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1.
Pediatr Res ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649724

RESUMO

BACKGROUND: Obesity is an important cause for the precocious or early puberty. However, the association between obesity-related loci and the risk of precocious puberty as well as the effect of gene-environment interaction are unclear, especially in the Chinese children population. METHODS: This was a case-control study using baseline data from two cohorts and hospital cases in China. 15 SNPs loci and several environmental factors were included in the analysis of 1201 participants. Chi-square test and logistic regression were used to analyze the association between SNPs and precocious puberty. Additionally, exploratory factor analysis was conducted on 13 environmental variables, and then to explore their interaction with genes on precocious puberty. RESULTS: The effect allele C of rs571312, and G of rs12970134 MC4R were associated with precocious puberty in girls with obesity. Regarding the gene-environment interaction, we found that when girls were in the high socioeconomic status, the rs571312 (OR: 3.996; 95% CI: 1.694-9.423) and rs12970134 (OR: 3.529; 95% CI: 1.452-8.573) risk genotypes had a greater effect on precocious puberty. CONCLUSIONS: The obesity risk gene polymorphisms MC4R rs571312 and rs12970134 were associated with precocious puberty in Chinese girls with obesity, and girls with risk genotypes and high socioeconomic status should be given extra attention. IMPACT: This is the first study that identified the association between rs571312 and rs12970134 of MC4R gene and precocious puberty in Chinese children. We found that when girls were in the high socioeconomic status, the risk genotypes of rs571312 and rs12970134 had a greater effect on precocious puberty. The results of this study have great public health implications. It is recommended that girls who are in high socioeconomic status and have a high genetic risk for early sexual maturity should closely monitor their pubertal development and consider early intervention strategies.

2.
Cereb Cortex ; 33(5): 2174-2182, 2023 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-35567796

RESUMO

Gray matter volume and thickness reductions have been reported in patients with spinocerebellar ataxia type 3 (SCA3), whereas cortical gyrification alterations of this disease remain largely unexplored. Using local gyrification index (LGI) and fractional anisotropy (FA) from structural and diffusion MRI data, this study investigated the cortical gyrification alterations as well as their relationship with white matter microstructural abnormalities in patients with SCA3 (n = 61) compared with healthy controls (n = 69). We found widespread reductions in cortical LGI and white matter FA in patients with SCA3 and that changes in these 2 features were also coupled. In the patient group, the LGI of the left middle frontal gyrus, bilateral insula, and superior temporal gyrus was negatively correlated with the severity of depressive symptoms, and the FA of a cluster in the left cerebellum was negatively correlated with the Scale for the Assessment and Rating of Ataxia scores. Our findings suggest that the gyrification abnormalities observed in this study may account for the clinical heterogeneity in SCA3 and are likely to be mediated by the underlying white matter microstructural abnormalities of this disease.


Assuntos
Doença de Machado-Joseph , Substância Branca , Humanos , Imageamento por Ressonância Magnética , Imagem de Difusão por Ressonância Magnética , Cerebelo , Substância Cinzenta
3.
Gerontology ; 70(6): 572-584, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38461811

RESUMO

INTRODUCTION: Although the relationship between the number of teeth and frailty has been extensively studied, the mediating role of nutrition status in the association between the number of teeth and frailty remains to be clarified. METHODS: A number of 6,664 participants lived in the communities of West China were analyzed in our study. Physical frailty was determined based on the phenotype established by Fried. Nutrition status was evaluated using the Mini Nutrition Assessment-Short Form (MNA-SF) scale. Multiple linear regression was employed to evaluate the direct relationships between the number of teeth, nutrition, and frailty. Mediation models and structural equation model (SEM) pathway analysis were used to test the mediating role of nutrition status in the relationship between the number of teeth and frailty. RESULTS: Among the 6,664 participants aged over 50 years old, the prevalence of frailty was 6.2%. Multiple linear regression analysis showed a significant total relationship between the number of teeth (ß = -0.359, 95% CI: -0.473 to -0.244, p < 0.001) and frailty. After adjusting for MNA-SF scores, the relationship between the number of teeth and frailty remained significant (ß = -0.327, 95% CI: -0.443 to -0.211, p < 0.001), indicating a partial mediating effect of nutrition. Mediation analysis verified that nutrition partially mediated the relationship between the number of teeth and frailty (indirect effect estimate = -0.0121, bootstrap 95% CI: -0.0151 to -0.0092; direct effect estimate = -0.0874, bootstrap 95% CI: -0.1086 to -0.0678) in the fully adjusted model. This mediating effect occurred through influencing weight loss, low level of physical activity, and debility. SEM framework pathway analysis confirmed the association between the number of teeth, nutrition, and frailty. CONCLUSIONS: Our findings demonstrated that frailty was correlated with the number of teeth and poorer nutritional status, with nutrition partially mediating the correlation between the number of teeth and frailty. Our results supported early nutritional evaluation and intervention in oral health to decrease the risk of frailty.


Assuntos
Idoso Fragilizado , Fragilidade , Estado Nutricional , Humanos , Masculino , Feminino , Estudos Transversais , Idoso , Pessoa de Meia-Idade , Fragilidade/epidemiologia , China/epidemiologia , Idoso Fragilizado/estatística & dados numéricos , Avaliação Geriátrica/métodos , Avaliação Nutricional , Perda de Dente/epidemiologia , Idoso de 80 Anos ou mais , Modelos Lineares , Prevalência
4.
BMC Biol ; 21(1): 65, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37013531

RESUMO

BACKGROUND: The protozoan malaria parasite Plasmodium falciparum has a complex life cycle during which it needs to differentiate into multiple morphologically distinct life forms. A key process for transmission of the disease is the development of male and female gametocytes in the human blood, yet the mechanisms determining sexual dimorphism in these haploid, genetically identical sexual precursor cells remain largely unknown. To understand the epigenetic program underlying the differentiation of male and female gametocytes, we separated the two sexual forms by flow cytometry and performed RNAseq as well as comprehensive ChIPseq profiling of several histone variants and modifications. RESULTS: We show that in female gametocytes the chromatin landscape is globally remodelled with respect to genome-wide patterns and combinatorial usage of histone variants and histone modifications. We identified sex specific differences in heterochromatin distribution, implicating exported proteins and ncRNAs in sex determination. Specifically in female gametocytes, the histone variants H2A.Z/H2B.Z were highly enriched in H3K9me3-associated heterochromatin. H3K27ac occupancy correlated with stage-specific gene expression, but in contrast to asexual parasites this was unlinked to H3K4me3 co-occupancy at promoters in female gametocytes. CONCLUSIONS: Collectively, we defined novel combinatorial chromatin states differentially organising the genome in gametocytes and asexual parasites and unravelled fundamental, sex-specific differences in the epigenetic code. Our chromatin maps represent an important resource for future understanding of the mechanisms driving sexual differentiation in P. falciparum.


Assuntos
Malária Falciparum , Parasitos , Animais , Masculino , Feminino , Humanos , Plasmodium falciparum , Histonas/genética , Heterocromatina/genética , Heterocromatina/metabolismo , Montagem e Desmontagem da Cromatina , Diferenciação Sexual/genética , Malária Falciparum/parasitologia , Cromatina/genética , Cromatina/metabolismo , Parasitos/genética , Parasitos/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo
5.
Environ Toxicol ; 39(6): 3448-3472, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38450906

RESUMO

BACKGROUND: Globally, breast cancer, with diverse subtypes and prognoses, necessitates tailored therapies for enhanced survival rates. A key focus is glutamine metabolism, governed by select genes. This study explored genes associated with T cells and linked them to glutamine metabolism to construct a prognostic staging index for breast cancer patients for more precise medical treatment. METHODS: Two frameworks, T-cell related genes (TRG) and glutamine metabolism (GM), stratified breast cancer patients. TRG analysis identified key genes via hdWGCNA and machine learning. T-cell communication and spatial transcriptomics emphasized TRG's clinical value. GM was defined using Cox analyses and the Lasso algorithm. Scores categorized patients as TRG_high+GM_high (HH), TRG_high+GM_low (HL), TRG_low+GM_high (LH), or TRG_low+GM_low (LL). Similarities between HL and LH birthed a "Mixed" class and the TRG_GM classifier. This classifier illuminated gene variations, immune profiles, mutations, and drug responses. RESULTS: Utilizing a composite of two distinct criteria, we devised a typification index termed TRG_GM classifier, which exhibited robust prognostic potential for breast cancer patients. Our analysis elucidated distinct immunological attributes across the classifiers. Moreover, by scrutinizing the genetic variations across groups, we illuminated their unique genetic profiles. Insights into drug sensitivity further underscored avenues for tailored therapeutic interventions. CONCLUSION: Utilizing TRG and GM, a robust TRG_GM classifier was developed, integrating clinical indicators to create an accurate predictive diagnostic map. Analysis of enrichment disparities, immune responses, and mutation patterns across different subtypes yields crucial subtype-specific characteristics essential for prognostic assessment, clinical decision-making, and personalized therapies. Further exploration is warranted into multiple fusions between metrics to uncover prognostic presentations across various dimensions.


Assuntos
Neoplasias da Mama , Análise de Célula Única , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Prognóstico , Glutamina , Antineoplásicos/uso terapêutico , Medicina de Precisão , Genômica , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
6.
Phys Rev Lett ; 131(5): 055001, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37595223

RESUMO

Despite tremendous progress in x-ray free-electron laser (FEL) science over the last decade, future applications still demand fully coherent, stable x rays that have not been demonstrated in existing x-ray FEL facilities. In this Letter, we describe an active Q-switched x-ray regenerative amplifier FEL scheme to produce fully coherent, high-brightness, hard x rays at a high-repetition rate. By using simple electron-beam phase space manipulation, we show this scheme is flexible in controlling the x-ray cavity quality factor Q and hence the output radiation. We report both theoretical and numerical studies on this scheme with a wide range of accelerator, x-ray cavity, and undulator parameters.

7.
Mol Cell Biochem ; 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37310588

RESUMO

Inositol requiring enzyme 1 (IRE1) is generally thought to control the most conserved pathway in the unfolded protein response (UPR). Two isoforms of IRE1, IRE1α and IRE1ß, have been reported in mammals. IRE1α is a ubiquitously expressed protein whose knockout shows marked lethality. In contrast, the expression of IRE1ß is exclusively restricted in the epithelial cells of the respiratory and gastrointestinal tracts, and IRE1ß-knockout mice are phenotypically normal. As research continues to deepen, IRE1α was showed to be tightly linked to inflammation, lipid metabolism regulation, cell death and so on. Growing evidence also suggests an important role for IRE1α in promoting atherosclerosis (AS) progression and acute cardiovascular events through disrupting lipid metabolism balance, facilitating cells apoptosis, accelerating inflammatory responses and promoting foam cell formation. In addition, IRE1α was recognized as novel potential therapeutic target in AS prevention. This review provides some clues about the relationship between IRE1α and AS, hoping to contribute to further understanding roles of IRE1α in atherogenesis and to be helpful for the design of novel efficacious therapeutics agents targeting IRE1α-related pathways.

8.
Analyst ; 148(3): 628-635, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36602005

RESUMO

Biofilms are known to be a great challenge for their anti-bacterial activity as they obstruct drug action for deeper and more thorough bacteria-killing effects. Therefore, developing highly effective antibacterial agents to destroy biofilms and eradicate bacteria is of great significance. Herein, a new type of nanocomposites (denoted as poly(4-cyanostyrene)@silver@polylysine) is proposed, in which polylysine (PLL) could rapidly capture the biofilms and exhibit excellent antibacterial efficacy together with decorated silver (Ag) nanoparticles (NPs) through the charge effect and Ag+ release. Notably, nearly 100% antibacterial rates against Gram-positive bacterium (Staphylococcus aureus, S. aureus) and Gram-negative bacterium (Escherichia coli, E. coli) were achieved. More importantly, poly(4-cyanostyrene) with biological silent Raman imaging capacity is able to illustrate the relationship between antibacterial efficiency and biofilm breakage. In short, such novel nanocomposites can improve the bioavailability of each component and display tremendous potential in antibacterial applications.


Assuntos
Nanopartículas Metálicas , Nanocompostos , Escherichia coli , Prata/farmacologia , Polilisina/farmacologia , Staphylococcus aureus , Antibacterianos/farmacologia , Biofilmes
9.
Opt Express ; 30(9): 14737-14747, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35473211

RESUMO

Underwater optical wireless communication (UOWC) has received increasing attention due to its distinctive characteristics such as high bandwidth and low latency. However, the UOWC link is usually vulnerable to water flow, underwater turbulence and the terminals' own vibration. Thus, to maintain a stable transmission link, an accurate tracking method is essential for UOWC systems. In this paper, a monocular vision aided optical tracking method is proposed, where the deviation degree of the laser spot is employed to realize autonomous real-time alignment of the receiver with the transmitter. Experimental results verify that with the proposed tracking method, the bit error ratio can be ensured to be below the forward error correction (FEC) limit of 3.8×10-3 even under strong disturbance for the practical UOWC system.

10.
Chemphyschem ; 22(9): 894-903, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33538388

RESUMO

Unlike graphene and other 2D materials, borophene is 2D polymorphic with diverse hexagonal holes (HHs)-triangles ratios and the concentrations of HHs are highly substrate dependent. Here, we systematically explored the evolution of boron cluster on Ag(111) surface, BN @Ag(111) (N=1∼36), to understand the nucleation of 2D boron sheet on metal surface. Our calculation showed that, with the size increasing, the structures of most stable BN clusters undergo an evolution from compact triangular lattice, such as double-chains or triple-chains, to the ones with mixed triangular-hexagonal lattices. The first single-HH appears at N=12 and the first double-HH appears at N=27. The stability of large BN clusters with mixed structures is derived from the charge transfer between triangular lattice and the HHs, as well as between the substrates and the BN clusters. Our results provide a deep understanding on the formation of small boron clusters in the initial nucleation stage of borophene growth.

11.
Phys Chem Chem Phys ; 23(3): 2222-2228, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33439169

RESUMO

Understanding the fundamentals of chemical vapor deposition bilayer graphene growth is crucial for its synthesis. By employing density functional theory calculations and classical molecular dynamics simulations, we have investigated the evolution of carbon structures and the kinetics of the adlayer graphene nucleation between the graphene top layer (GTL) and the Ni(111) substrate. Compared to the epitaxial GTL, the weaker interaction between the nonepitaxial GTL and the Ni(111) substrate makes the nucleation of the adlayer more favorable. Furthermore, the defects involving in the adlayer graphene are easier to be healed by adopting the nonepitaxial GTL. Our results agree well with the experimental observation and demonstrate that the adlayer graphene with a high quality can be grown underneath the nonepitaxial GTL on Ni-like substrates.

12.
Hum Brain Mapp ; 41(3): 710-725, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31663232

RESUMO

Although diabetic peripheral neuropathy (DPN) has long been considered a disease of the peripheral nervous system, recent neuroimaging studies have shown that alterations in the central nervous system may play a crucial role in its pathogenesis. Here, we used surface-based morphometry (SBM) and tract-based spatial statistics (TBSS) to investigate gray matter (GM) and white matter (WM) differences between patients with DPN (n = 67, 44 painless and 23 painful) and healthy controls (HCs; n = 88). Compared with HCs, patients with DPN exhibited GM abnormalities in the pre- and postcentral gyrus and in several deep GM nuclei (caudate, putamen, medial pallidum, thalamus, and ventral nuclear). They also exhibited altered WM tracts (corticospinal tract, spinothalamic tract, and thalamocortical projecting fibers). These findings suggest impaired motor and somatosensory pathways in DPN. Further, patients with DPN (particularly painful DPN) exhibited morphological differences in the cingulate, insula, prefrontal cortex, and thalamus, as well as impaired WM integrity in periaqueductal WM and internal and external capsules. This suggests pain-perception/modulation pathways are altered in painful DPN. Intermodal correlation analyses found that the morphological indices of the brain regions identified by the SBM analysis were significantly correlated with the fractional anisotropy of brain regions identified by the TBSS analysis, suggesting that the GM and WM alterations were tightly coupled. Overall, our study showed sensorimotor and pain-related GM and WM alterations in patients with DPN, which might be involved in the development of DPN.


Assuntos
Córtex Cerebral/patologia , Diabetes Mellitus Tipo 2/patologia , Neuropatias Diabéticas/patologia , Substância Cinzenta/patologia , Atividade Motora , Neuralgia/patologia , Distúrbios Somatossensoriais/patologia , Substância Branca/patologia , Adulto , Idoso , Córtex Cerebral/diagnóstico por imagem , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Neuropatias Diabéticas/diagnóstico por imagem , Neuropatias Diabéticas/etiologia , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Neuralgia/diagnóstico por imagem , Neuralgia/etiologia , Neuroimagem , Distúrbios Somatossensoriais/diagnóstico por imagem , Distúrbios Somatossensoriais/etiologia , Substância Branca/diagnóstico por imagem
13.
Phys Rev Lett ; 124(13): 134801, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32302180

RESUMO

Microbunching instability (MBI) driven by beam collective effects is known to be detrimental to high-brightness storage rings, linacs, and free-electron lasers (FELs). One known way to suppress this instability is to induce a small amount of energy spread to an electron beam by a laser heater. The distribution of the induced energy spread greatly affects MBI suppression and can be controlled by shaping the transverse profile of the heater laser. Here, we present the first experimental demonstration of effective MBI suppression using a LG_{01} transverse laser mode and compare the improved results with respect to traditional Gaussian transverse laser mode at the Linac Coherent Light Source. The effects on MBI suppression are characterized by multiple downstream measurements, including longitudinal phase space analysis and coherent radiation spectroscopy. We also discuss the role of LG_{01} shaping in soft x-ray self-seeded FEL emission, one of the most advanced operation modes of a FEL for which controlled suppression of MBI is critical.

14.
Acta Pharmacol Sin ; 41(2): 260-269, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31515528

RESUMO

Timosaponin AIII (Timo AIII) is a natural steroidal saponin isolated from the traditional Chinese herb Anemarrhena asphodeloides Bge with proved effectiveness in the treatment of numerous cancers. However, whether Timo AIII suppresses tumor angiogenesis remains unclear. In the present study, we investigated the antiangiogenesis effects of Timo AIII and the underlying mechanisms in human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish embryos in vivo. We showed that treatment with Timo AIII (0.5-2 µM) partially disrupted the intersegmental vessels (ISVs) and subintestinal vessels (SIVs) growth in transgenic zebrafish Tg(fli-1a: EGFP)y1. Timo AIII (0.5-4 µM) dose-dependently inhibited VEGF-induced proliferation, migration, invasion, and tube formation of HUVECs, but these inhibitory effects were not due to its cytotoxicity. We further demonstrated that Timo AIII treatment significantly suppressed the expression of VEGF receptor (VEGFR) and the phosphorylation of Akt, MEK1/2, and ERK1/2 in HUVECs. Timo AIII treatment also significantly inhibited VEGF-triggered phosphorylation of VEGFR2, Akt, and ERK1/2 in HUVECs. Moreover, we conducted RNA-Seq and analyzed the transcriptome changes in both HUVECs and zebrafish embryos following Timo AIII treatment. The coexpression network analysis results showed that various biological processes and signaling pathways were enriched including angiogenesis, cell motility, cell adhesion, protein serine/threonine kinase activity, transmembrane signaling receptor activity, growth factor activity, etc., which was consistent with the antiangiogenesis effects of Timo AIII in HUVECs and zebrafish embryos. We conclude that the antiangiogenesis effect of Timo AIII is mediated through VEGF/PI3K/Akt/MAPK signaling cascade; Timo AIII potentially exerts antiangiogenesis effect in cancer treatment.


Assuntos
Inibidores da Angiogênese/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Saponinas/farmacologia , Esteroides/farmacologia , Inibidores da Angiogênese/administração & dosagem , Animais , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Saponinas/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Esteroides/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/metabolismo , Peixe-Zebra
15.
Lab Invest ; 98(10): 1320-1332, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29785051

RESUMO

Vascular calcification is a highly regulated biological process similar to bone formation involving osteogenic differentiation of vascular smooth muscle cells (VSMCs). Hyaluronan (HA), a major structural component of the extracellular matrix in cartilage, has been shown to inhibit osteoblast differentiation. However, whether HA affects osteogenic differentiation and calcification of VSMCs remains unclear. In the present study, we used in vitro and ex vivo models of vascular calcification to investigate the role of HA in vascular calcification. Both high and low molecular weight HA treatment significantly reduced calcification of rat VSMCs in a dose-dependent manner, as detected by alizarin red staining and calcium content assay. Ex vivo study further confirmed the inhibitory effect of HA on vascular calcification. Similarly, HA treatment decreased ALP activity and expression of bone-related molecules including Runx2, BMP2 and Msx2. By contrast, inhibition of HA synthesis by 4-methylumbelliferone (4MU) promoted calcification of rat VSMCs. In addition, adenovirus-mediated overexpression of HA synthase 2 (HAS2), a major HA synthase in VSMCs, also inhibited calcification of VSMCs, whereas CRISPR/Cas9-mediated HAS2 knockout promoted calcification of rat A10 cells. Furthermore, we found that BMP2 signaling was inhibited in VSMCs after HA treatment. Recombinant BMP2 enhanced high calcium and phosphate-induced VSMC calcification, which can be blocked by HA treatment. Taken together, these findings suggest that HA inhibits vascular calcification involving BMP2 signaling.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Ácido Hialurônico/metabolismo , Calcificação Vascular/etiologia , Animais , Linhagem Celular , Técnicas de Inativação de Genes , Hialuronan Sintases/genética , Hialuronan Sintases/metabolismo , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Cultura Primária de Células , Ratos Sprague-Dawley , Calcificação Vascular/metabolismo
16.
Toxicol Appl Pharmacol ; 350: 32-42, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29730311

RESUMO

Impaired vascular integrity leads to serious cerebral vascular diseases such as intracerebral hemorrhage (ICH). In addition, high-dose statin therapy is suggested to cause increased ICH risk due to unclear effects of general inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) on the vascular system. Here we evaluated the protective effects of sodium tanshinone IIA sulfonate (STS), which has high efficacy and safety in clinical studies of ischemic stroke, by using atorvastatin (Ator) induced ICH zebrafish embryos and human umbilical vein endothelial cells (HUVECs). By using double transgenic Tg(fli1a:EGFP)y1 & Tg(gata1a:dsRed)sd2 zebrafish, we demonstrated that STS effectively reduced the occurrence and area of hemorrhage induced by Ator in zebrafish and restored impairment in motor function. We further demonstrated that Ator-induced disruption in VE-cadherin (VEC)-containing cell-cell adherens junctions (AJs) in HUVECs by enhancing Src-induced VEC internalization and RhoA/ROCK-mediated cellular contraction. STS inhibited Ator-induced Src activation and subsequent VEC internalization and actin depolymerization near cell borders, reducing lesions between neighboring cells and increasing barrier functions. STS also inhibited the Ator-induced RhoA/ROCK-mediated cellular contraction by regulating downstream LIMK/cofilin and MYPT1/MLC phosphatase signaling. These results showed that STS significantly promoted the stability of cell junctions and vascular integrity. Moreover, we observed that regulations of both Src and RhoA/ROCK are required for the maintenance of vascular integrity, and Src inhibitor (PP2) or ROCK inhibitors (fasudil and H1152) alone could not reduce the occurrence Ator-induced ICH. Taken together, we investigated the underlying mechanisms of Ator-induced endothelial instability, and provided scientific evidences of STS as potential ICH therapeutics by promoting vascular integrity.


Assuntos
Antígenos CD/metabolismo , Atorvastatina/toxicidade , Caderinas/metabolismo , Hemorragia Cerebral/metabolismo , Endotélio Vascular/metabolismo , Fenantrenos/uso terapêutico , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Animais Geneticamente Modificados , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/prevenção & controle , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Fenantrenos/farmacologia , Peixe-Zebra
17.
Pharmacol Res ; 128: 389-398, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29017932

RESUMO

Defects in vascular integrity in cerebrovasculature lead to serious pathologies including hemorrhagic stroke. The stability of cell adhesion junctions and actin-myosin contractile machinery are two major determinants for the integrity of endothelial monolayer. Here we have evaluated the protective effects of tanshinone I (Tan I), a lipophilic compound presents in Salvia miltiorrhiza, against atorvastatin-induced cerebral hemorrhage in zebrafish in vivo, and further dissected the molecular mechanisms in HUVECs. We demonstrated that Tan I protected endothelial integrity by stabilizing cell-cell adhesion junctions via the inhibition of Src-mediated VE-cadherin internalization and subsequent junction-linked actin cytoskeleton depolymerization. In addition, Tan I inhibited ROCK-associated endothelial contractile machinery by dephosphorylating cofilin and MYPT1. These findings identified Tan I as an endothelial stabilizing agent and suggested Tan I as a potential treatment for vascular leakage in hemorrhagic stroke.


Assuntos
Abietanos/farmacologia , Actinas/metabolismo , Antígenos CD/metabolismo , Caderinas/metabolismo , Hemorragia Cerebral/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Miosinas/metabolismo , Substâncias Protetoras/farmacologia , Animais , Animais Geneticamente Modificados , Atorvastatina , Adesão Celular/efeitos dos fármacos , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/prevenção & controle , Embrião não Mamífero , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Peixe-Zebra/genética
18.
J Am Chem Soc ; 138(1): 300-5, 2016 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-26669826

RESUMO

The striking in-plane anisotropy remains one of the most intriguing properties for the newly rediscovered black phosphorus (BP) 2D crystals. However, because of its rather low-energy band gap, the optical anisotropy of few-layer BP has been primarily investigated in the near-infrared (NIR) regime. Moreover, the essential physics that determine the intrinsic anisotropic optical property of few-layer BP, which is of great importance for practical applications in optical and optoelectronic devices, are still in the fancy of theory. Herein, we report the direct observation of the optical anisotropy of few-layer BP in the visible regime simply by using polarized optical microscopy. On the basis of the Fresnel equation, the intrinsic anisotropic complex refractive indices (n-iκ) in the visible regime (480-650 nm) were experimentally obtained for the first time using the anisotropic optical contrast spectra. Our findings not only provide a convenient approach to measure the optical constants of 2D layered materials but also suggest a possibility to design novel BP-based photonic devices such as atom-thick light modulators, including linear polarizer, phase plate, and optical compensator in a broad spectral range extending to the visible window.

19.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 35(11): 1322-5, 2015 Nov.
Artigo em Zh | MEDLINE | ID: mdl-26775478

RESUMO

OBJECTIVE: To evaluate the clinical effectiveness of Yiqi Huoxue Tongyang Xiezhuo Recipe (YHTXR, capable of supplementing qi, activating blood, warming yang, and discharge turbidity) in treating coronary atherosclerotic heart disease (CAHD). and chronic heart failure (CHF) with carotid plaque patients, and to explore new ways of Chinese medicine (CM). METHODS: Totally 69 CAHD-CHF patients of qi deficiency phlegm stasis syndrome (QDPSS) with carotid plaque were recruited in this study using parallel cohort method. They were assigned to the treatment group (35 cases) and the control group (34 cases). Patients in the control group received routine treatment of Western medicine, while those in the treatment group were additionally treated with YHTXR (twice daily). The therapeutic course for all was three months. Cardiac function levels, echocardiography, carotid plaque, blood lipids and safety indicators were observed before and after treatment. RESULTS: After treatment the improvement of cardiac function levels was better in the treatment group than in the control group (P < 0.05). Decreased LDL-C levels were higher in the treatment group than in the control group (P < 0.01). There was statistical difference in left ventricular ejection fraction (LVEF), carotid intima-media thickness (IMT), LDL-C, TC, TG in the treatment group between before and after treatment (P < 0.05). LDL-C and TG also decreased in the control group after treatment (P <0.05). There was no significant difference in the left ventricular ejection fraction, carotid IMT, or TC in the control group between before and after treatment (P > 0.05). There was no significant difference in stroke volume, left ventricular end-diastolic diameter, the area of carotid artery plaque, or HDL-C in the two groups between before and after treatment (P > 0.05). CONCLUSIONS: YHTXR could effectively improve cardiac functions of CAHD-CHF patients of QDPSS with carotid plaque, reduce blood lipids and IMT. It had no significant adverse reactions for elderly patients in short term.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Placa Aterosclerótica/tratamento farmacológico , Espessura Intima-Media Carotídea , Doença das Coronárias , Medicamentos de Ervas Chinesas/farmacologia , Coração , Humanos , Lipídeos , Qi , Função Ventricular Esquerda
20.
Phys Rev Lett ; 112(23): 233001, 2014 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-24972202

RESUMO

Most previous studies have focused on high-order harmonic generation beyond the ionization threshold; mechanisms of below-threshold harmonics are less understood. We schematically study the harmonic emission process in this region by numerically solving the time-dependent Schrödinger equation of an atom in laser fields. We show that, besides the quantum path interference mechanism recently identified, the effects induced by the Coulomb potential also have a critical impact on these harmonics. These mechanisms can be distinguished in the structure of harmonic spectra by changing the laser wavelength and peak intensity. We find that the long quantum orbits can influence lower-order harmonics at a higher laser intensity. In addition, we show that the intensity-dependent steps of harmonic yield can disappear for certain harmonic orders, due to the trapping in the Rydberg states before recombination, which can explain recent experimental observations.

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