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2.
Environ Sci Process Impacts ; 26(7): 1156-1170, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38812434

RESUMO

One major challenge in predicting secondary organic aerosol (SOA) formation in the atmosphere is incomplete representation of biogenic volatile organic compounds (BVOCs) emitted from plants, particularly those that are emitted as a result of stress - a condition that is becoming more frequent in a rapidly changing climate. One of the most common types of BVOCs emitted by plants in response to environmental stress are acyclic terpenes. In this work, SOA is generated from the photooxidation of acyclic terpenes in an oxidation flow reactor and compared to SOA production from a reference cyclic terpene - α-pinene. The acyclic terpenes used as SOA precursors included ß-myrcene, ß-ocimene, and linalool. Results showed that oxidation of all acyclic terpenes had lower SOA yields measured after 4 days photochemical age, in comparison to α-pinene. However, there was also evidence that the condensed organic products that formed, while a smaller amount overall, had a higher oligomeric content. In particular, ß-ocimene SOA had higher oligomeric content than all the other chemical systems studied. SOA composition data from ultra-high performance liquid chromatography with electrospray ionization mass spectrometry (UHPLC-ESI-MS) was combined with mechanistic modeling using the Generator for Explicit Chemistry and Kinetics of Organics in the Atmosphere (GECKO-A) to explore chemical mechanisms that could lead to this oligomer formation. Calculations based on composition data suggested that ß-ocimene SOA was more viscous with a higher glass transition temperature than other SOA generated from acyclic terpene oxidation. This was attributed to a higher oligomeric content compared to other SOA systems studied. These results contribute to novel chemical insights about SOA formation from acyclic terpenes and relevant chemistry processes, highlighting the importance of improving underrepresented biogenic SOA formation in chemical transport models.


Assuntos
Aerossóis , Poluentes Atmosféricos , Oxirredução , Terpenos , Compostos Orgânicos Voláteis , Aerossóis/química , Compostos Orgânicos Voláteis/química , Poluentes Atmosféricos/química , Poluentes Atmosféricos/análise , Terpenos/química , Monoterpenos Acíclicos/química , Modelos Químicos , Processos Fotoquímicos , Atmosfera/química , Monoterpenos Bicíclicos/química , Monoterpenos/química , Monitoramento Ambiental/métodos
3.
Environ Sci Technol Lett ; 11(2): 130-135, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38371653

RESUMO

Emissions from volatile chemical products (VCPs) have been identified as contributors to air quality degradation in urban areas. Limonene can be a tracer compound for VCPs containing fragrances in densely populated regions, but limonene is also emitted from conifers that are planted in urban areas. This creates challenges for using limonene to estimate VCP emissions. In this study, the -/+ enantiomeric ratios of limonene from VCP and conifer emission sources were quantified to evaluate if this measurement could be used to aid in source apportionment and emission inventory development. Samples were analyzed using a gas chromatograph equipped with a chiral column and mass spectrometry. The results demonstrate that limonene exhibits distinct enantiomeric ratios when sourced from VCPs versus conifers. (+)-Limonene was dominant in VCP sources (>97%), which was not universally true for conifer sources. The results were compared to those of air samples collected outside at two locations and indoors. The levels of (-)-limonene in outdoor air in Irvine and Portland and in indoor air were 50%, 22%, and 4%, respectively. This suggests outdoor limonene had both VCP and plant emission sources while indoor air was dominated by VCP sources. This study demonstrates the potential utility of enantiomeric analysis for improving VCP emission estimates in urban areas.

4.
Nat Prod Res ; 38(10): 1719-1726, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37265118

RESUMO

A new lignan, named pouzolignan P (1), together with 14 known ones (2 - 15) were isolated from the roots of Pouzolzia zeylanica (L.) Benn. Their structures were deduced based on the detailed spectroscopic analysis. All the isolates were evaluated for their inhibitory activities toward the ATP citrate lyase (ACLY). Among them, four lignans, isopouzolignan K (3), gnemontanins E (5), gnetuhainin I (6), and styraxlignolide D (15) showed excellent ACLY inhibitory effect with IC50 values of 9.06, 0.59, 2.63, and 7.62 µM, respectively. These compounds were further evaluated for their cholesterol-lowing effects on ox-LDL-induced high-cholesterol HepG2 cells. Compound 15 emerges as the most potent ACLY inhibitor, which significantly decreased the TC level in a dose-dependent manner. In addition, molecular docking simulations elucidated that 15 formed a strong hydrogen-bond interaction with Glu599 of ACLY, which was an important site responsible for the enzyme catalytic activity.


Assuntos
ATP Citrato (pro-S)-Liase , Lignanas , ATP Citrato (pro-S)-Liase/química , Simulação de Acoplamento Molecular , Inibidores Enzimáticos/farmacologia , Colesterol
5.
Hepatol Int ; 18(1): 4-31, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37864725

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Resultado do Tratamento , Artéria Hepática/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/uso terapêutico , Infusões Intra-Arteriais
6.
Med Phys ; 50(11): 6762-6778, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37675888

RESUMO

BACKGROUND: Flat panel detector (FPD) based cone-beam computed tomography (CT) has made tremendous progress in the last two decades, with many new and advanced medical and industrial applications keeping emerging from diagnostic imaging and image guidance for radiotherapy and interventional surgery. The current cone-beam CT (CBCT), however, is still suboptimal for head CT scan which requires a high standard of image quality. While the dual-layer FPD technology is under extensive development and is promising to further advance CBCT from qualitative anatomic imaging to quantitative dual-energy CT, its potential of enabling head CBCT applications has not yet been fully investigated. PURPOSE: The relatively moderate energy separation from the dual-layer FPD and the overall low signal level especially at the bottom-layer detector, could raise significant challenges in performing high-quality dual-energy material decomposition (MD). In this work, we propose a hybrid, physics and model guided, MD algorithm that attempts to fully use the detected x-ray signals and prior-knowledge behind head CBCT using dual-layer FPD. METHODS: Firstly, a regular projection-domain MD is performed as initial results of our approach and for comparison as conventional method. Secondly, based on the combined projection, a dual-layer multi-material spectral correction (dMMSC) is applied to generate beam hardening free images. Thirdly, the dMMSC corrected projections are adopted as a physics-model based guidance to generate a hybrid MD. A set of physics experiments including fan-beam scan and cone-beam scan using a head phantom and a Gammex Multi-Energy CT phantom are conducted to validate our proposed approach. RESULTS: The combined reconstruction could reduce noise by about 10% with no visible resolution degradation. The fan-beam studies on the Gammex phantom demonstrated an improved MD performance, with the averaged iodine quantification error for the 5-15 mg/ml iodine inserts reduced from about 5.6% to 3.0% by the hybrid method. On fan-beam scan of the head phantom, our proposed hybrid MD could significantly reduce the streak artifacts, with CT number nonuniformity (NU) in the selected regions of interest (ROIs) reduced from 23 Hounsfield Units (HU) to 4.2 HU, and the corresponding noise suppressed from 31 to 6.5 HU. For cone-beam scan, after scatter correction (SC) and cone-beam artifact reduction (CBAR), our approach can also significantly improve image quality, with CT number NU in the selected ROI reduced from 24.2 to 6.6 HU and the noise level suppressed from 22.1 to 8.2 HU. CONCLUSIONS: Our proposed physics and model guided hybrid MD for dual-layer FPD based head CBCT can significantly improve the robustness of MD and suppress the low-signal artifact. This preliminary feasibility study also demonstrated that the dual-layer FPD is promising to enable head CBCT spectral imaging.


Assuntos
Iodo , Tomografia Computadorizada por Raios X , Estudos de Viabilidade , Tomografia Computadorizada de Feixe Cônico/métodos , Cabeça/diagnóstico por imagem , Algoritmos , Imagens de Fantasmas , Artefatos , Processamento de Imagem Assistida por Computador/métodos
7.
Signal Transduct Target Ther ; 8(1): 58, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-36750721

RESUMO

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Estudos de Coortes , Neoplasias Hepáticas/patologia , Terapia de Alvo Molecular , Estudos Retrospectivos
8.
Artigo em Inglês | MEDLINE | ID: mdl-35805656

RESUMO

Carbon dioxide mainly comes from industrial economic activities. Industrial structure optimization is an effective way to reduce carbon dioxide emissions. This paper uses the panel data of 13 cities in the Beijing-Tianjin-Hebei urban agglomeration from 2006 to 2019, uses the Theil index to calculate the industrial structure rationalization index, and uses the proportion of industrial added value to calculate the industrial structure upgrade index. By constructing the STIRPAT model, this paper quantitatively analyzes the impact of industrial structure rationalization and upgrade on carbon emissions. The results show that the rationalization and upgrading of industrial structure in the Beijing-Tianjin-Hebei urban agglomeration significantly inhibit carbon emissions. Compared with the rationalization of the industrial structure, the upgrading of industrial structure in the Beijing-Tianjin-Hebei urban agglomeration has a better effect on carbon emission reduction. For the Beijing-Tianjin-Hebei urban agglomeration, government expenditure on science and technology can promote the upgrading of industrial structure to a certain extent, thereby reducing carbon emissions. There is a big gap between the industrial structure development level of Hebei province and that of Beijing and Tianjin. Finally, based on the conclusion, this paper puts forward the policy enlightenment of promoting the optimization process of industrial structure and reducing carbon emissions of the Beijing-Tianjin-Hebei urban agglomeration.

9.
J Org Chem ; 87(12): 8158-8169, 2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35675122

RESUMO

The additive-free [3 + 2] annulation from isatins, amino acids with 2-styrylbenzoxazoles, was described, providing a series of functional and structurally complex 3,3'-pyrrolidinyl-spirooxindole derivatives containing four contiguous and two quaternary stereogenic centers in high yields (up to 95%) and excellent diastereoselectivities (up to >25:1 dr). Interestingly, the reaction exhibits switchable regioselectivity depending on the substrate of amino acids. With proline or thioproline as the substrate, the reaction afforded α-regioselective spirooxindole skeletons. In contrast, when piperidine acid is the substrate, the reaction provided γ-regioselective spirooxindole skeletons.


Assuntos
Compostos de Espiro , Aminoácidos , Catálise , Indóis/química , Compostos de Espiro/química , Estereoisomerismo
10.
Front Aging Neurosci ; 14: 864128, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601623

RESUMO

Background: The evidence of the association between parity and risk of mild cognitive impairment (MCI) or dementia is mixed, and the relationship between parity and longitudinal cognitive changes is less clear. We investigated these issues in a large population of older women who were carefully monitored for development of MCI and probable dementia. Methods: Using the Women's Health Initiative Memory Study, 7,100 postmenopausal women (mean age 70.1 ± 3.8 years) with information on baseline parity (defined as the number of term pregnancies), measures of global cognition (Modified Mini-Mental State Examination score) from 1996-2007, and cognitive impairment (centrally adjudicated diagnoses of MCI and dementia) from 1996-2016 were included. Multivariable linear mixed-effects models were used to analyze the rate of changes in global cognition. Cox regression models were used to evaluate the risk of MCI/dementia across parity groups. Results: Over an average of 10.5 years, 465 new cases of MCI/dementia were identified. Compared with nulliparous women, those with a parity of 1-3 and ≥4 had a lower MCI/dementia risk. The HRs were 0.75 (0.56-0.99) and 0.71 (0.53-0.96), respectively (P < 0.01). Similarly, a parity of 1-3 and ≥4 was related to slower cognitive decline (ß = 0.164, 0.292, respectively, P < 0.05). Conclusion: Higher parity attenuated the future risk for MCI/dementia and slowed the rates of cognitive decline in elderly women. Future studies are needed to determine how parity affects late-life cognitive function in women.

11.
Environ Sci Technol ; 55(18): 12191-12201, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34495669

RESUMO

Assessing the role of volatile organic compounds (VOCs) in production of ozone and secondary organic aerosol (SOA) is especially important in light of ongoing policy goals. Here, we estimated the ozone formation potential (OFP) and SOA formation potential (SOAP) of anthropogenic and biogenic VOC emissions to evaluate (1) anthropogenic VOCs and associated sectors that dominate OFP and SOAP and (2) the potential impacts of enhanced biogenic VOCs from urban greening programs on air quality in Los Angeles county. In the present-day scenario, ethylene had the largest OFP followed by m & p-xylene, toluene, propylene, and formaldehyde. The top five contributors to SOAP were toluene, mineral spirits, benzene, heptadecane, and hexadecane. Mobile and solvent sources were the dominant VOC sources for both OFP and SOAP. The potential increases in biogenic VOC emissions due to future urban greening had significant effects on urban air quality that offset the benefits of reducing anthropogenic VOC emissions. This study demonstrates that urban greening programs in Los Angeles county, and likely other cities as well, need to account for both anthropogenic and biogenic VOC contributions to secondary pollution, and greening cities should consider using vegetation types with low VOC emissions to avoid further degradation to urban air quality.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Ozônio , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Los Angeles , Ozônio/análise , Compostos Orgânicos Voláteis/análise
12.
Pharmacology ; 106(9-10): 509-519, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34412054

RESUMO

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC), which is difficult to diagnose and is usually fatal due to its late clinical presentation and a lack of effective treatment, has risen over the past decades but without much improvement in prognosis. OBJECTIVE: The study aimed to investigate the role of apatinib that targets vascular endothelial growth factor receptor-2 (VEGFR2) in ICC. METHODS: MTT assays, cell scratch assays, and tube formation assays were used to assess the effect of apatinib on human ICC cell line (HuCCT-1) and RBE cells proliferation, migration, and angiogenic capacity, respectively. Expression of vascular endothelial growth factor (VEGF), VEGFR2, signal transducer and activator of transcription factor 3 (STAT3), pSTAT3, and hypoxia inducible factor 1 subunit alpha (HIF-1α) pathway proteins was assessed using Western blotting and mRNA expression analysis in HuCCT-1 was performed using RT-qPCR assays. The pcDNA 3.1(-)-VEGFR2 and pcDNA 3.1(-)-HIF-1α were transfected into HuCCT-1 and RBE cells using Lipofectamine 2,000 to obtain overexpressed HuCCT-1 and RBE cells. RESULTS: We found that apatinib-inhibited proliferation, migration, and angiogenesis of HuCCT-1 and RBE cells in vitro in a dose-dependent manner. We also proved that apatinib effectively inhibits angiogenesis in tumor cells by blocking the expression of VEGF and VEGFR2 in these cells. In addition, we demonstrated that apatinib regulates the expression of STAT3 phosphorylation by inhibiting VEGFR2. Finally, we showed that apatinib regulates ICC angiogenesis and HIF-1α/VEGF expression via STAT3. CONCLUSIONS: Based on the above findings, we conclude that apatinib inhibits HuCCT-1 and RBE cell proliferation, migration, and tumor angiogenesis by inhibiting the VEGFR2/STAT3/HIF-1α axis signaling pathway. Apatinib can be a promising drug for ICC-targeted molecular therapy.


Assuntos
Antineoplásicos/farmacologia , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Neovascularização Patológica/patologia , Piridinas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator 3 de Transcrição/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos
13.
Cytokine ; 143: 155488, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33814272

RESUMO

BACKGROUND: The inhibition of glucocorticoid (GC) on osteoblastic differentiation of bone marrow stromal stem cells (BMSC) is an important pathway for GC to reduce bone formation. Recent studies implicated an important role of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in GC-mediated cell proliferation and differentiation. Thus, our purpose is to investigate the role of PPAR-γ in regulating rat BMSC (rBMSC) osteoblastic differentiation. METHODS: The rBMSC treated with dexamethasone (Dex) was used to construct an in vitro cell model of GC-induced osteoporosis. The expressions of PPAR-γ, RUNX2, ALP, OPN and SFRP5 in cells were detected by RT-qPCR and western blot assays. Osteogenic differentiation of rBMSC was measured by Alizarin Red S (ARS) staining analysis. Lentivirus-delivered shRNA was used to knock down PPAR-γ or SFRP5, and lentivirus-delivered constructs were used to overexpress SFRP5 in rBMSC to verify the effect of PPAR-γ or SFRP5 on cell osteogenic differentiation. RESULTS: Dex significantly reduced rBMSC osteoblastic differentiation. The expression of PPAR-γ was enhanced in Dex treated rBMSC. PPAR-γ down-regulation improved Dex inhibition of rBMSC osteogenic differentiation. Moreover, PPAR-γ knockdown promoted protein levels of RUNX2, ALP, OPN and Dex-decreased rBMSC osteogenic differentiation. The expression of SFRP5 was reduced while Wnt and ß-catenin were increased in PPAR-γ knockdown and Dex treated rBMSC. Moreover, the up-regulation of SFRP5 reversed the osteogenic differentiation of rBMSC induced by PPAR-γ knockdown. CONCLUSION: These data indicated that in GC-induced osteoporosis, PPAR-γ/SFRP5 affects osteogenic differentiation by regulating the Wnt/ß-catenin signaling pathway.


Assuntos
Adipocinas/metabolismo , Dexametasona/efeitos adversos , Osteoporose/induzido quimicamente , Osteoporose/metabolismo , PPAR gama/metabolismo , Via de Sinalização Wnt , Adipocinas/genética , Animais , Diferenciação Celular , Feminino , Técnicas de Silenciamento de Genes , Células-Tronco Mesenquimais/metabolismo , Modelos Biológicos , Osteogênese , Ratos , Ratos Sprague-Dawley , Transcrição Gênica
14.
Integr Cancer Ther ; 20: 15347354211002919, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33834863

RESUMO

OBJECTIVE: To provide higher level evidence on the benefits of a Chinese patent medicine (CPM) (Fufang E'jiao Syrup, FFEJS) for alleviating cancer-related fatigue (CRF), this article describes a protocol for a randomized controlled trial. METHODS/DESIGN: We designed a double-blind, placebo-controlled stratified permuted block randomization clinical trial on CRF among 3 types of cancer in China. Participants will be equally allocated to FFEJS group or placebo group according to the randomization sequence and the hospitals they were enrolled at. Each patient will receive 20 ml of either the study formula FFEJS or a placebo formula, 3 times a day for 6 weeks. The follow-up period will be another 4 weeks for safety evaluation. The primary outcome is the difference in improvement of fatigue as measured with the Revised Piper Fatigue Scale-Chinese Version (RPFS-CV). Secondary outcomes include change in fatigue (measured by routine blood panel and hormones in peripheral blood) and QoL (measured by Edmonton symptom assessment scale and Functional Assessment of Cancer Therapy). Patient safety will be measured by liver, renal or cardiac damage, and the risk of FFEJS having a tumor promotion and progression effect will be monitored throughout this study. Cost-effectiveness will also be evaluated mainly by incremental cost per each quality-adjusted life year gained. DISCUSSION: This article describes the study design of a CPM for CRF in patients with advanced cancer through exploring the effectiveness, safety, and cost-effectiveness of FFEJS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04147312. Registered on 1 Sep 2019.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias , China , Análise Custo-Benefício , Método Duplo-Cego , Medicamentos de Ervas Chinesas/uso terapêutico , Fadiga/tratamento farmacológico , Fadiga/etiologia , Humanos , Estudos Multicêntricos como Assunto , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Medicamentos sem Prescrição , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
Neuron ; 108(1): 180-192.e5, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-32827455

RESUMO

During development, endothelial tip cells (ETCs) located at the leading edge of growing vascular plexus guide angiogenic sprouts to target vessels, and thus, ETC pathfinding is fundamental for vascular pattern formation in organs, including the brain. However, mechanisms of ETC pathfinding remain largely unknown. Here, we report that Piezo1-mediated Ca2+ activities at primary branches of ETCs regulate branch dynamics to accomplish ETC pathfinding during zebrafish brain vascular development. ETC branches display spontaneous local Ca2+ transients, and high- and low-frequency Ca2+ transients cause branch retraction through calpain and branch extension through nitric oxide synthase, respectively. These Ca2+ transients are mainly mediated by Ca2+-permeable Piezo1 channels, which can be activated by mechanical force, and mutating piezo1 largely impairs ETC pathfinding and brain vascular patterning. These findings reveal that Piezo1 and downstream Ca2+ signaling act as molecular bases for ETC pathfinding and highlight a novel function of Piezo1 and Ca2+ in vascular development.


Assuntos
Vasos Sanguíneos/crescimento & desenvolvimento , Encéfalo/irrigação sanguínea , Cálcio/metabolismo , Células Endoteliais/metabolismo , Canais Iônicos/genética , Neovascularização Fisiológica/genética , Proteínas de Peixe-Zebra/genética , Animais , Encéfalo/crescimento & desenvolvimento , Sinalização do Cálcio , Calpaína/metabolismo , Canais Iônicos/metabolismo , Mecanotransdução Celular , Mutação , Óxido Nítrico Sintase/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
16.
Med Sci Monit ; 26: e920849, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32332694

RESUMO

BACKGROUND Sevoflurane as a widely used inhalational general anesthetic that also has a cardioprotective role in hypoxia-reoxygenation (H/R) injury. This study aimed to investigate the effects of microRNA-107 (miR-107) on sevoflurane postconditioning (SpostC) in H9C2 embryonic rat cardiomyocytes and to use bioinformatics analysis to identify the molecular basis of cardioprotection from sevoflurane in human cardiac tissue. MATERIAL AND METHODS The STRADA gene was identified from the Gene Expression Omnibus (GEO) database. H9C2 embryonic rat cardiomyocytes were cultured with sevoflurane. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to measure the mRNA expression and protein expression of STRADA and miR-107 in H9C2 cells. TargetScanHuman version 7.2 was used to identify the target gene of miR-107 and to predict the STRADA 3'-UTR binding site of miR-107. The dual-luciferase reporter assay measured the relative luciferase activity. The cell proliferation rate and cell apoptosis were measured using the MTT assay and flow cytometry, respectively. RESULTS H/R injury in H9C2 cells following SpostC resulted in increased expression of miR-107 and reduced expression of STRADA. Specific binding of miR-107 was identified to STRADA 3'-UTR. Upregulation of the miR-107 in SpostC H/R injured H9C2 cells promoted cell proliferation, reduced cell apoptosis, and downregulating the protein expression of caspase-3. STRADA overexpression reduced the effects of a miR-107 mimic on SpostC. CONCLUSIONS SpostC reduced H/R injury in H9C2 embryonic rat cardiomyocytes by targeting the STRADA gene and by upregulating the expression of microRNA-107.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/genética , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Sevoflurano/farmacologia , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Apoptose/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Pós-Condicionamento Isquêmico/métodos , MicroRNAs/genética , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
17.
Sci China Life Sci ; 63(1): 59-67, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31872378

RESUMO

The zebrafish has become a popular vertebrate animal model in biomedical research. However, it is still challenging to make conditional gene knockout (CKO) models in zebrafish due to the low efficiency of homologous recombination (HR). Here we report an efficient non-HR-based method for generating zebrafish carrying a CKO and knockin (KI) switch (zCKOIS) coupled with dual-color fluorescent reporters. Using this strategy, we generated hey2zKOIS which served as a hey2 KI reporter with EGFP expression. Upon Cre induction in targeted cells, the hey2zCKOIS was switched to a non-functional CKO allele hey2zCKOIS-invassociated with TagRFP expression, enabling visualization of the CKO alleles. Thus, simplification of the design, and the visibility and combination of both CKO and KI alleles make our zCKOIS strategy an applicable CKO approach for zebrafish.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Sistemas CRISPR-Cas/genética , Marcação de Genes/métodos , Recombinação Homóloga/genética , Íntrons/genética , Proteínas de Peixe-Zebra/genética , Alelos , Animais , Animais Geneticamente Modificados , Sequência de Bases , Expressão Gênica , Técnicas de Introdução de Genes/métodos , Técnicas de Inativação de Genes/métodos , Engenharia Genética , Genótipo , Proteínas de Fluorescência Verde/genética , Peixe-Zebra
18.
Zhongguo Zhong Yao Za Zhi ; 44(14): 3078-3086, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602856

RESUMO

The element speciation analysis for heavy metals in herbal medicines is still in the beginning stage. In this study,the total amount of arsenic( As) in 103 batches of 17 commonly used Chinese medicines( including 16 plant medicines and 1 medicinal fungus) was detected by inductively coupled plasma mass spectrometry( ICP-MS). Furthermore,based on HPLC-ICP-MS,the simultaneous detection methods of six As speciation kinds in traditional Chinese medicines were established. An AS7 anion exchange column was selected and the As forms in 17 traditional Chinese medicines was systematically analyzed. The results showed that the method of pretreatment of medicinal materials by microwave digestion and the detection of total amount of As by ICP-MS was stable and reliable. As for the speciation analysis of As,the high-speed ultrasonic extraction method was adopted,and it showed that the linear relationship of the six As speciation was satisfied with the correlation coefficient R2>0. 999 9. The LOQ of six kinds of As speciation were 0. 20,0. 10,0. 15,0. 10,0. 25,0. 10 µg·L~(-1) for arsenic betaine( As B),arsenious acid [As( Ⅲ) ],dimethyl arsenic( DMA),arsenic choline( As C),monomethyl arsenic( MMA),arsenic acid[As( Ⅴ) ],respectively. The recoveries were between 84. 24% and 121. 5%,and the relative standard deviations were 2. 7% to 11%. Among the 103 batches of medicinal materials,only one batch of sample As exceeded the Chinese Pharmacopoeia limit standard; As( Ⅲ) and As( Ⅴ) had high detection rate in 103 batches of Chinese herbal medicines,within which As( Ⅴ) was the main detected form,and inorganic As accounted for the ratio reached 80. 90%-98. 73%; some samples detected DMA,MMA and As B,As C was not detected in any batch. This study established an analytical method suitable for the speciation of As in Chinese herbal medicines,and provided basic data for As residual residue in Chinese herbal medicines,which can provide important reference for the risk assessment and quality standards.


Assuntos
Arsênio/análise , Medicamentos de Ervas Chinesas/análise , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/normas , Espectrometria de Massas
19.
J Cell Biochem ; 120(8): 13985-13993, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30957285

RESUMO

Matrix attachment regions (MARs) can enhance transgene expression levels and maintain stability. However, the consensus sequence from MARs and its functional analysis remains to be examined. Here, we assessed a possible consensus sequence from MARs and assessed its activity in stably transfected Chinese hamster ovary (CHO) cells. First, we analyzed the effects of 10 MARs on transfected CHO cells and then analyzed the consensus motifs from these MARs using a bioinformatics method. The consensus sequence was synthesized and cloned upstream or downstream of the eukaryotic vector. The constructs were transfected into CHO cells and the expression levels and stability of enhanced green fluorescent protein were detected by flow cytometry. The results indicated that eight of the ten MARs increased transgene expression in transfected CHO cells. Three consensus motifs were found after bioinformatics analyses. The consensus sequence tandemly enhanced transgene expression when it was inserted into the eukaryotic expression vector; the effect of the addition upstream was stronger than that downstream. Thus, we found a MAR consensus sequence that may regulate the MAR-mediated increase in transgene expression.


Assuntos
Sequência Consenso/genética , Regiões de Interação com a Matriz/genética , Transfecção , Animais , Sequência de Bases , Células CHO , Cricetinae , Cricetulus , Dosagem de Genes , Expressão Gênica , Proteínas de Fluorescência Verde/metabolismo , Humanos , Proteínas Recombinantes/metabolismo , Transgenes
20.
Nat Prod Res ; 33(16): 2314-2321, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29480065

RESUMO

Three new acetophenones, named cynwilforones A-C (1-3), together with cynandione A (4) were isolated from the root bark of Cynanchum wilfordii (Maxim.) Hemsl. Their structures were deduced based on spectroscopic analysis and chemical methods. Compounds 1 and 4 exhibited potential hypoglycemic effects through inhibition of hepatic gluconeogenesis by down-regulating the expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. This is the first report that acetophenones from the root bark of C. wilfordii possesses potential hypoglycemic activity in vitro.


Assuntos
Acetofenonas/isolamento & purificação , Cynanchum/química , Hipoglicemiantes/farmacologia , Acetofenonas/química , Acetofenonas/farmacologia , Animais , Compostos de Bifenilo/isolamento & purificação , Células Cultivadas , Camundongos , Casca de Planta/química , Raízes de Plantas/química
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