammalian PD models. For in vivo genetic inhibition of VHL, AAV-Vhl-shRNA was injected into mouse lateral ventricles. Thirty days later, the mice received MPTP for 5 days to induce PD. Behavioral experiments were conducted on D1, D3, D7, D14 and D21 after the last injection, and the mice were sacrificed on D22. We showed that knockdown of VHL in mice significantly alleviated PD-like syndromes detected in behavioral and biochemical assays. Inhibiting VHL exerted similar protective effects in MPP+-treated differentiated SH-SY5Y cells and the MPP+-induced C. elegans PD model. We further demonstrated that VHL loss-induced protection against experimental parkinsonism was independent of hypoxia-inducible factor and identified the Dishevelled-2 (DVL-2)/ß-catenin axis as the target of VHL, which was evolutionarily conserved in both C. elegans and mammals. Inhibiting the function of VHL promoted the stability of ß-catenin by reducing the ubiquitination and degradation of DVL-2. Thus, in vivo overexpression of DVL-2, mimicking VHL inactivation, protected against PD. We designed a competing peptide, Tat-DDF-2, to inhibit the interaction between VHL and DVL-2, which exhibited pharmacological potential for protection against PD in vitro and in vivo. We propose the therapeutic potential of targeting the interaction between VHL and DVL-2, which may represent a strategy to alleviate neurodegeneration associated with PD.


Assuntos
Proteínas Desgrenhadas , Doença de Parkinson , Proteína Supressora de Tumor Von Hippel-Lindau , Animais , Humanos , Camundongos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , beta Catenina/metabolismo , Caenorhabditis elegans/metabolismo , Modelos Animais de Doenças , Proteínas Desgrenhadas/efeitos dos fármacos , Proteínas Desgrenhadas/metabolismo , Dopamina/farmacologia , Neurônios Dopaminérgicos/metabolismo , Mamíferos , Camundongos Endogâmicos C57BL , Neuroblastoma/metabolismo , Doença de Parkinson/metabolismo , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/metabolismo , Ubiquitinação/efeitos dos fármacos , Ubiquitinação/genética , Proteína Supressora de Tumor Von Hippel-Lindau/antagonistas & inibidores , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo
7.
Psychol Health Med ; 28(8): 2156-2168, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35477332

RESUMO

A range of studies have shown that prenatal maternal stress (PNMS) exposure is associated with offspring autistic-like behaviors, however the potential pathways remain unexplored. This study aimed to evaluate the mediating role of parent-child interactions in early life in the association between PNMS exposure and preschoolers' autistic-like behaviors. Data from 65,928 child-parent dyads were obtained via a primary caregiver-reported questionnaire administered as part of the Longhua Child Cohort Study. To strengthen confidence in the reliability of the results, the analyses were initially conducted on a random selection of 70% of the total sample, and then validated on the remaining 30% of the sample. Analysis of covariance and multiple linear models were employed to estimate the associations between PNMS exposure, parent-child interactions in early life, and children's autistic-like behaviors. The results showed that PNMS exposure was positively associated with the presence of autistic-like behaviors at preschool age. The total indirect effect of the frequency of positive parent-child interactions in early life accounted for 9.69% or 8.99% of the variance of the association. Our findings indicate that parent-child interactions in early life might function as potential mediators of the association between PNMS and the increased risk of offspring autistic-like behaviors.

8.
Pharmacol Res ; 175: 105983, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34822972

RESUMO

Angiogenesis plays an important role in the growth and metastasis of solid tumors including melanoma. Inhibiting tumor-associated angiogenesis is a tactic in treating melanoma. Dioscin restrains angiogenesis in colon tumor and has anti-melanoma effects in cell and animal models. In a previous study, we found that dioscin inhibits Src/STAT3 signaling in melanoma cells. Activation of the Src/STAT3 pathway has been shown to promote tumor angiogenesis. This study aimed to determine whether dioscin's anti-melanoma effects is related to inhibiting Src/STAT3 signaling-mediated angiogenesis. In a B16F10 allograft mouse model, we found that dioscin inhibited melanoma growth and angiogenesis. To exclude the impact of tumor growth on angiogenesis, a chicken chorioallantoic membrane (CAM) model was used to verify the anti-angiogenic effect of dioscin. Results showed that dioscin suppressed vessel formation in CAM. To determine if tumor secreted pro-angiogenic cytokines are involved in the anti-angiogenic effect of dioscin, conditioned media from dioscin-treated A375 melanoma cells were used to culture human umbilical vein endothelial cells (HUVECs), and tube formation was monitored. It was observed that the tube formation of HUVECs was inhibited. Mechanistic studies revealed that dioscin inhibited the activation of Src and STAT3, and lowered mRNA and protein levels of STAT3 transcriptionally-regulated genes, in B16F10 melanomas. ELISA assays showed that dioscin decreased the secretion of MMP-2, MMP-9 and VEGF from A375 cells. Over-activation of STAT3 lessened the effects of dioscin in decreasing the secretion of pro-angiogenic cytokines from melanoma cells, and in inhibiting tube formation of HUVECs cultured with conditioned media from melanoma cell cultures. In summary, we for the first time demonstrated that inhibiting Src/STAT3 signaling-mediated angiogenesis is involved in the anti-melanoma effects of dioscin. This study provides further pharmacological groundwork for developing dioscin as an anti-melanoma agent.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Diosgenina/análogos & derivados , Melanoma Experimental/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Fator de Transcrição STAT3/antagonistas & inibidores , Quinases da Família src/antagonistas & inibidores , Inibidores da Angiogênese/farmacologia , Animais , Linhagem Celular Tumoral , Diosgenina/farmacologia , Diosgenina/uso terapêutico , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Masculino , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Fator de Transcrição STAT3/metabolismo , Carga Tumoral/efeitos dos fármacos , Quinases da Família src/metabolismo
9.
Indoor Air ; 32(1): e12953, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34738663

RESUMO

Indoor air pollution is a recognized risk factor for a range of negative health outcomes. This study aimed to investigate the association between maternal prenatal exposure to indoor air pollution and the presence of autistic-like behaviors among preschool children. Data were obtained from the Longhua Child Cohort Study in 2017, in which we enrolled a total of 65 317 preschool children. Associations between maternal exposure to four sources of indoor air pollution (e.g., cooking, environmental tobacco smoke (ETS), mosquito coils, and home decoration) during pregnancy and preschool children's autistic traits were analyzed using multivariate logistic regression. Our results showed that maternal exposure to indoor air pollution from four different sources during pregnancy was associated with the presence of children's autistic-like behaviors. There was dose-response relationship between the accumulative exposure to the four different indoor air pollution sources and the risk of autistic-like behaviors. Furthermore, we found a significant additive interaction between prenatal exposure to both cooking and mosquito coil incense on the risk of autistic-like behaviors. Maternal prenatal exposure to the indoor air pollution from four sources might increase with the risk of autistic-like behaviors being present among preschool children, with an additive interaction effect between some pollution sources.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Transtorno Autístico , Efeitos Tardios da Exposição Pré-Natal , Poluentes Atmosféricos/análise , Poluição do Ar , Poluição do Ar em Ambientes Fechados/análise , Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Transtorno Autístico/epidemiologia , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Gravidez , Poluição por Fumaça de Tabaco/efeitos adversos
10.
Cell Biol Int ; 45(11): 2201-2210, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34019714

RESUMO

Hepatocellular carcinoma (HCC) is regarded as one of the most common malignancies worldwide leading to cancer-related death. Long noncoding RNAs (lncRNAs) are a critical modulator affecting HCC progression. Whereas, the pathogenesis of lncRNA RBM5-AS1 in the development of HCC remains unclear. Quantitative RT-PCR or western blot assays were applied to detect the expression of genes and proteins, respectively. The proliferation and metastasis abilities were assessed using Cell counting kit-8 (CCK-8), EdU and transwell assays. RNA immunoprecipitation (RIP) experiment was employed to validate the molecular interactions. RBM5-AS1 is highly expressed in HCC tissues and cell lines, especially in Hep3B and HepG2 cells. RBM5-AS1 knockdown dramatically restrains cell proliferation, invasion and migration of HCC cells. Importantly, RBM5-AS1 acts as an epigenetic regulator to elevate the H3K27me3 level of miR-132/212 promoter regions via recruiting PRC2 (EZH2, SUZ12, EED), and eventually reducing miR-132/212 expressions. The recovery experiments demonstrated that downregulation of miR-132/212 markedly eliminate the antitumor effects mediated by RBM5-AS1 silencing in HCC cells. The data of this work illustrate that RBM5-AS1 acts as an epigenetic regulator to promote the HCC progression by repressing miR-132/212 expressions, which would provide a new insight for understanding the action mechanism of RBM5-AS1 in HCC development.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , MicroRNAs/genética , Proteínas de Ligação a RNA/genética , Proteínas Supressoras de Tumor/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proteínas de Ligação a DNA/metabolismo , Epigênese Genética/genética , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , RNA Antissenso/genética , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais/genética , Proteínas Supressoras de Tumor/metabolismo
11.
Am J Emerg Med ; 50: 66-70, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34293624

RESUMO

BACKGROUND: This study evaluated the effect of Guo Qing Yi Tang (GQYT) combined with Western medicine cluster therapy on acute pancreatitis (AP). METHODS: A total of 138 AP patients were recruited and divided into the observation group (68 patients) and control group (70 patients). The control group was treated with cluster therapy alone, while the observation group was treated with trans-jejunum feeding of GQYT combined with cluster therapy. Blood samples were taken before the treatment and 24 h, 72 h, and 1 week after the treatment. The serum concentrations of Di amine oxidase(DAO), Endotoxin(ET), D-lactic acid, Intestinal trefoil factor(ITF), MFG-E8, TNF-α, IL-1ß, IL-6, and IL-8 were determined by using spectrophotometry and enzyme-linked immunosorbent assay. The concentrations of urinary lactulose and mannitol (L/M) were determined by high-performance liquid chromatography, and the urinary L/M value was calculated. RESULTS: Compared with the control group, the observation group had shorter hospital stay, faster recovery, significantly lower APACHE II score, and higher complete response rate (94.12%) after 1 week of treatment (P < 0.05). Moreover, the indicators related to intestinal mucosal barrier function (DAO, MFG-8, L/M) and inflammatory cytokines (TNF-α, IL-6, IL-8) were significantly reduced in the observation group after 1 week of treatment (P < 0.05). CONCLUSION: GQYT combined with cluster therapy for the treatment of AP has definite curative effect and rapid onset, reduces the level of inflammatory factors, and improves intestinal mucosal barrier function and APACHE II score. Thus, it has obvious clinical therapeutic advantages and can be used as a new therapeutic regimen for AP.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Pancreatite/tratamento farmacológico , Pancreatite/terapia , APACHE , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Terapia Combinada , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino
12.
Psychol Health Med ; 26(5): 607-620, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33227216

RESUMO

Screen time is becoming increasingly common in daily life. Early and excessive screen use has raised growing concerns for children's neuropsychological development. The purpose of this study was to evaluate the association between exposure to screen time in early life and the presence of autistic-like behaviors among preschool children. 29,461 child-caregiver dyads at kindergartens in Longhua New District of Shenzhen, China, were enrolled in this cross-sectional study. Information concerning socio-demographic characteristics, frequency and duration of children's electronic screen exposure for each year since birth, and autistic-like behaviors (measured by the Autism Behavior Checklist) were collected using a self-administered structured questionnaire completed by the primary caregivers. A series of logistic regression models assessed the association between screen time and autistic-like behaviors. Results indicated that younger initial age, longer daily screen time and longer cumulative years of screen exposure since birth were associated with the presence of autistic-like behaviors at preschool age. The risk was enhanced with the increase of both daily screen time and cumulative years of screen exposure during preschool period. Moreover, the cross-over analysis indicated that the first three years following birth might be a sensitive period for children when screen exposure increases the risk of experiencing autistic-like behaviors. In conclusion, our study implied that screen exposure in early life might increase the occurrence of autistic-like behaviors among preschoolers. These findings support the need for early interventions into preschoolers' screen use, however longitudinal studies are necessary to further confirm the causal relationship between early screen time and the incidence of later autistic-like behaviors among preschool children.


Assuntos
Transtorno Autístico , Tempo de Tela , Transtorno Autístico/epidemiologia , Pré-Escolar , China/epidemiologia , Estudos Transversais , Humanos , Inquéritos e Questionários
13.
Biol Pharm Bull ; 43(8): 1267-1271, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32741948

RESUMO

Primary liver cancer is a lethal cancer. The phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway has been implicated in the pathogenesis of liver cancer. Gomisin N (GN), a lignan isolated from the dried fruits of Schisandra chinensis (Turca.) Baill., has been reported to reduce viability of, and induce apoptosis in, HepG2 liver cancer cells. In preadipocytes, GN was found to inhibit Akt activity. In the present study, Akt signaling-related anti-liver cancer mechanisms of GN were investigated. We confirmed that GN reduces cell viability of, and triggers apoptosis in, more liver cancer cell lines. Mechanistic studies revealed that GN lowers protein levels of phospho-PI3K (p85 tyrosine (Tyr)458), phospho-Akt (serine (Ser)473), and Akt downstream molecules Mcl-1 in HepG2 and HCCLM3 cells. Meanwhile, GN activates mTOR and inhibits ULK1 (a negative downstream effector of mTOR) activities. Activation of mTOR has been reported to suppress ULK1 activity and repress autophagy. Indeed, we observed that GN inhibits autophagy in liver cancer cells. In summary, we for the first time demonstrated that GN inhibits the PI3K-Akt pathway and regulates the mTOR-ULK1 pathway in liver cancer cells.


Assuntos
Antineoplásicos/farmacologia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Lignanas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Fosfatidilinositol 3-Quinase/fisiologia , Compostos Policíclicos/farmacologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Serina-Treonina Quinases TOR/fisiologia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/antagonistas & inibidores , Linhagem Celular Tumoral , Ciclo-Octanos/farmacologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos
14.
Molecules ; 25(4)2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32098371

RESUMO

Excessive food consumption and insufficient exercise lead to the prevalence of metabolic syndrome in modern life, which consequently increases the risk of many chronic diseases. Magnesium lithospermate B (MLB) from Danshen has been demonstrated to improve metabolic changes in high-fat diet-fed rats with metabolic syndrome. In this study, Mg2+ in MLB was successfully replaced with Zn2+ to form zinc lithospermate B (ZLB) complex. MLB (10 mg/kg /day) and ZLB of various concentrations (1, 2.5, 5, and 10 mg/kg/day) were prepared and examined for their therapeutic effects on metabolic syndrome induced in rats fed with a high-fat diet. The results showed that both MLB and ZLB were able to recover or alleviate the abnormal physiological states of high-fat diet-fed rats including weight gain, epididymal fat accumulation, fatty liver, retarded blood lipid and glucose metabolism putatively caused by insulin resistance, and elevated levels of proinflammatory cytokine, leptin, and oxidative stress. In an overall view of the animal study, the effectiveness of ZLB supplementation seemed to be better than that of MLB supplementation for the recovery of high-fat-fed rats from metabolic syndrome.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Síndrome Metabólica/tratamento farmacológico , Zinco/farmacologia , Animais , Glicemia/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Medicamentos de Ervas Chinesas/química , Humanos , Insulina/metabolismo , Leptina/sangue , Lipídeos/sangue , Magnésio/química , Magnésio/farmacologia , Síndrome Metabólica/etiologia , Síndrome Metabólica/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Salvia miltiorrhiza , Aumento de Peso/efeitos dos fármacos , Zinco/química
15.
J Synchrotron Radiat ; 26(Pt 6): 1929-1935, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31721736

RESUMO

X-ray irradiation has been extensively used in recent years as a fabrication step for nanoparticles and nanoparticle systems. A variant of this technique, continuous-flow X-ray irradiation, has recently been developed, and offers three important advantages: precise control of the irradiation dose, elimination of convection effects in the precursor solution, and suitability for large-scale production. Here, the use of this method to fabricate Au nano-meshes of interest as transparent and flexible electrodes for optoelectronics is reported. The study includes extensive characterization of the synthesis parameters and of the product properties, with rather encouraging results.

16.
Pharmacol Res ; 142: 115-126, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30797070

RESUMO

A traditional Chinese medicine (TCM) formula (SL) comprising Sophorae Flos and Lonicerae Japonicae Flos was used for treating melanoma in ancient China. We have previously shown that an ethanolic extract of SL (SLE) possesses anti-melanoma effects and suppresses STAT3 signaling in vitro and in vivo. STAT3 has been linked to the development of melanoma immunosuppressive microenvironment. In this work, we investigated whether SLE inhibits melanoma growth by reprogramming the tumor microenvironment in mouse and co-culture cell models. In B16F10 melanoma-bearing mice, we found that intragastric administration of SLE (1.2 g/kg) dramatically inhibited tumor growth. This observation was associated with the downregulation of protein levels of phospho-STAT3 (Tyr 705) and STAT3-regulated immunosuppressive cytokines, and mRNA levels of STAT3-targeted genes involved in tumor growth and immune evasion. We also observed increased Th, Tc and dendritic cells in the melanomas and spleens in SLE-treated mice compared to that in control mice. In a co-culture system composed of B16F10 cells and mouse primary splenic lymphocytes, it was found that SLE not only inhibited STAT3 activation in B16F10 cells, but also downregulated mRNA levels of STAT3-targeted genes in the splenic lymphocytes. In this co-culture setting, SLE decreased the levels of STAT3-regulated immunosuppressive cytokines, increased the percentages of Th, Tc and dendritic cells as well. Furthermore, effects of SLE on STAT3 phosphorylation, cytokine levels and immune cell subtype percentages were significantly weaker in the B16STAT3C cells (stable cells harboring a constitutively active STAT3 variant STAT3C)/splenic lymphocytes co-culture system than in the B16V cells (cells stably transfected with the empty vector)/splenic lymphocytes co-culture system, indicating that STAT3 over-activation diminishes SLE's effects. In summary, our findings indicate that reprograming the immune microenvironment, partially mediated by inhibiting STAT3 signaling, contributes to the anti-melanoma mechanisms of SLE. This study provides further pharmacological groundwork for developing SLE as a modern agent for melanoma prevention/treatment, and supports the notion that reprograming immunosuppressive microenvironment is a viable anti-melanoma strategy.


Assuntos
Antineoplásicos/farmacologia , Melanoma Experimental/imunologia , Extratos Vegetais/farmacologia , Fator de Transcrição STAT3/imunologia , Neoplasias Cutâneas/imunologia , Sophora , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/uso terapêutico , Técnicas de Cocultura , Flores , Lonicera , Linfócitos , Masculino , Medicina Tradicional Chinesa , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/imunologia , Neovascularização Patológica/patologia , Extratos Vegetais/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Microambiente Tumoral/imunologia
17.
Anesth Analg ; 126(6): 2093-2101, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29381512

RESUMO

BACKGROUND: We demonstrated previously that angiotensin IV (Ang IV) and LVV-hemorphin 7 (LVV-H7) act through the blockade of insulin-regulated aminopeptidase to decrease oxytocin degradation, thereby causing antihyperalgesia at the spinal level in rats. We determined that intrathecal oxytocin can induce significant antihyperalgesia in male rats with inflammation but not in female rats. Thus, we speculate that Ang IV, LVV-H7, and oxytocin can induce antiallodynia, which could be of great therapeutic potential. Because the antihyperalgesia by using these peptides was with sex difference, their possible antiallodynia was examined in male and female mice for comparison. We investigated whether Ang IV, LVV-H7, and oxytocin produce antiallodynia at the spinal level in mice and whether this antiallodynia differs between the sexes. METHODS: Partial sciatic nerve ligation surgery was performed on adult male and female C57BL/6 mice from the same litter (25-30 g). The effects of intrathecal injections of Ang IV (25.8 nmol), LVV-H7 (27.2 nmol), and oxytocin (0.125 or 1.25 nmol) were assessed through the von Frey test 3 days after partial sciatic nerve ligation. RESULTS: Intrathecal injection of Ang IV, LVV-H7, and oxytocin all produced a potent antiallodynia in male mice. However, these antiallodynia effects were either extremely weak or absent in female mice at the same dose. CONCLUSIONS: Intrathecal Ang IV, LVV-H7, and oxytocin can all cause significant antiallodynia in male mice. The Ang IV-, LVV-H7-, and oxytocin-induced antiallodynia effects differed between the sexes at the spinal level in mice.


Assuntos
Angiotensina II/análogos & derivados , Hemoglobinas/administração & dosagem , Hiperalgesia/tratamento farmacológico , Neuralgia/tratamento farmacológico , Ocitocina/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Caracteres Sexuais , Angiotensina II/administração & dosagem , Animais , Feminino , Hiperalgesia/patologia , Injeções Espinhais/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuralgia/patologia , Manejo da Dor/métodos
18.
J Sci Food Agric ; 98(2): 751-757, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28675436

RESUMO

BACKGROUND: The flavor and quality of tea are widely believed to be associated with the pot in which the tea is made. However, this claim is mostly by experiences and lacks solid support from scientific evidence. The current study investigated and compared the chemical compositions of oolong tea made with six different teapot materials, namely Zisha, Zhuni, stainless steel, ceramic, glass and plastic. RESULTS: For each tea sample, polyphenols and caffeine were examined by HPLC-UV, volatile compounds by GC/MS, amino acids by LC/MS and minerals by ICP-MS. The results suggested that tea infusions from Zisha and Zhuni pots contain higher levels of EGC, EGCG and total catechins and less caffeine than those from ceramic, glass and plastic pots and tend to have the lowest total mineral contents, potassium and volatile compounds in tea soup. The statistical differences were not all significant among Zisha, Zhuni and stainless steel pots. CONCLUSION: Based on the overall chemical composition of the tea infusion, Yixing clay pots (Zisha and Zhuni) produce tea infusions that are presumably less bitter and more fragrant and tend to contain more healthful compounds than tea infusions from other pots. The results could partially explain why Yixing clay pots are among the most popular teapots. The beneficial effects of long-term repeated use of these teapots warrants further study. © 2017 Society of Chemical Industry.


Assuntos
Silicatos de Alumínio/química , Cerâmica/química , Vidro/química , Plásticos/química , Aço Inoxidável/química , Chá/química , Argila , Folhas de Planta/química
19.
Reprod Biol Endocrinol ; 13: 93, 2015 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-26276571

RESUMO

BACKGROUND: GJA1 and PTX3 were proposed as gene markers for oocyte and embryo developmental competence, while SERPINE2 was reported to be associated with pregnancy outcome. PRSS35, which is exclusively expressed in the ovary, may be correlated with oocyte competence. This study was conducted to evaluate the correlation of cumulus GJA1, PRSS35, PTX3, and SERPINE2 gene expression levels with oocyte maturation, fertilization, and early embryo development. METHODS: In total, 308 cumulus cell samples separated from individual cumulus-oocyte complex were obtained from 40 patients undergoing the intracytoplasmic sperm injection treatment procedure. Gene expression levels (mRNA levels) in cumulus cells were assessed using quantitative real-time polymerase chain reaction. RESULTS: Gene expression levels of GJA1 and SERPINE2 in cumulus cells surrounding mature oocytes were significantly lower than those in cumulus cells enclosing immature oocytes. PRSS35 mRNA levels in cumulus cells of fertilized oocytes were significantly higher than those in cumulus cells of unfertilized oocytes. GJA1 and SERPINE2 seemed to express higher mRNA levels, while PRSS35 showed lower expression in cumulus cells of oocytes that developed into embryos with good morphology; however, the expression levels of all three genes and PTX3 showed no significant differences between embryos with good or poor morphology. CONCLUSIONS: GJA1 and SERPINE2 represent potential gene markers associated with oocyte maturation. PRSS35 may be correlated with oocyte fertilization potential. However, GJA1, PRSS35, PTX3, and SERPINE2 may not be considered as marker genes for predicting embryo morphology.


Assuntos
Proteína C-Reativa/biossíntese , Conexina 43/biossíntese , Células do Cúmulo/metabolismo , Fertilização/fisiologia , Oogênese/fisiologia , Serina Proteases/biossíntese , Serpina E2/biossíntese , Componente Amiloide P Sérico/biossíntese , Biomarcadores/metabolismo , Proteína C-Reativa/genética , Conexina 43/genética , Células do Cúmulo/citologia , Desenvolvimento Embrionário/fisiologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Gravidez , Serina Proteases/genética , Serpina E2/genética , Componente Amiloide P Sérico/genética , Injeções de Esperma Intracitoplásmicas/métodos
20.
Acta Pharmacol Sin ; 35(7): 937-44, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24989253

RESUMO

AIM: Lithospermate B (LSB) isolated from the traditional Chinese medicine danshen (Salvia miltiorrhiza) is an effective Na(+)/K(+)-ATPase inhibitor and used to treat congestive heart failure. The inhibition of LSB on Na(+)/K(+)-ATPase is potentiated by forming complexes with transition metal ions. Here we investigated the safety and metabolites of different transition metal-LSB complexes in rats. METHODS: LSB complexed with six different transition metal ions (Mg(2+), Zn(2+), Cr(3+), Co(2+), Ni(2+) and Mn(2+)) were prepared. Adult male SD rats were injected with the different metal-LSB complexes (50 mg/kg, iv), and their bile and blood samples were collected. The metabolites of the metal-LSB complexes in the samples were analyzed using mass spectroscopy. RESULTS: In rats injected with LSB complexed with Mg(2+), Zn(2+), Cr(3+), Ni(2+) or Mn(2+), LSB and its four putative metabolites were equivalently detected in their bile samples. Mn(2+)-LSB exhibited distinct metabolite profiles compared with the other four metal-LSB complexes. The four putative metabolites were identified as 3-monomethyl-LSB, 3,3''-dimethyl-LSB, 3,3'''-dimethyl-LSB and 3,3'',3'''-trimethyl-LSB. The tracking of successive bile samples of rats injected with Mg(2+)-LSB, Zn(2+)-LSB and Mn(2+)-LSB concurrently demonstrated that LSB was firstly methylated at position 3, then at position 3'', and, finally, the 3''' hydroxyl group. All rats injected with Co(2+)-LSB died. CONCLUSION: Zn(2+)-LSB, Cr(3+)-LSB, Ni(2+)-LSB or Mn(2+)-LSB produces identical four methylated metabolites of LSB in rats, and seemed to be as safe as LSB or Mg(2+)-LSB.


Assuntos
Complexos de Coordenação/metabolismo , Medicamentos de Ervas Chinesas/metabolismo , Sequestradores de Radicais Livres/metabolismo , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Elementos de Transição/metabolismo , Animais , Complexos de Coordenação/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Sequestradores de Radicais Livres/administração & dosagem , Injeções Intravenosas , Masculino , Metilação , Ratos , Ratos Sprague-Dawley , Salvia miltiorrhiza/química , Elementos de Transição/química
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