Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 64
Filtrar
1.
Nature ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627872

RESUMO

The ability to rapidly adapt to novel situations is essential for survival, and this flexibility is impaired in many neuropsychiatric disorders1. Thus, understanding whether and how novelty prepares, or primes, brain circuitry to facilitate cognitive flexibility has important translational relevance. Exposure to novelty recruits the hippocampus and medial prefrontal cortex (mPFC)2 and may prime hippocampal-prefrontal circuitry for subsequent learning-associated plasticity. Here we show that novelty resets the neural circuits that link the ventral hippocampus (vHPC) and the mPFC, facilitating the ability to overcome an established strategy. Exposing mice to novelty disrupted a previously encoded strategy by reorganizing vHPC activity to local theta (4-12 Hz) oscillations and weakening existing vHPC-mPFC connectivity. As mice subsequently adapted to a new task, vHPC neurons developed new task-associated activity, vHPC-mPFC connectivity was strengthened, and mPFC neurons updated to encode the new rules. Without novelty, however, mice adhered to their established strategy. Blocking dopamine D1 receptors (D1Rs) or inhibiting novelty-tagged cells that express D1Rs in the vHPC prevented these behavioural and physiological effects of novelty. Furthermore, activation of D1Rs mimicked the effects of novelty. These results suggest that novelty promotes adaptive learning by D1R-mediated resetting of vHPC-mPFC circuitry, thereby enabling subsequent learning-associated circuit plasticity.

2.
J Biomed Opt ; 26(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33386708

RESUMO

SIGNIFICANCE: Line scanning-based temporal focusing multiphoton microscopy (TFMPM) has superior axial excitation confinement (AEC) compared to conventional widefield TFMPM, but the frame rate is limited due to the limitation of the single line-to-line scanning mechanism. The development of the multiline scanning-based TFMPM requires only eight multiline patterns for full-field uniform multiphoton excitation and it still maintains superior AEC. AIM: The optimized parallel multiline scanning TFMPM is developed, and the performance is verified with theoretical simulation. The system provides a sharp AEC equivalent to the line scanning-based TFMPM, but fewer scans are required. APPROACH: A digital micromirror device is integrated in the TFMPM system and generates the multiline pattern for excitation. Based on the result of single-line pattern with sharp AEC, we can further model the multiline pattern to find the best structure that has the highest duty cycle together with the best AEC performance. RESULTS: The AEC is experimentally improved to 1.7 µm from the 3.5 µm of conventional TFMPM. The adopted multiline pattern is akin to a pulse-width-modulation pattern with a spatial period of four times the diffraction-limited line width. In other words, ideally only four π / 2 spatial phase-shift scans are required to form a full two-dimensional image with superior AEC instead of image-size-dependent line-to-line scanning. CONCLUSIONS: We have demonstrated the developed parallel multiline scanning-based TFMPM has the multiline pattern for sharp AEC and the least scans required for full-field uniform excitation. In the experimental results, the temporal focusing-based multiphoton images of disordered biotissue of mouse skin with improved axial resolution due to the near-theoretical limit AEC are shown to clearly reduce background scattering.

3.
Int J Nanomedicine ; 15: 6813-6825, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061357

RESUMO

Background: Multidrug-resistant (MDR) bacterial strain is a serious medical problem. Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to many antibiotics and is often associated with several diseases such as arthritis, osteomyelitis, and endocarditis. The development of an alternative treatment for eliminating MDR bacteria such as MRSA has attracted a considerable amount of research attention. Moreover, the development of a material for highly efficient generation of reactive oxygen species (ROS) involving two-photon photodynamic therapy (PDT) is currently desirable. Materials and Methods: We present an example demonstrating that the use of water-soluble C60(OH)30 fullerenol with a 0.89 singlet oxygen quantum yield serving as a photosensitizer in PDT has the superior ability in effectively generating ROS. Results: It has ultra-low energy (228.80 nJ pixel-1) and can perform 900 scans under two-photon excitation (TPE) in the near-infrared region (760 nm) to completely eliminate the MDR species. Furthermore, the favorable two-photon properties are absorption of approximately 760 nm in wavelength, absolute cross-section of approximately 1187.50 Göeppert-Mayer units, lifetime of 6.640 ns, ratio of radiative to nonradiative decay rates of approximately 0.053, and two-photon stability under TPE. Conclusion: This enabled water-soluble C60(OH)30 fullerenol to act as a promising two-photon photosensitizer proceeding with PDT to easily eliminate MDR species.

4.
Int J Nanomedicine ; 15: 6961-6973, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061362

RESUMO

Background: Although graphene quantum dots (GQDs) have received considerable research attention for their applications in various fields, the use of GQDs, such as nitrogen-doped GQDs (N-GQDs) and amino-functionalized N-GQDs (amino-N-GQDs), as photosensitizers to facilitate photodynamic therapy (PDT) has received limited research intention. To address this research gap, this study prepared novel amino-N-GQDs and investigated their properties. Methods: The amino-N-GQDs subjected to two-photon excitation (TPE) exhibited remarkable bactericidal capability in PDT. The bonding compositions of nitrogen and the amino-functionalized group played a critical role in their antimicrobial effects. Results: Compared with amino-group-free N-GQDs and amino-N-free GQDs, the amino-N-GQDs generated a higher amount of reactive oxygen species, demonstrating their superior efficacy for two-photon PDT. Additionally, the intrinsic luminescence properties and high photostability of the amino-N-GQDs demonstrate their suitability as an effective two-photon contrast agent for tracking bacteria during two-photon biomedical imaging. Conclusion: The amino-N-GQD and their remarkable properties may provide an efficient alternative approach for observing and easily eliminating malignant microbes in the future.


Assuntos
Antibacterianos/farmacologia , Meios de Contraste/química , Nitrogênio/farmacologia , Fotoquimioterapia/métodos , Pontos Quânticos/química , Antibacterianos/química , Bacillus subtilis/efeitos dos fármacos , Grafite/química , Luminescência , Nitrogênio/química , Fótons , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia
5.
ACS Nano ; 14(9): 11502-11509, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32790323

RESUMO

In this study, sorted nitrogen-doped graphene quantum dots were prepared and subsequently conjugated with polymers. The synthesized materials exhibited excitation-wavelength-independent photoluminescence emissions ranging from ultraviolet to near-infrared and were 0.9-8.4 nm in size. The materials also exhibited high-photoluminescence quantum yields and excellent two-photon properties. Therefore, in two-photon bioimaging the materials with different emission spectra can be effective two-photon contrast agents. Specific antibodies were used to label organelles in cancer cells and identify nuclear antigens, thereby enabling the simultaneous detection of four targets in cells at a single two-photon excitation wavelength. The sorted nitrogen-doped graphene quantum dot materials were determined to be considerably more advantageous than organic dyes in identifying multiplexed targets, and they can be effective probes in cellular imaging.

6.
Mar Drugs ; 18(8)2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32722176

RESUMO

Our continuous chemical study of a cultured octocoral Briareum stechei led to the isolation of four new briarane diterpenoids, briarenols Q-T (1-4). The structures of new metabolites 1-4 were established by spectroscopic methods, and compounds 3 and 4 were found to inhibit the generation of inducible nitric oxide synthase (iNOS) from RAW 264.7 stimulated by lipopolysaccharides (LPS).

7.
Nanoscale Res Lett ; 15(1): 99, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32378063

RESUMO

We successfully prepared water-soluble fullerenol [C60(OH)46] that exhibited a high singlet oxygen quantum yield and efficiently generated reactive oxygen species. Additionally, the water-soluble C60(OH)46 with a higher composition of exposed hydroxyl groups had superior two-photon stability and characteristics compared with that with a lower composition of such groups. Therefore, the prepared fullerenol can be an effective two-photon photosensitizer. The water-soluble C60(OH)46 had favorable two-photon properties. During two-photon photodynamic therapy, the water-soluble C60(OH)46 had substantial antimicrobial activity against Escherichia coli at an ultralow-energy level of 211.2 nJ pixel-1 with 800 scans and a photoexcited wavelength of 760 nm.

8.
Int J Mol Sci ; 21(8)2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32331302

RESUMO

We fabricated nanomaterials comprising amino-functionalized and nitrogen-doped graphene quantum dots (amino-N-GQDs) and investigated their photostability and intrinsic luminescence in the near-infrared spectrum to determine their suitability as contrast agents in two-photon imaging (TPI). We observed that amino-N-GQDs with a higher amount of bonded nitrogen and amino-functionalized groups (6.2%) exhibited superior two-photon properties to those with a lower amount of such nitrogen and groups (4.9%). These materials were conjugated with polymers containing sulfur (polystyrene sulfonate, PSS) and nitrogen atoms (polyethylenimine, PEI), forming amino-N-GQD-PSS-PEI specimens (amino-N-GQD-polymers). The polymers exhibited a high quantum yield, remarkable stability, and notable two-photon properties and generated no reactive oxygen species, rendering them excellent two-photon contrast agents for bioimaging. An antiepidermal growth factor receptor (AbEGFR) was used for labeling to increase specificity. Two-photon imaging (TPI) of amino-N-GQD (6.2%)-polymer-AbEGFR-treated A431 cancer cells revealed remarkable brightness, intensity, and signal-to-noise ratios for each observation at a two-photon excitation power of 16.9 nJ pixel-1 under 30 scans and a three-dimensional (3D) depth of 105 µm, indicating that amino-N-GQD (6.2%)-polymer-AbEGFR-treated cells can achieve two-photon luminescence with 71 times less power required for two-photon autofluorescence (1322.8 nJ pixel-1 with 500 scans) of similar intensity. This economy can minimize photodamage to cells, rendering amino-N-GQD-polymers suitable for noninvasive 3D bioimaging.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32316516

RESUMO

Previous studies reflect a high prevalence of depressive symptoms among Taiwanese adolescents (ages 13-18), but there is an absence of literature related to the risk of depression of children in Taiwan (ages 6-12), particularly among potentially vulnerable subgroups. To provide insight into the distribution of depressive symptoms among children in rural Taiwan and measure the correlation between academic performance, we conducted a survey of 1655 randomly selected fourth and fifth-grade students at 92 sample schools in four relatively low-income counties or municipalities. Using the Center for Epidemiological Studies-Depression Scale (CES-D) we assessed the prevalence of depressive symptoms in this sample, in addition to collecting other data, such as performance on a standardized math test as well as information on a number of individual and household characteristics. We demonstrate that the share of children with clinically significant symptoms is high: 38% of the students were at risk of general depression (depression score ≥ 16) and 8% of the students were at risk of major depression (depression score > 28). The results of the multivariate regression and heterogeneous analysis suggest that poor academic performance is closely associated with a high prevalence of depressive symptoms. Among low-performing students, certain groups were disproportionately affected, including girls and students whose parents have migrated away for work. Results also suggest that, overall, students who had a parent who was an immigrant from another country were at greater risk of depression. These findings highlight the need for greater resource allocation toward mental health services for elementary school students in rural Taiwan, particularly for at-risk groups.


Assuntos
Desempenho Acadêmico , Depressão , População Rural , Estudantes/psicologia , Criança , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Masculino , Prevalência , Taiwan/epidemiologia
10.
Vaccine ; 38(22): 3839-3846, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32284272

RESUMO

BACKGROUND: Quadrivalent influenza vaccines are particularly valuable during seasons in which a mismatch occurs between the predicted influenza B lineage for the trivalent influenza vaccine and the circulating strain. This study evaluated the immunogenicity and safety of a quadrivalent inactivated influenza vaccine AdimFlu-S manufactured in Taiwan for the 2016-2017 influenza season in healthy children. METHODS: A total of 174 healthy children aged 3 to 17 years old were separated into 3 groups (Group A: 3-8 years old, vaccine naïve; Group B: 3-8 years old, vaccine non-naïve; Group C: 9-17 years old, any vaccine status). Sera was collected pre and post vaccination for each participant. A hemagglutination inhibition (HAI) assay was utilized to calculate geometric mean titer (GMT), seroprotection rate, and seroconversion rate. RESULTS: All enrolled participants completed the study. For the four vaccine strains four weeks after the last vaccination, geometric mean titer ratios (GMTRs) were between 2.9 and 20.9, seroconversion rates were between 42.9% and 90.9%, and seroprotection rates were all above 96.4%. This achieved all immunogenicity endpoints and fulfilled the criteria of the European Medical Agency's Committee for Medicinal Products for Human Use (CHMP). No serious adverse events (AEs) were reported during the follow-up period of 6 months. CONCLUSION: This quadrivalent influenza vaccine is demonstrated to be well tolerated and displays robust immunogenicity for each influenza strain. This could potentially improve protection against the antigenically distinct B/Yamagata and B/Victoria lineages.

11.
Sci Rep ; 10(1): 647, 2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959776

RESUMO

Accumulating evidence suggests AKT1 and DRD2-AKT-GSK3 signaling involvement in schizophrenia. AKT1 activity is also required for lithium, a GSK3 inhibitor, to modulate mood-related behaviors. Notably, GSK3 inhibitor significantly alleviates behavioral deficits in Akt1-/- female mice, whereas typical/atypical antipsychotics have no effect. In agreement with adjunctive therapy with lithium in treating schizophrenia, our data mining indicated that the average utilization rates of lithium in the Taiwan National Health Insurance Research Database from 2002 to 2013 are 10.9% and 6.63% in inpatients and outpatients with schizophrenia, respectively. Given that lithium is commonly used in clinical practice, it is of great interest to evaluate the effect of lithium on alleviating Akt1-related deficits. Taking advantage of Akt1+/- mice to mimic genetic deficiency in patients, behavioral impairments were replicated in female Akt1+/- mice but were alleviated by subchronic lithium treatment for 13 days. Lithium also effectively alleviated the observed reduction in phosphorylated GSK3α/ß expression in the brains of Akt1+/- mice. Furthermore, inhibition of Akt expression using an Akt1/2 inhibitor significantly reduced neurite length in P19 cells and primary hippocampal cell cultures, which was also ameliorated by lithium. Collectively, our findings implied the therapeutic potential of lithium and the importance of the AKT1-GSK3 signaling pathway.


Assuntos
Bases de Dados Factuais , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Seguro Saúde , Compostos de Lítio/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Transdução de Sinais , Adolescente , Adulto , Idoso , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Humanos , Compostos de Lítio/farmacologia , Masculino , Camundongos , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Taiwan , Adulto Jovem
12.
Environ Technol ; : 1-18, 2020 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-31973676

RESUMO

In this study, the three biofilm-anoxic-oxic-MBR systems were operated in parallel using different carbon source feed types. The three systems were operated with complete sludge retention to compare microbial community composition and system efficiency. High average removal of ammonia and COD was obtained in the three reactors. However, total nitrogen and total phosphorus removal efficiency were significantly higher in the VFAs feed systems when compared with the glucose feed system. The highest and most stable BNR efficiency was observed when acetate was used as a carbon source. The qPCR analysis revealed that ammonium oxidizing bacteria, denitrifiers and total bacteria were all highest in the acetate feed system followed by the propionate feed system. Moreover, among all carbon source types, the PUS-biofilm could maintain a higher degree of abundance of total bacteria than the sludge biomass. Meanwhile, ammonium oxidizing bacteria and denitrifiers were enriched in the sludge biomass rather than in the PUS-biofilm. The results of illumina sequencing revealed that acetate followed by propionate were favourable to the growth of microorganisms that were associated with the BNR process, which was the main reason for the high efficiency of nutrient removal in the acetate and propionate feed systems.

13.
Food Funct ; 10(12): 7634-7644, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31728459

RESUMO

Chemotherapy is currently used to treat colorectal cancer (CRC), the most common cancer worldwide. However, chemotherapeutic drugs are limited by severe side effects or drug resistance. In this study, bioactive compound(s), a mixture of palmitic acid, stearic acid, and glyceryl 1,3-dipalmitate (PSG), in Lactobacillus paracasei subsp. paracasei NTU 101-fermented reconstituted skimmed milk ethanol extract (NTU 101-FMEE) were isolated and identified. PSG (1 : 1.5 : 6.3) at 125 µg mL-1 could significantly decrease CRC cell viability at dosages that were not cytotoxic to healthy colon epithelial cells or macrophages. Moreover, the inhibitory effect of the combination of 62.5 µg mL-1 PSG (1 : 1.5 : 6.3) and 5-fluorouracil (5-FU) was significantly higher than that of 5-FU alone (p < 0.05). PSG up-regulated the activities of apoptosis-related proteins and down-regulated the nuclear factor-κB signaling pathway compared to the levels in the control group. Overall, PSG purified from NTU 101-FMEE possesses the potential to ameliorate CRC by improving the effects of adjuvant chemotherapy drugs and reducing side effects.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Produtos Fermentados do Leite/análise , Fluoruracila/farmacologia , Lactobacillus paracasei/metabolismo , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/fisiopatologia , Produtos Fermentados do Leite/microbiologia , Fermentação , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Ácido Palmítico/metabolismo , Ácido Palmítico/farmacologia , Ácidos Esteáricos/metabolismo , Ácidos Esteáricos/farmacologia
14.
Neuron ; 104(3): 471-487.e12, 2019 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-31606247

RESUMO

SETD1A, a lysine-methyltransferase, is a key schizophrenia susceptibility gene. Mice carrying a heterozygous loss-of-function mutation of the orthologous gene exhibit alterations in axonal branching and cortical synaptic dynamics accompanied by working memory deficits. We show that Setd1a binds both promoters and enhancers with a striking overlap between Setd1a and Mef2 on enhancers. Setd1a targets are highly expressed in pyramidal neurons and display a complex pattern of transcriptional up- and downregulations shaped by presumed opposing functions of Setd1a on promoters and Mef2-bound enhancers. Notably, evolutionarily conserved Setd1a targets are associated with neuropsychiatric genetic risk burden. Reinstating Setd1a expression in adulthood rescues cognitive deficits. Finally, we identify LSD1 as a major counteracting demethylase for Setd1a and show that its pharmacological antagonism results in a full rescue of the behavioral and morphological deficits in Setd1a-deficient mice. Our findings advance understanding of how SETD1A mutations predispose to schizophrenia (SCZ) and point to novel therapeutic interventions.


Assuntos
Córtex Cerebral/metabolismo , Disfunção Cognitiva/genética , Histona Desmetilases/metabolismo , Histona-Lisina N-Metiltransferase/genética , Memória de Curto Prazo , Esquizofrenia/genética , Psicologia do Esquizofrênico , Animais , Axônios/patologia , Encéfalo/metabolismo , Córtex Cerebral/patologia , Elementos Facilitadores Genéticos , Predisposição Genética para Doença , Histona Desmetilases/antagonistas & inibidores , Mutação com Perda de Função , Fatores de Transcrição MEF2/genética , Camundongos , Neocórtex/metabolismo , Neurônios/metabolismo , Fenótipo , Córtex Pré-Frontal/metabolismo , Regiões Promotoras Genéticas , Células Piramidais/metabolismo , Sinapses/patologia
15.
J Microbiol Immunol Infect ; 52(6): 902-910, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31607575

RESUMO

BACKGROUND: Acute respiratory tract infections are commonly caused by viruses in children. The differences in clinical data and outcome between single and multiple viral infections in hospitalized children were analyzed. METHODS: We retrospectively reviewed the medical records of hospitalized children who had fever and a xTAG Respiratory Virus Panel (RVP) test over a 2-year period. The clinical data were analyzed and compared between single and multiple viral infections. Viral etiologies in upper and lower respiratory infections were analyzed and compared. RESULTS: A total of 442 patients were enrolled. Patients with positive viral detection (N = 311) had a significantly lower rate of leukocytosis (p = 0.03), less evidence of bacterial infection (p = 0.004), and shorter duration of hospitalization (p = 0.019) than those with negative viral detection. The age of patients with multiple viral infections was younger than those with single viral infection; however, there were no significant differences in duration of fever, antibiotics treatment and hospitalization between these two groups. The most commonly identified virus was human rhinovirus. About 27% (n = 83) of patients had multiple viral infections. Overall, the highest percentage of human bocavirus infection was detected in multiple viral infections (79%). Lower respiratory tract infection (LRTI) was independently associated with multiple viral infections (p = 0.022), respiratory syncytial virus (RSV) infection (p = 0.001) and longer hospitalization duration (p = 0.011). CONCLUSION: Multiple viral infections were associated with younger age and a higher risk of developing LRTI. However, multiple viral infections did not predict a worse disease outcome. More studies are needed to unveil the interplay between the hosts and different viruses in multiple viral infections.


Assuntos
Coinfecção/virologia , Hospitalização/estatística & dados numéricos , Infecções Respiratórias/virologia , Viroses/diagnóstico , Criança , Pré-Escolar , Coinfecção/diagnóstico , Registros Eletrônicos de Saúde , Feminino , Febre/virologia , Humanos , Lactente , Masculino , Infecções Respiratórias/diagnóstico , Estudos Retrospectivos , Vírus/isolamento & purificação
16.
Sci Rep ; 9(1): 10459, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-31320679

RESUMO

The treatment of pediatric myocarditis is controversial, and the benefits of intravenous immunoglobulin (IVIG) are inconclusive due to limited data. We searched studies from PubMed, MEDLINE, Embase, and Cochrane Library databases since establishment until October 1st, 2018. Thirteen studies met the inclusion criteria. We included a total of 812 patients with IVIG treatment and 592 patients without IVIG treatment. The meta-analysis showed that the survival rate in the IVIG group was higher than that in the non-IVIG group (odds ratio = 2.133, 95% confidence interval (CI): 1.32-3.43, p = 0.002). There was moderate statistical heterogeneity among the included studies (I2 = 35%, p = 0.102). However, after adjustment using Duval and Tweedie's trim and fill method, the point estimate of the overall effect size was 1.40 (95% CI 0.83, 2.35), which became insignificant. Moreover, the meta-regression revealed that age (coefficient = -0.191, 95% CI (-0.398, 0.015), p = 0.069) and gender (coefficient = 0.347, 95% CI (-7.586, 8.279), p = 0.93) were not significantly related to the survival rate. This meta-analysis showed that IVIG treatment was not associated with better survival. The use of IVIG therapy in acute myocarditis in children cannot be routinely recommended based on current evidence. Further prospective and randomized controlled studies are needed to elucidate the effects of IVIG treatment.


Assuntos
Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Doenças do Recém-Nascido/tratamento farmacológico , Miocardite/tratamento farmacológico , Doença Aguda , Criança , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/patologia , Miocardite/patologia , Prognóstico
17.
J Clin Med ; 8(6)2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31167519

RESUMO

Exosome-mediated communication within the cardiac microenvironment is associated with cardiac fibrosis. Simvastatin (SIM), a potent statin, protects against cardiac fibrosis, but its mechanism of action is unclear. We investigated the inhibitory effects and underlying mechanism of simvastatin in cardiac fibrosis, by regulating exosome-mediated communication. Male Sprague-Dawley rats were treated with angiotensin (Ang) II alone, or with SIM for 28 d. Cardiac fibrosis, expressions of fibrosis-associated proteins and mRNAs, and collagen fiber arrangement and deposition were examined. Protein expressions in exosomes isolated from Ang II-treated cardiomyocytes (CMs) were evaluated using nano-ultra-performance liquid chromatographic system, combined with tandem mass spectrometry. Transformation of fibroblasts to myofibroblasts was evaluated using scanning electron and confocal microscopy, and migration assays. Our results showed that SIM attenuated in vivo expression of collagen and collagen-associated protein, as well as collagen deposition, and cardiac fibrosis. The statin also upregulated decorin and downregulated periostin in CM-derived exosomes. Furthermore, it suppressed Ang II-induced transformation of fibroblast to myofibroblast, as well as fibroblast migration. Exosome-mediated cell-cell communication within the cardiac tissue critically regulated cardiac fibrosis. Specifically, SIM regulated the release of CM exosomes, and attenuated Ang II-induced cardiac fibrosis, highlighting its potential as a novel therapy for cardiac fibrosis.

18.
Cardiovasc Diabetol ; 18(1): 45, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30935417

RESUMO

BACKGROUND: Sodium glucose co-transporter 2 inhibitor (SGLT2i), a new class of anti-diabetic drugs acting on inhibiting glucose resorption by kidneys, is shown beneficial in reduction of heart failure hospitalization and cardiovascular mortality. The mechanisms remain unclear. We hypothesized that SGLT2i, empagliflozin can improve cardiac hemodynamics in non-diabetic hypertensive heart failure. METHODS AND RESULTS: The hypertensive heart failure model had been created by feeding spontaneous hypertensive rats (SHR) with high fat diet for 32 weeks (total n = 13). Half SHRs were randomized to be administered with SGLT2i, empagliflozin at 20 mg/kg/day for 12 weeks. After evaluation of electrocardiography and echocardiography, invasive hemodynamic study was performed and followed by blood sample collection and tissue analyses. Empagliflozin exhibited cardiac (improved atrial and ventricular remodeling) and renal protection, while plasma glucose level was not affected. Empagliflozin normalized both end-systolic and end-diastolic volume in SHR, in parallel with parameters in echocardiographic evaluation. Empagliflozin also normalized systolic dysfunction, in terms of the reduced maximal velocity of pressure incline and the slope of end-systolic pressure volume relationship in SHR. In histological analysis, empagliflozin significantly attenuated cardiac fibrosis in both atrial and ventricular tissues. The upregulation of atrial and ventricular expression of PPARα, ACADM, natriuretic peptides (NPPA and NPPB), and TNF-α in SHR, was all restored by treatment of empagliflozin. CONCLUSIONS: Empagliflozin improves hemodynamics in our hypertensive heart failure rat model, associated with renal protection, attenuated cardiac fibrosis, and normalization of HF genes. Our results contribute some understanding of the pleiotropic effects of empagliflozin on improving heart function.


Assuntos
Compostos Benzidrílicos/farmacologia , Glucosídeos/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Hemodinâmica/efeitos dos fármacos , Hipertensão/complicações , Miocárdio/patologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Função do Átrio Esquerdo/efeitos dos fármacos , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Fibrose , Regulação da Expressão Gênica , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Hipertensão/fisiopatologia , Masculino , Miocárdio/metabolismo , Peptídeo Natriurético Encefálico/genética , Peptídeo Natriurético Encefálico/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Recuperação de Função Fisiológica , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
19.
Environ Sci Pollut Res Int ; 26(7): 6818-6828, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30635877

RESUMO

The harbor sediment containing high concentration of heavy metals may pose serious impacts on the marine ecosystem and environmental quality. The bioleaching process has been considered as an environmentally friendly and cost-effective alternative for removing heavy metals from contaminated sediments. In this study, a series of experiments were performed to investigate the feasibility of bioleaching process for removing heavy metals from the contaminated harbor sediments. The performance of the bioleaching process inoculated with sulfur-oxidizing microflora acclimated from the native harbor sediment was compared with that acclimated from the exogenous soil. In the bioleaching experiment with inoculants from native sediment, the efficiency of Zn, Cu, Cr, Pb, and Ni (30 days) reached 39-100%, 21-94%, 8-63%, 5-74%, and 19-77%, respectively. While 59-100% of Zn, 22-100% of Cu, 0-95% of Cr, 0-100% of Pb, and 22-100% of Ni were respectively removed in the bioleaching experiment with inoculants from exogenous soil after 30 days of reaction time. The results show that the rate and efficiency of metal removal in the bioleaching process decreased with an increase of sediment solid content from 10 to 40 g/L. The efficiency of metal removal in the bioleaching process with inoculants from the native sediment was lower than those from the exogenous soil due to the bacterial activity. By the fractionation of metal in the harbor sediment, exchangeable, carbonate-bound, and Fe/Mn oxide-bound metals (mobile fractions) were found to be apparently reduced and even organic matter/sulfide-bound and residual metals (stable fractions) were slightly removed after the bioleaching experiment.


Assuntos
Recuperação e Remediação Ambiental/métodos , Sedimentos Geológicos/microbiologia , Metais Pesados/análise , Poluentes Químicos da Água/análise , Bactérias , Microbioma Gastrointestinal , Sedimentos Geológicos/química , Metais Pesados/metabolismo , Solo , Enxofre , Poluentes Químicos da Água/metabolismo
20.
J Microbiol Immunol Infect ; 52(2): 352-362, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30177433

RESUMO

BACKGROUND/PURPOSE: The health risks of environmental heavy metals have been of concern are well known. The greater likelihood of heavy metal contamination in the physical environment increases the risk of asthma, especially in children. This cross-sectional, population-based study sought to investigate associations between heavy metal exposure and childhood asthma or wheezing. METHODS: Data from 5866 subjects, stratified into age groups of 2-5, 6-11, and 12-15 years, from the National Health and Nutrition Examination Survey 2007-2012 conducted by the Centers for Disease Control and Prevention were analyzed retrospectively. The primary outcome was active asthma. Variables included demographics, anthropometric, and clinical data. Univariate and multivariate logistic regression analyses were used to identify associations between blood heavy metal concentrations and adjusted odds (aORs) of active asthma. RESULTS: Higher concentration of blood lead was associated with higher adjusted odds of having asthma (aOR = 1.08, 95% CI = 1.00-1.16), but no significant effect was shown for current wheezing or whistling. Age-stratified analysis showed that higher blood lead concentration was associated with higher risk for active asthma (aOR = 1.24, 95% CI = 1.08-1.42) and current wheezing or whistling (aOR = 1.19, 95% CI = 1.04-1.38) in the 6-11 years age group, while higher blood mercury concentration was associated with lower risk of current wheezing or whistling (aOR = 0.95, 95% CI = 0.90-0.99). The medium concentration of blood lead was associated with decreased risks of current wheezing or whistling (aOR = 0.54, 95% CI = 0.30-0.96) in the 2-5 years age group. CONCLUSION: Higher concentrations of blood lead are associated with higher odds of asthma in children aged 2-15 years.


Assuntos
Asma/epidemiologia , Asma/etiologia , Exposição Ambiental/efeitos adversos , Metais Pesados/toxicidade , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Demografia , Poluição Ambiental , Feminino , Humanos , Masculino , Metais Pesados/sangue , Inquéritos Nutricionais , Sons Respiratórios/efeitos dos fármacos , Estudos Retrospectivos , Fatores de Risco , Fatores Socioeconômicos , Estados Unidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA