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1.
Technol Health Care ; 32(S1): 329-337, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38759059

RESUMO

BACKGROUND: Heart failure poses a significant challenge in the global health domain, and accurate prediction of mortality is crucial for devising effective treatment plans. In this study, we employed a Seq2Seq model from deep learning, integrating 12 patient features. By finely modeling continuous medical records, we successfully enhanced the accuracy of mortality prediction. OBJECTIVE: The objective of this research was to leverage the Seq2Seq model in conjunction with patient features for precise mortality prediction in heart failure cases, surpassing the performance of traditional machine learning methods. METHODS: The study utilized a Seq2Seq model in deep learning, incorporating 12 patient features, to intricately model continuous medical records. The experimental design aimed to compare the performance of Seq2Seq with traditional machine learning methods in predicting mortality rates. RESULTS: The experimental results demonstrated that the Seq2Seq model outperformed conventional machine learning methods in terms of predictive accuracy. Feature importance analysis provided critical patient risk factors, offering robust support for formulating personalized treatment plans. CONCLUSIONS: This research sheds light on the significant applications of deep learning, specifically the Seq2Seq model, in enhancing the precision of mortality prediction in heart failure cases. The findings present a valuable direction for the application of deep learning in the medical field and provide crucial insights for future research and clinical practices.


Assuntos
Aprendizado Profundo , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/mortalidade , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Taxa de Sobrevida , Fatores de Risco , Aprendizado de Máquina
2.
Talanta ; 276: 126301, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38781915

RESUMO

Large-area two-dimensional (2D) materials possess significant potential in the development of next generation semiconductor due to their unique physicochemical properties. Confocal Raman spectroscopy (CRM), a typical 2D material characterization method, has a limited effective measurement area owing to the restricted focus depth of the system and the less-than-ideal level of the substrate. We propose fast adaptive focusing confocal Raman microscopy (FAFCRM) to realize real-time focusing detection for large-area 2D materials. By observing spot changes on the charge coupled device (CCD) caused by placing an aperture in front of the CCD, the methodology gives a focusing resolution up to 100 nm per 60 µm without axial scanning. A graphene was measured over 25.6 mm × 25.6 mm area on focus through all the scanning. The research results provide new perspectives for non-destructive characterization of 2D materials at the inch level.

3.
Clin Cardiol ; 47(4): e24270, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628050

RESUMO

BACKGROUND: Earlier studies showed a negative correlation between life's simple 7 (LS7) and high-sensitivity C-reactive protein (hs-CRP), but no association has been found between life's essential 8 (LE8), an improved version of LS7, and hs-CRP. HYPOTHESIS: This study investigated the association between LE8 and hs-CRP utilizing data from the National Health and Nutritional Examination Survey. METHODS: A total of 7229 adults were incorporated in our study. LE8 was scored according to American Heart Association guidelines, and LE8 was divided into health behaviors and health factors. Serum samples of the participants were used to measure hs-CRP. To investigate the association between LE8 and hs-CRP, weighted linear regression, and restricted cubic spline were utilized. RESULTS: Among 7229 participants, the average age was 48.03 ± 16.88 years, 3689 (51.2%) were females and the median hs-CRP was 1.92 (0.81-4.49) mg/L. In adjusted weighted linear regression, a negative correlation was observed between the LE8 score and hs-CRP. Compared with the low LE8 score, the moderate LE8 score ß was -0.533 (-0.646 to -0.420), and the high LE8 score ß was -1.237 (-1.376 to -1.097). Health behaviors and health factors were also negatively associated with hs-CRP. In stratified analyses, the negative correlation between LE8 and hs-CRP remained consistent across subgroups. CONCLUSION: There was a negative correlation between LE8 as well as its sub-indicator scores and hs-CRP. Maintaining a positive LE8 score may be conducive to lowering the level of hs-CRP.


Assuntos
Proteína C-Reativa , Doenças Cardiovasculares , Estados Unidos/epidemiologia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Estudos Transversais , Inquéritos Nutricionais , American Heart Association , Modelos Lineares , Fatores de Risco
4.
Clin Cardiol ; 47(1): e24165, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37795956

RESUMO

OBJECTIVE: Sex difference is commonly observed in hypertension. We aimed to assess sex differences in the associations of modifiable lifestyle and metabolic risk factors with risk of hypertension. DESIGN: National cross-sectional population study. SETTING: Data from the 2007 to 2018 National Health and Nutrition Examination Survey. PARTICIPANTS: 7087 adults aged ≥30 years without a prior history of hypertension. PRIMARY AND SECONDARY OUTCOME MEASURES: Odds ratios and population attributable fraction (PAF) of hypertension associated with 10 modifiable risk factors: five lifestyle risk factors (current smoking, excess alcohol intake, poor diet, physical inactivity, and unhealthy sleep), and five metabolic risk factors (obesity, diabetes, dyslipidaemia, hyperuricemia, and chronic kidney disease) in women versus men. RESULTS: Compared with women, men had 84% increased risk of prevalence of hypertension. The sex difference in risk for hypertension is more evident in those aged <60 years (p for interaction <.001). For those aged <60 years the combination of lifestyle risk factors accounted for a PAF of 27.2% in men and 48.8% in women, and the combination of metabolic risk factors accounted for a PAF similarly in men (37.4%) and women (38.2%). For those aged ≥60 years, the PAF of lifestyle risk factors was similar between men and women and the metabolic risk factors accounted for a greater proportion in women (33.0% vs. 14.5% in men). CONCLUSIONS: Sex differences may exist in the relation and attribution of lifestyle and metabolic risk factors to hypertension, which may have implications for implementing sex-specific strategies to prevent hypertension.


Assuntos
Diabetes Mellitus , Hipertensão , Adulto , Feminino , Humanos , Masculino , Estudos Transversais , Inquéritos Nutricionais , Fatores de Risco , Hipertensão/epidemiologia , Hipertensão/complicações , Diabetes Mellitus/epidemiologia , Prevalência
5.
Cell Rep ; 42(8): 112915, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37537842

RESUMO

The nucleolus is the most prominent membraneless organelle within the nucleus. How the nucleolar structure is regulated is poorly understood. Here, we identified two types of nucleoli in C. elegans. Type I nucleoli are spherical and do not have visible nucleolar vacuoles (NoVs), and rRNA transcription and processing factors are evenly distributed throughout the nucleolus. Type II nucleoli contain vacuoles, and rRNA transcription and processing factors exclusively accumulate in the periphery rim. The NoV contains nucleoplasmic proteins and is capable of exchanging contents with the nucleoplasm. The high-order structure of the nucleolus is dynamically regulated in C. elegans. Faithful rRNA processing is important to prohibit NoVs. The depletion of 27SA2 rRNA processing factors resulted in NoV formation. The inhibition of RNA polymerase I (RNAPI) transcription and depletion of two conserved nucleolar factors, nucleolin and fibrillarin, prohibits the formation of NoVs. This finding provides a mechanism to coordinate structure maintenance and gene expression.


Assuntos
Caenorhabditis elegans , Proteínas Nucleares , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas Nucleares/metabolismo , Vacúolos/metabolismo , Nucléolo Celular/metabolismo , Núcleo Celular/metabolismo , RNA Ribossômico/metabolismo
6.
Plant Phenomics ; 5: 0082, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37602194

RESUMO

Quantifying canopy light interception provides insight into the effects of plant spacing, canopy structure, and leaf orientation on radiation distribution. This is essential for increasing crop yield and improving product quality. Canopy light interception can be quantified using 3-dimensional (3D) plant models and optical simulations. However, virtual 3D canopy models (VCMs) have often been used to quantify canopy light interception because realistic 3D canopy models (RCMs) are difficult to obtain in the field. This study aims to compare the differences in light interception between VCMs and RCM. A realistic 3D maize canopy model (RCM) was reconstructed over a large area of the field using an advanced unmanned aerial vehicle cross-circling oblique (CCO) route and the structure from motion-multi-view stereo method. Three types of VCMs (VCM-1, VCM-4, and VCM-8) were then created by replicating 1, 4, and 8 individual realistic plants constructed by CCO in the center of the corresponding RCM. The daily light interception per unit area (DLI), as computed for the 3 VCMs, exhibited marked deviation from the RCM, as evinced by the relative root mean square error (rRMSE) values of 20.22%, 17.38%, and 15.48%, respectively. Although this difference decreased as the number of plants used to replicate the virtual canopy increased, rRMSE of DLI for VCM-8 and RCM still reached 15.48%. It was also found that the difference in light interception between RCMs and VCMs was substantially smaller in the early stage (48 days after sowing [DAS]) than in the late stage (70 DAS). This study highlights the importance of using RCM when calculating light interception in the field, especially in the later growth stages of plants.

7.
PLoS Genet ; 19(2): e1010628, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36763670

RESUMO

Temperature greatly affects numerous biological processes in all organisms. How multicellular organisms respond to and are impacted by hypothermic stress remains elusive. Here, we found that cold-warm stimuli induced depletion of the RNA exosome complex in the nucleoli but enriched it in the nucleoplasm. To further understand the function and mechanism of cold-warm stimuli, we conducted forward genetic screening and identified ZTF-7, which is required for RNA exosome depletion from nucleoli upon transient cold-warm exposure in C. elegans. ZTF-7 is a putative ortholog of human ZNF277 that may contribute to language impairments. Immunoprecipitation followed by mass spectrometry (IP-MS) found that ZTF-7 interacted with RPS-2, which is a ribosomal protein of the small subunit and participates in pre-rRNA processing. A partial depletion of RPS-2 and other proteins of the small ribosomal subunit blocked the cold-warm stimuli-induced reduction of exosome subunits from the nucleoli. These results established a novel mechanism by which C. elegans responds to environmental cold-warm exposure.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Humanos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Núcleo Celular/metabolismo , Temperatura Baixa , Temperatura , Ligação Proteica
8.
Opt Express ; 30(23): 41447-41458, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36366623

RESUMO

Confocal Raman microscopy (CRM) has found applications in many fields as a consequence of being able to measure molecular fingerprints and characterize samples without the need to employ labelling methods. However, limited spatial resolution has limited its application when identification of sub-micron features in materials is important. Here, we propose a differential correlation-confocal Raman microscopy (DCCRM) method to address this. This new method is based on the correlation product method of Raman scattering intensities acquired when the confocal Raman pinhole is placed at different (defocused) positions either side of the focal plane of the Raman collection lens. By using this correlation product, a significant enhancement in the spatial resolution of Raman mapping can be obtained. Compared with conventional CRM, these are 23.1% and 33.1% in the lateral and axial directions, respectively. We illustrate these improvements using in situ topographic imaging and Raman mapping of graphene, carbon nanotube, and silicon carbide samples. This work can potentially contribute to a better understanding of complex nanostructures in non-real time spectroscopic imaging fields.

9.
Front Plant Sci ; 13: 966596, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082293

RESUMO

The non-uniform growth and development of crops within Chinese Solar Greenhouses (CSG) is directly related to the micro-light climate within canopy. In practice, reflective films are used to improve micro-light climate within plant canopy by homogenizing light distribution and so increasing total plant light interception. However, as to our knowledge, the contributions to light distribution within canopy have not been investigated for passive reflector like reflective films. Field experiments dealing with light conditions and growth behavior over time, are complicated to carry out, time-consuming and hard to control, while however, accurate measurements of how reflective films influence the micro-light climate of canopy are an essential step to improve the growth conditions for any crop. Here, we propose a supplementary light strategy using reflective films to improve light distribution within plant canopy. Based on the example of CSG, a 3D greenhouse model including a detailed 3D tomato canopy structure was constructed to simulate the influence of supplementary reflective films to improve micro-light climate. Comparison of measured solar radiation intensity with predicted model data demonstrated that the model could precisely predict light radiation intensity over time with different time points and positions in the greenhouse. A series of reflective film configurations were investigated based on features analysis of light distribution in the tomato canopy on sunny days using the proposed model. The reflective film configuration scheme with the highest impact significantly improved the evenness of horizontal and vertical light distribution in tomato canopy. The strategy provided here can be used to configure reflective films that will enhance light conditions in CSG, which can be applied and extended in different scenarios.

10.
Front Plant Sci ; 13: 828252, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242156

RESUMO

Determine the level of significance of planting strategy and plant architecture and how they affect plant physiology and dry matter accumulation within greenhouses is essential to actual greenhouse plant management and breeding. We thus analyzed four planting strategies (plant spacing, furrow distance, row orientation, planting pattern) and eight different plant architectural traits (internode length, leaf azimuth angle, leaf elevation angle, leaf length, leaflet curve, leaflet elevation, leaflet number/area ratio, leaflet length/width ratio) with the same plant leaf area using a formerly developed functional-structural model for a Chinese Liaoshen-solar greenhouse and tomato plant, which used to simulate the plant physiology of light interception, temperature, stomatal conductance, photosynthesis, and dry matter. Our study led to the conclusion that the planting strategies have a more significant impact overall on plant radiation, temperature, photosynthesis, and dry matter compared to plant architecture changes. According to our findings, increasing the plant spacing will have the most significant impact to increase light interception. E-W orientation has better total light interception but yet weaker light uniformity. Changes in planting patterns have limited influence on the overall canopy physiology. Increasing the plant leaflet area by leaflet N/A ratio from what we could observe for a rose the total dry matter by 6.6%, which is significantly better than all the other plant architecture traits. An ideal tomato plant architecture which combined all the above optimal architectural traits was also designed to provide guidance on phenotypic traits selection of breeding process. The combined analysis approach described herein established the causal relationship between investigated traits, which could directly apply to provide management and breeding insights on other plant species with different solar greenhouse structures.

12.
Nucleic Acids Res ; 49(16): 9194-9210, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34365510

RESUMO

Eukaryotic cells express a wide variety of endogenous small regulatory RNAs that function in the nucleus. We previously found that erroneous rRNAs induce the generation of antisense ribosomal siRNAs (risiRNAs) which silence the expression of rRNAs via the nuclear RNAi defective (Nrde) pathway. To further understand the biological roles and mechanisms of this class of small regulatory RNAs, we conducted forward genetic screening to identify factors involved in risiRNA generation in Caenorhabditis elegans. We found that risiRNAs accumulated in the RNA exosome mutants. risiRNAs directed the association of NRDE proteins with pre-rRNAs and the silencing of pre-rRNAs. In the presence of risiRNAs, NRDE-2 accumulated in the nucleolus and colocalized with RNA polymerase I. risiRNAs inhibited the transcription elongation of RNA polymerase I by decreasing RNAP I occupancy downstream of the RNAi-targeted site. Meanwhile, exosomes mislocalized from the nucleolus to nucleoplasm in suppressor of siRNA (susi) mutants, in which erroneous rRNAs accumulated. These results established a novel model of rRNA surveillance by combining ribonuclease-mediated RNA degradation with small RNA-directed nucleolar RNAi system.


Assuntos
RNA Ribossômico/metabolismo , RNA Interferente Pequeno/metabolismo , Elongação da Transcrição Genética , Animais , Caenorhabditis elegans , Nucléolo Celular/metabolismo , RNA Polimerases Dirigidas por DNA/metabolismo , Exossomos/genética , Exossomos/metabolismo , Inativação Gênica , Mutação , RNA Ribossômico/genética , RNA Interferente Pequeno/genética
13.
Aging (Albany NY) ; 13(12): 16816-16833, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34182541

RESUMO

BACKGROUND: Subarachnoid hemorrhage (SAH) is a life-threatening disease worldwide, and effective pharmaceutical treatment is still lacking. Celastrol is a plant-derived triterpene which showed neuroprotective potential in several types of brain insults. This study aimed to investigate the effects of celastrol on early brain injury (EBI) after SAH. METHODS: A total of sixty-one male Sprague-Dawley rats were used in this study. Rat SAH endovascular perforation model was established to mimic the pathological changes of EBI after SAH. Multiple methods such as 3.0T MRI scanning, immunohistochemistry, western blotting and propidium iodide (PI) labeling were used to explore the therapeutic effects of celastrol on SAH. RESULTS: Celastrol treatment attenuated SAH-caused brain swelling, reduced T2 lesion volume and ventricular volume in MRI scanning, and improved overall neurological score. Albumin leakage and the degradation of tight junction proteins were also ameliorated after celastrol administration. Celastrol protected blood-brain bairrer integrity through inhibiting MMP-9 expression and anti-neuroinflammatory effects. Additionally, necroptosis-related proteins RIP3 and MLKL were down-regulated and PI-positive cells in the basal cortex were less in the celastrol-treated SAH group than that in untreated SAH group. CONCLUSIONS: Celastrol exhibits neuroprotective effects on EBI after SAH and deserves to be further investigated as an add-on pharmaceutical therapy.


Assuntos
Barreira Hematoencefálica/patologia , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/etiologia , Necroptose/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Triterpenos Pentacíclicos/uso terapêutico , Hemorragia Subaracnóidea/complicações , Albuminas/metabolismo , Animais , Barreira Hematoencefálica/diagnóstico por imagem , Barreira Hematoencefálica/efeitos dos fármacos , Edema Encefálico/complicações , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/tratamento farmacológico , Lesões Encefálicas/diagnóstico por imagem , Ventrículos Cerebrais/efeitos dos fármacos , Ventrículos Cerebrais/patologia , Regulação para Baixo/efeitos dos fármacos , Inflamação/patologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Fármacos Neuroprotetores/farmacologia , Tamanho do Órgão/efeitos dos fármacos , Triterpenos Pentacíclicos/farmacologia , Proteínas Quinases/metabolismo , Ratos Sprague-Dawley , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Transdução de Sinais/efeitos dos fármacos , Hemorragia Subaracnóidea/diagnóstico por imagem , Análise de Sobrevida , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Regulação para Cima/efeitos dos fármacos
14.
PLoS One ; 15(11): e0242002, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33156887

RESUMO

In order to further improve the utilization of solar energy in Chinese Solar Greenhouse (CSG), this paper systematically studied the effects of orientation and structure on solar radiation interception in CSG. A solar radiation model has been developed based on the previous research, which taking solar motion law, meteorological data, and optical properties of materials into consideration. The established model was used to optimize the orientation and structure of CSG. The analysis of structure considered two major structural parameters, which are the ridge height and the horizontal projection of the rear roof. Moreover, the widely used Liao-Shen type Chinese solar greenhouse (CSG-LS) has been taken as the prototype in the present research, and the measured data of the typical clear day was used for the model validation. The results showed that the ridge height has a remarkable influence on the solar energy captured by CSG-LS. Compared with the optimization of a single factor, the comprehensive optimization of orientation and structure can increase the solar radiation interception of the rear wall by 3.95%. Considering the limiting factor of heat storage-release capacity and the shading effect on the greenhouse structure, the optimal lighting construction of the CSG-LS (with a span of 9.0 m) was specified as 7~9° from south to west of azimuth angle, 4.5~4.7 m ridge height, and 1.4~1.6 m horizontal projection of the rear roof at 42°N latitude. The proposed solar radiation model can provide scientific guidance for the CSG-LS construction in different areas.


Assuntos
Agricultura/métodos , Povo Asiático , Temperatura Alta , Humanos , Energia Solar , Luz Solar
15.
Orphanet J Rare Dis ; 15(1): 153, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546179

RESUMO

BACKGROUND: Extra-pelvic intravenous leiomyomatosis (IVL) extending into inferior vena cava (IVC) or heart (i.e. intracardiac leiomyomatosis, ICL) is an extremely rare benign disease. No consensus has been reached on the optimal surgical strategy. The aim of this study is to introduce four types of one-stage surgical strategies including less invasive options and a guideline to select patient-specific strategy for this disease. METHODS: Twenty-four patients of extra-pelvic IVLs receiving one-stage resections at the Zhongshan Hospital from July 2011 to November 2019 were reviewed retrospectively. Base on the initial experiences of the indiscriminate choices of tumor thrombectomies through sterno-laparotomy under cardiopulmonary bypass (CPB) in 6 ICLs, an anatomy-based guideline for four types of surgical strategies was developed and applied for the next 18 patients. RESULTS: Under the direction of guideline, tumor thrombectomies through single laparotomy were applied without CPB in 2 ICLs and 4 IVLs confined in IVC, or with CPB in 7 ICLs. Guideline-directed double-incisions with CPB were applied in only 5 ICLs, including 1 receiving mini-thoracotomy and 4 receiving sternotomy because of tumor adherences with right atriums in 2 and with pulmonary arteries in 2. All 24 patients accomplished one-stage panhysterectomy, bilateral adnexectomy and complete resections of intracaval and intracardiac tumors. For residual pelvic intravenous tumors in 19 patients, 17 received macroscopically complete resections while the other 2 failed because of high risk of hemorrhage. Intraoperative blood losses, operation time and hospitalization expense in the single-laparotomy non-CPB group were significantly lesser than the other groups. In CPB groups, inpatient stay and hospitalization expense in the single-incision group were significantly lesser than the double-incisions group. All patients were alive and free of recurrences during a mean follow-up of 35.4 ± 27.2 months (range, 1-100 months). The pelvic tumor residues in 2 patients remained unchanged for 51 and 52 months since operation, respectively. CONCLUSIONS: For various extra-pelvic IVLs, the 4 types of surgical strategies including less invasive options are feasible, providing these are selected by a guideline base on the tumor extension and morphology. The proposed guideline is believed to accommodate more patients receiving less invasive surgery without compromising the curative effect.


Assuntos
Neoplasias Cardíacas , Leiomiomatose , Neoplasias Cardíacas/cirurgia , Humanos , Leiomiomatose/cirurgia , Recidiva Local de Neoplasia , Estudos Retrospectivos , Veia Cava Inferior/cirurgia
16.
Cell Transplant ; 28(11): 1358-1372, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31370690

RESUMO

Despite the substantial efforts to elucidate the role of early brain injury in subarachnoid hemorrhage (SAH), an effective pharmaceutical therapy for patients with SAH continues to be unavailable. This study aims to reveal the role of necroptosis after SAH, and explore whether the disruption of the blood-brain barrier (BBB) and RIP3-mediated necroptosis following SAH in a rat SAH model are altered by necrostatin-1 via its selective inhibition of receptor-interacting protein kinase 1 (RIP1). Sixty-five rats were used in the experiments. The SAH model was established using endovascular perforation. Necrostatin-1 was intracerebroventricularly injected 1 h before SAH induction. The neuroprotective effects of necrostatin-1 were evaluated with multiple methods such as magnetic resonance imaging (MRI) scanning, immunohistochemistry, propidium iodide (PI) labeling, and western blotting. Pretreatment with necrostatin-1 attenuated brain swelling and reduced the lesion volume on T2 sequence and ventricular volume on MRI 72 h after SAH induction. Albumin leakage and the degradation of tight junction proteins were also ameliorated by necrostatin-1 administration. In addition, necrostatin-1 decreased the number of PI-positive cells in the basal cortex, reduced the levels of the RIP3 and MLKL proteins, and inhibited the production of the pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. Based on the findings from the present study, the selective RIP1 inhibitor necrostatin-1 functioned as a neuroprotective agent after SAH by attenuating brain swelling and BBB disruption. Moreover, the necrostatin-1 pretreatment prevented SAH-induced necroptosis by suppressing the activity of the RIP3/MLKL signaling pathway. These results will provide insights into new drugs and pharmacological targets to manage SAH, which are worth further study.


Assuntos
Barreira Hematoencefálica/metabolismo , Encéfalo/efeitos dos fármacos , Imidazóis/uso terapêutico , Indóis/uso terapêutico , Necroptose/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Hemorragia Subaracnóidea/tratamento farmacológico , Animais , Encéfalo/citologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Edema Encefálico/tratamento farmacológico , Citocinas/metabolismo , Imageamento por Ressonância Magnética , Metaloproteinase 9 da Matriz/metabolismo , Necroptose/genética , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Hemorragia Subaracnóidea/metabolismo , Hemorragia Subaracnóidea/mortalidade , Hemorragia Subaracnóidea/patologia , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/patologia
17.
BMJ Open ; 9(7): e028211, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350245

RESUMO

OBJECTIVE: Ceramides are associated with coronary plaque vulnerability. We aim to investigate the potential diagnostic value of ceramides for acute coronary syndrome (ACS) in Chinese patients with chest pain. DESIGN: Prospective observational survey. SETTING: Shanghai, China, 2016-2017. PARTICIPANTS: A total of 2773 patients with chest pain from four hospitals in Shanghai, China, between August 2016 and October 2017. MAIN OUTCOME MEASURES: Performance of metabolites model in detection of ACS cases including ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and unstable angina. RESULTS: Plasma levels of 12 ceramide molecules and corresponding ratios were compared between patients diagnosed with ACS and those without. Cer(d18:1/24:1(15Z))/Cer(d18:1/24:0) ratio, Cer(d18:1/14:0) and Cer(d18:1/22:0) were independent predictors of ACS after adjustment of traditional risk factors and high-sensitivecardiac troponin T. Receiver operating characteristic curve analysis showed a significant improvement in detecting ACS in the multivariable model with ceramides compared with that without (0.865 (0.840 to 0.889) vs 0.808 (0.776 to 0.841), p<0.001). CONCLUSION: Distinct plasma ceramides are independent diagnostic predictors of ACS among patients with chest pain. Ceramides together with high-sensitive troponin and traditional factors showed great potential in identifying ACS among patients with chest pain.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Ceramidas/sangue , Dor no Peito/diagnóstico , Troponina T/sangue , Síndrome Coronariana Aguda/sangue , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade
18.
Cell Rep ; 27(12): 3561-3572.e3, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216475

RESUMO

piRNAs play significant roles in suppressing transposons and nonself nucleic acids, maintaining genome integrity, and defending against viral infections. In C. elegans, piRNA precursors are transcribed in the nucleus and are subjected to a number of processing and maturation steps. The biogenesis of piRNAs is not fully understood. We use functional proteomics in C. elegans and identify a piRNA biogenesis and chromosome segregation (PICS) complex. The PICS complex contains TOFU-6, PID-1, PICS-1, TOST-1, and ERH-2, which exhibit dynamic localization among different subcellular compartments. In the germlines, the PICS complex contains TOFU-6/PICS-1/ERH-2/PID-1, is largely concentrated at the perinuclear granule zone, and engages in piRNA processing. During embryogenesis, the TOFU-6/PICS-1/ERH-2/TOST-1 complex accumulates in the nucleus and plays essential roles in chromosome segregation. The functions of these factors in mediating chromosome segregation are independent of piRNA production. We speculate that differential compositions of PICS factors may help cells coordinate distinct cellular processes.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Segregação de Cromossomos , Regulação da Expressão Gênica , Proteoma/análise , RNA Interferente Pequeno/biossíntese , RNA Interferente Pequeno/genética , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Proteínas de Caenorhabditis elegans/genética , Embrião não Mamífero/citologia , Embrião não Mamífero/metabolismo , Células Germinativas/citologia , Células Germinativas/metabolismo
19.
Nano Lett ; 19(2): 829-838, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30605619

RESUMO

Spinal cord injury (SCI) routinely causes the immediate loss and disruption of neurons followed by complicated secondary injuries, including inflammation, oxidative stress, and dense glial scar formation. Inhibitory factors in the lesion scar and poor intrinsic neural regeneration capacity restrict functional recovery after injury. Minocycline, which has neuroprotective activity, can alleviate secondary injury, but the long-term administration of this drug may cause toxicity. Polysialic acid (PSA) is a large cell-surface carbohydrate that is critical for central nervous system development and is capable of promoting precursor cell migration, axon path finding, and synaptic remodeling; thus, PSA plays a vital role in tissue repair and regeneration. Here, we developed a PSA-based minocycline-loaded nanodrug delivery system (PSM) for the synergistic therapy of spinal cord injury. The prepared PSM exerted marked anti-inflammatory and neuroprotective activities both in vitro and in vivo. The administration of PSM could significantly protect neurons and myelin sheaths from damage, reduce the formation of glial scar, recruit endogenous neural stem cells to the lesion site, and promote the regeneration of neurons and the extension of long axons throughout the glial scar, thereby largely improving the locomotor function of SCI rats and exerting a superior therapeutic effect. The findings might provide a novel strategy for SCI synergistic therapy and the utilization of PSA in other central nervous system diseases.


Assuntos
Antibacterianos/uso terapêutico , Portadores de Fármacos/uso terapêutico , Minociclina/uso terapêutico , Regeneração Nervosa/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Ácidos Siálicos/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Micelas , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ratos , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia
20.
Eur J Vasc Endovasc Surg ; 57(3): 434-441, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30087010

RESUMO

OBJECTIVES: Acute aortic dissection (AAD) is a severe clinical emergency with a high mortality, and is easily misdiagnosed in its early stage. This study aimed at discovering serum metabolomic markers with the potential to diagnose AAD and distinguish between two subtypes of AAD. METHODS: Thirty-five patients with AAD, including 20 with Stanford type A and 15 with Stanford type B were enrolled in this study, together with 20 healthy controls. All patients with AAD were admitted within 72 h of onset. Serum metabolomics profiles were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and the data were analysed by principal component analysis and partial least squares discriminant analysis. RESULTS: A total of 17 metabolites differing between the control and AAD groups were finally screened and identified as lysophosphatidylcholines (LPC) and sphingolipids including sphinganine, phytosphingosine, sphingomyelin, and ceramide. Compared with those in the healthy control group, LPC levels were significantly lower in both the Stanford type A and type B AAD groups. Interestingly, sphingolipids, including sphinganine, phytosphingosine, and ceramide, were remarkably reduced in the Stanford type A AAD group, but not in the Stanford type B AAD group. Subgroup analysis showed that the changes in LPC and sphingolipid levels were unrelated to hypertension or gender. CONCLUSIONS: The present results indicate that LPCs and sphingolipids are significantly altered in patients with AAD, and several sphingolipids, such as sphinganine, phytosphingosine, and ceramide, were dramatically decreased in patients with Stanford type A AAD. A combination of these two families of metabolites could serve as a potential biomarker for the diagnosis of AAD and distinguishing between Stanford type A and Stanford type B.


Assuntos
Aneurisma Aórtico/sangue , Aneurisma Aórtico/diagnóstico , Dissecção Aórtica/sangue , Dissecção Aórtica/diagnóstico , Lisofosfatidilcolinas/sangue , Metabolômica/métodos , Esfingolipídeos/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Cromatografia Líquida , Diagnóstico Diferencial , Análise Discriminante , Feminino , Humanos , Análise dos Mínimos Quadrados , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Análise de Componente Principal
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