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2.
Sensors (Basel) ; 20(5)2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32121408

RESUMO

Quick and effective detection of biothiols in biological fluids has gained increasing attention due to its vital biological functions. In this paper, a novel reversible fluorescence chemosensor (L-Cu2+) based on a benzocoumarin-Cu2+ ensemble has been developed for the detection of biothiols (Cys, Hcy and GSH) in human urine. The chemosensing ensemble (L-Cu2+) contains a 2:1 stoichiometry structure between fluorescent ligand L and paramagnetic Cu2+. L was found to exclusively bond with Cu2+ ions accompanied with a dramatic fluorescence quenching maximum at 443 nm and an increase of an absorbance band centered at 378 nm. Then, the in situ generated fluorescence sluggish ensemble, L-Cu2+, was successfully used as a chemosensor for the detection of biothiols with a fluorescence "OFF-ON" response modality. Upon the addition of biothiols, the decomplexation of L-Cu2+ led to the liberation of the fluorescent ligand, L, resulting in the recovery of fluorescence and absorbance spectra. Studies revealed that L-Cu2+ possesses simple synthesis, excellent stability, high sensitivity, reliability at a broad pH range and desired renewability (at least 5 times). The practical application of L-Cu2+ was then demonstrated by the detection of biothiols in human urine sample.

3.
Environ Pollut ; 262: 114278, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32146367

RESUMO

Exposure to atmospheric particulate matter (PM) has been related to the increasing incidence and mortality of pulmonary diseases, where microRNAs (miRNAs) play significant roles in these biological and pathological processes. In the present study, we found that miR-382-5p played an anti-inflammatory role in pulmonary inflammation induced by fine particulate matter (PM2.5) or diesel exhaust particles (DEPs) in vitro and in vivo. The expression level of miR-382-5p was downregulated, while its target gene, namely CXCL12, was elevated in HBE cells after exposure to PM2.5 or DEPs. Mechanistically, PM2.5 or DEPs exposure increased CXCL12/MMP9 expression via miR-382-5p inhibition, subsequently triggered pulmonary inflammation. Furthermore, antagonizing the function of CXCL12 significantly reduced the expression of MMP9 and local inflammation induced by PM2.5 or DEPs. PM2.5 or DEPs caused apoptosis and G1 phase arrest could be partially restored by overexpression of miR-382-5p and antagonism of CXCL12. In a murine model, enhanced miR-382-5p expression effectively reduced expression levels of CXCL12, MMP9 and inflammatory cytokines, hereby protected lung tissues against PM2.5 or DEPs-induced lesions. Collectively, the miR-382-5p/CXCL12/MMP9 pathway may provide a mechanism, which mediates inflammatory response to PM2.5 or DEPs exposure.

4.
Can J Anaesth ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32180175

RESUMO

PURPOSE: To assess the management and safety of epidural or general anesthesia for Cesarean delivery in parturients with coronavirus disease (COVID-19) and their newborns, and to evaluate the standardized procedures for protecting medical staff. METHODS: We retrospectively reviewed the cases of parturients diagnosed with severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection disease (COVID-19). Their epidemiologic history, chest computed tomography scans, laboratory measurements, and SARS-CoV-2 nucleic acid positivity were evaluated. We also recorded the patients' demographic and clinical characteristics, anesthesia and surgery-related data, maternal and neonatal complications, as well as the health status of the involved medical staff. RESULTS: The clinical characteristics of 17 pregnant women infected with SARS-CoV-2 were similar to those previously reported in non-pregnant adult patients. All of the 17 patients underwent Cesarean delivery with anesthesia performed according to standardized anesthesia/surgery procedures. Fourteen of the patients underwent continuous epidural anesthesia with 12 experiencing significant intraoperative hypotension. Three patients received general anesthesia with tracheal intubation because emergency surgery was needed. Three of the parturients are still recovering from their Cesarean delivery and are receiving in-hospital treatment for COVID-19. Three neonates were born prematurely. There were no deaths or serious neonatal asphyxia events. All neonatal SARS-CoV-2 nucleic acid tests were negative. No medical staff were infected throughout the patient care period. CONCLUSIONS: Both epidural and general anesthesia were safely used for Cesarean delivery in the parturients with COVID-19. Nevertheless, the incidence of hypotension during epidural anesthesia appeared excessive. Proper patient transfer, medical staff access procedures, and effective biosafety precautions are important to protect medical staff from COVID-19.

5.
Mol Cancer ; 19(1): 13, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31973707

RESUMO

BACKGROUND: As a novel class of noncoding RNAs, circRNAs have been recently identified to regulate tumorigenesis and aggressiveness. However, the function of circRNAs in colorectal cancer (CRC) metastasis remains unclear. We aimed to identify circRNAs that are upregulated in CRC tissues from patients and study their function in CRC metastasis. METHODS: We compared six pairs of CRC tissues and their matched adjacent non-tumor tissues by using circRNA microarray. We first evaluated the expression of circPTK2 (hsa_circ_0005273) in fresh tissues from CRC tumors and corresponding adjacent tissues by qPCR analysis. CircPTK2 expression levels in the tissue microarray with 5 years of survival information were determined by RNA-ISH analysis. Meanwhile, the expression levels of circulating circPTK2 were further analyzed according to the patients' clinical features. We analyzed cell apoptosis, colony formation, migration, and invasion in CRC cells. To further elucidate the effect of circPTK2 in CRC metastasis, we also conducted a colon cancer hepatic and pulmonary metastasis experiment. We used RNA biotin-labeled pull down and mass spectrometry to identify the target of circPTK2. We established a PDTX model to evaluate the effect of shRNA specifically targeting circPTK2 on tumor metastasis. RESULTS: We identified a novel circRNA, circPTK2, which is back-spliced of three exons (exons 27, 28 and 29) of PTK2 by using circRNA microarray, bioinformatics and functional studies. CircPTK2 was elevated in CRC tissues and positively associated with tumor growth and metastasis. CRC patients with increased circPTK2 expression were positively correlated with poorer survival rates. Furthermore, our studies showed that circPTK2 could promote EMT of CRC cells in vitro and in vivo by binding to vimentin protein on sites Ser38, Ser55 and Ser82. We further demonstrated the interaction of circPTK2 and vimentin mediated the regulation of CRC by knockdown or overexpression of vimentin. In addition, we revealed that tail vein injection of shRNA specifically targeting circPTK2 blunt tumor metastasis in a patient-derived CRC xenograft model. CONCLUSIONS: Collectively, these results demonstrate that circPTK2 exerts critical roles in CRC growth and metastasis and may serve as a potential therapeutic target for CRC metastasis, and also a promising biomarker for early diagnosis of metastasis.

6.
Environ Int ; 136: 105487, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31999974

RESUMO

BACKGROUND: The major components of traffic pollution particulate matter, diesel exhaust particles (DEPs), are airborne ultrafine particles (UFPs). DEPs can enter the central nervous system (CNS), where they may cause neurotoxicity. METHODS: We established murine models with intranasal DEPs instillation in male C57BL/6 and Nlrp3 knock-out (Nlrp3-/-) mice to investigate the effects of DEPs exposure on murine neurobehaviors and related mechanisms. Morris water maze (MWM) tests were performed to evaluate the learning and memory behaviors of mice following DEPs instillation. Metabolomics were assessed using an gas chromatography system coupled to a mass spectrometer. Real-time PCR and immunohistochemistry assays were used to analyze the mRNA and protein expression levels of target genes. Murine microglia, BV2 cells were employed to assay the effects of DEPs exposure in vitro. RESULTS: Intranasal administration of DEPs in mice led to impairment in hippocampal-dependent learning and memory. Moreover, this phenotype was linked to increased number of Iba-1+ microglia and NLRP3 inflammasome, as well as suppression of mitochondrial gene expression in the hippocampus of mice exposed to DEPs. Nlrp3-/- mice were resistant to DEPs-induced learning and memory impairment, concomitant with protection against the suppression of mitochondrial gene expression. Murine microglia cells (BV2) were exposed to DEPs in vitro and taurine was identified as one of the significantly suppressed metabolites in DEPs-treated microglia by metabolomics analysis. Supplementation with taurine efficiently rescued learning, memory and mitochondrial gene expression levels in the hippocampus of DEPs-exposed mice. CONCLUSIONS: Mechanistically, our study revealed that microglia-mediated NLRP3 inflammasome activation plays a deleterious role in DEPs-induced neurotoxicity by inhibiting mitochondrial gene expression. These results shed novel light on the potential value of nutritional supplementation against DEPs-induced neurotoxicity in individuals exposed to severe airborne traffic-related air pollutions.

7.
Environ Pollut ; 259: 113839, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31918133

RESUMO

Exposure to Aluminum oxide nanoparticles (Al2O3 NPs) has been associated with pulmonary inflammation in recent years; however, the underlying mechanism that causes adverse effects remains unclear. In the present study, we characterized microRNA (miRNA) expression profiling in human bronchial epithelial (HBE) cells exposed to Al2O3 NPs by miRNA microarray. Among the differentially expressed miRNAs, miR-297, a homologous miRNA in Homo sapiens and Mus musculus, was significantly up-regulated following exposure to Al2O3 NPs, compared with that in control. On combined bioinformatic analysis, proteomics analysis, and mRNA microarray, NF-κB-activating protein (NKAP) was found to be a target gene of miR-297 and it was significantly down-regulated in Al2O3 NPs-exposed HBE cells and murine lungs, compared with that in control. Meanwhile, inflammatory cytokines, including IL-1ß and TNF-α, were significantly increased in bronchoalveolar lavage fluid (BALF) from mice exposed to Al2O3 NPs. Then we set up a mouse model with intranasal instillation of antagomiR-297 to further confirm that inhibition of miR-297 expression can rescue pulmonary inflammation via Notch pathway suppression. Collectively, our findings suggested that up-regulation of miR-297 expression was an upstream driver of Notch pathway activation, which might be the underlying mechanism involved in lung inflammation induced by exposure to Al2O3 NPs.

8.
Adv Sci (Weinh) ; 6(18): 1900972, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31559135

RESUMO

Diesel exhaust particles (DEPs) are common airborne ultrafine particles (UFPs); however, few studies have examined their effects on the gastrointestinal tract. To investigate the interaction of gut microbiota and DEPs-induced colonic injury, adult C57BL/6 mice are kept in whole-body inhalation chambers and exposed to filtered room air (FRA) or DEPs (300 µg m-3) 1 h per day for 28 consecutive days. DEPs exposure results in colon epithelial injury with inflammatory cell infiltration and mucus depletion. Abundance of Lactobacillus in murine feces is transiently increased following 7-day DEPs exposure and then decreased until the end of 28-day exposure. A reduction of the colonic mucus layer thickness is observed in mice receiving gut microbiota from DEPs-exposed mice. Mechanistically, RNA-sequencing suggests disruption of the nitrogen metabolism pathway in DEPs-exposed NCM460 cells. Upregulation of carbonic anhydrase 9 (CA9) expression levels is observed in epithelia following DEPs exposure both in vivo and in vitro. Oral administration of probiotics protects the mice against DEPS-induced colon epithelial injury. The results strongly suggest the involvement of gut microbiota in response to DEPs exposure and subsequently epithelial injury in vivo. Supplementation with probiotic may be a potential way to protect against UFPs-induced colon epithelial injury.

9.
Cancer Res ; 79(19): 4882-4895, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31409641

RESUMO

Immune dysregulation plays a vital role in colorectal cancer initiation and progression. Long noncoding RNAs (lncRNA) exhibit multiple functions including regulation of gene expression. Here, we identified an immune-related lncRNA, MIR17HG, whose expression was gradually upregulated in adjacent, adenoma, and colorectal cancer tissue. MIR17HG promoted tumorigenesis and metastasis in colorectal cancer cells both in vitro and in vivo. Mechanistically, MIR17HG increased the expression of NF-κB/RELA by competitively sponging the microRNA miR-375. In addition, RELA transcriptionally activated MIR17HG in a positive feedback loop by directly binding to its promoter region. Moreover, miR-17-5p, one of the transcribed miRNAs from MIR17HG, reduced the expression of the tumor suppressor B-cell linker (BLNK), resulting in increased migration and invasion of colorectal cancer cells. MIR17HG also upregulated PD-L1, indicating its potential role in immunotherapy. Overall, these findings demonstrate that MIR17HG plays an oncogenic role in colorectal cancer and may serve as a promising therapeutic target. SIGNIFICANCE: These findings provide mechanistic insight into the role of the lncRNA MIR17HG and its miRNA members in regulating colorectal cancer carcinogenesis and progression.

10.
Neuroscience ; 417: 70-80, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31430527

RESUMO

Neuroinflammation in the hippocampus plays essential roles in postoperative cognitive dysfunction (POCD). Histone deacetylases (HDACs) have recently been identified as key regulators of neuroinflammation. MS-275, an inhibitor of HDAC, has been reported to have neuroprotective effects. Therefore, the present study aimed to test the hypothesis that pretreatment with MS-275 prevents POCD by inhibiting neuroinflammation in rats. In this study, anesthesia/surgery impaired cognition, demonstrated by an increase escape latency and reduction in the number of platform crossings in Morris water maze (MWM) trials, through activating microglia neuroinflammation and decreasing PSD-95 expression. However, pretreatment with MS-275 attenuated postoperative cognitive impairment severity. Furthermore, pretreatment with MS-275 decreased activated microglia levels and increased PSD95 protein expression in the hippocampus. Pretreatment with MS-275 reduced NF-κB-p65 protein expression and nuclear accumulation as well as the neuroinflammatory response (production of proinflammatory cytokines including TNF-α and IL-1ß) in the hippocampus. Additionally, MS-275 reduced HDAC2 expression and HDAC activity in the hippocampus, which were enhanced in vehicle-treated rats. These results suggest that MS-275 alleviates postoperative cognitive dysfunction by reducing neuroinflammation in the hippocampus of rats via HDAC inhibition.

11.
J Biochem ; 166(5): 415-421, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31297532

RESUMO

Reducing oxidative stress is an effective method to prevent hepatic ischaemia/reperfusion injury (HIRI). This study focuses on the role of propofol on the oxidative stress of hepatic cells and the involved lncRNA-TUG1/Brahma-related gene 1 (Brg1) pathway in HIRI mice. The mouse HIRI model was established and was intraperitoneally injected with propofol postconditioning. Hepatic injury indexes were used to evaluate HIRI. The oxidative stress was indicated by increasing 8-isoprostane concentration. Mouse hepatic cell line AML12 was treated with hypoxia and subsequent reoxygenation (H/R). The targeted regulation of lncRNA-TUG1 on Brg1 was proved by RNA pull-down, RIP (RNA-binding protein immunoprecipitation) and the expression level of Brg1 responds to silencing or overexpression of lncRNA-TUG1. Propofol alleviates HIRI and induces the upregulation of lncRNA-TUG1 in the mouse HIRI model. Propofol increases cell viability and lncRNA-TUG1 expression level in H/R-treated hepatic cells. In H/R plus propofol-treated hepatic cells, lncRNA-TUG1 silencing reduces cell viability and increased oxidative stress. LncRNA-TUG1 interacts with Brg1 protein and keeps its level via inhibiting its degradation. Brg1 overexpression reverses lncRNA-TUG1 induced the reduction of cell viability and the increase in oxidative stress. LncRNA-TUG1 silencing abrogates the protective role of propofol against HIRI in the mouse HIRI model. LncRNA-TUG1 has a targeted regulation of Brg1, and thereby affects the oxidative stress induced by HIRI. This pathway mediates the protective effect of propofol against HIRI of hepatic cell.


Assuntos
DNA Helicases/metabolismo , Hepatócitos/efeitos dos fármacos , Hipóxia/tratamento farmacológico , Proteínas Nucleares/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxigênio/metabolismo , Propofol/farmacologia , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismo , Animais , Hepatócitos/metabolismo , Hipóxia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regulação para Cima/efeitos dos fármacos
12.
Molecules ; 24(13)2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31277409

RESUMO

We report the development of a new colorimetric probe (L-ol) for investigations of the redox process regulated by hypochlorous acid (HOCl) and glutathione (GSH). The HOCl/GSH redox-switching cycle process was investigated in detail by UV-vis absorption spectroscopy, colorimetric analysis assay and high-resolution mass spectrometry (HRMS). The switchable absorbance responses were attributed to the HOCl-induced oxidation of the p-methoxyphenol unit to the benzoquinone derivative (L-one) and sequential reduction of L-one to hydroquinone (L-ol') by GSH. In phosphate-buffered saline (PBS) buffer, the absorbance of L-ol at 619 nm underwent a remarkable bathochromic-shift, accompanied by a color change from pale yellow to blue in the presence of HOCl. With further addition of GSH, the absorbance of L-one exclusively recovered to the original level. Meanwhile, the blue-colored solution returned to the naive pale yellow color in the presence of GSH. The detection limits for HOCl and GSH were calculated to be 6.3 and 96 nM according to the IUPAC criteria. Furthermore, L-ol-loaded chromatography plates have been prepared and successfully applied to visualize and quantitatively analyze HOCl in several natural waters.


Assuntos
Colorimetria/métodos , Glutationa/análise , Ácido Hipocloroso/análise , Benzoquinonas/química , Cor , Hidroquinonas/química , Sondas Moleculares/síntese química , Sondas Moleculares/química , Oxirredução , Espectrofotometria Ultravioleta , Fatores de Tempo , Água/química
13.
Cancer Res ; 79(20): 5432-5441, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31311811

RESUMO

Metastasis associated with lung adenocarcinoma transcript-1 (MALAT1) is an evolutionarily highly conserved lncRNA that contributes to colorectal cancer development. However, the exact molecular mechanisms connecting MALAT1 to colorectal cancer have not been fully elucidated. Here, we performed a case-control study in 1,078 patients with colorectal cancer and 1,175 healthy controls to evaluate the association between potentially functional genetic variants of MALAT1 and survival outcomes in patients with colorectal cancer. MALAT1 rs664589 CG/GG genotypes significantly increased the associated risk and decreased overall survival of patients with colorectal cancer compared with the CC genotype. In vitro and in vivo experiments showed that the rs664589 C to G mutation facilitated carcinogenesis and metastasis of colorectal cancer. Mechanistically, the miRNA miR-194-5p targeted MALAT1 for degradation in the nucleus in an Ago2-dependent manner; the rs664589 G allele altered the binding of MALAT1 to miR-194-5p, resulting in increased expression of MALAT1. Colorectal cancer cells and human tissues with the rs664589 CG/GG genotype expressed significantly higher MALAT1 than those with the rs664589 CC genotype. Multivariate Cox regression analysis showed that MALAT1 was a poor prognostic factor of colorectal cancer. In summary, MALAT1 with the rs664589 G allele demonstrates altered binding to miR-194-5p in the nucleus, leading to increased MALAT1 expression and enhanced colorectal cancer development. SIGNIFICANCE: These findings highlight the functional role of MALAT1 polymorphism in colorectal cancer metastasis and survival as well as the underlying mechanism.

14.
Adv Sci (Weinh) ; 6(11): 1900180, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31179224

RESUMO

Particulate matter (PM) exposure has been associated with intestinal disorders. Therefore, there is an urgent need to understand the precise molecular mechanism involved and explore potential prevention strategies. In this study, inhaled PM is shown to activate inflammatory pathways in murine colon. In a panel study, it is found that ambient PM levels are significantly associated with elevated number of fecal white blood cells in healthy subjects. Acting as a promoter, PM exposure accelerates chemical carcinogenesis-induced colonic tumor formation in a murine model. Mechanistically, RNA-seq assays suggest activation of phosphoinositide 3-kinase (PI3K)/AKT cascades in chronically PM-exposed human colon mucosal epithelial cells. Ablation of up-stream driver fibroblast growth factor receptor 4 (FGFR4) effectively inhibits inflammation and neoplasia in PM-exposed murine colons. Notably, dietary curcumin supplement is shown to protect against PM-induced colonic injuries in mice. Collectively, these findings identify that PM exposure accelerates colonic tumorigenesis in a PI3K/AKT-dependent manner and suggests potential nutrient supplement for prevention.

15.
J Mol Neurosci ; 69(1): 106-114, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31190218

RESUMO

Microglial cell activation after spinal cord ischemia-reperfusion injury (SCIRI) commonly causes the secondary nerve motion function injury. This study aims to study the mechanism by which the drug dexmedetomidine (DEX) inhibits microglial cell activation and improves motion function of SCIRI mice. Mice SCIRI model was established, and microglia from spinal cord were isolated and cultured for subsequent molecule analysis of let-7a-1-3p, let-7a-2-3p, HMGB1, TNF-α, and IL-6. DEX was given by intraperitoneal injection. Mice motion function was evaluated by Basso mouse score. In vitro microglial cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) to imitate ischemia-reperfusion injury stimulation. DEX injection improves the mouse motion function in SCIRI model and upregulates let-7a-1/2-3p expression in the isolated activated microglia from SCIRI mice. In OGD/R-stimulated microglia, DEX treatment also caused the inactivation of cells, the upregulation of let-7a-1/2-3p expression, and the downregulation of HMGB1 expression. While the co-silencing of let-7a-1/2-3p in microglia in addition to DEX treatment restored the activation of microglia. HMGB1 is a targeted gene for let-7a-1/2-3p and negatively regulated by them. HMGB1 knockdown abrogates the pro-activation impact on microglial cell by let-7a-1/2-3p silencing. DEX inhibits the activation of microglial cell in the spinal cord of SCIRI mice, mediated by the let-7a-1/2-3p/HMGB1 pathway.


Assuntos
Analgésicos não Entorpecentes/farmacologia , Dexmedetomidina/farmacologia , Proteína HMGB1/genética , MicroRNAs/metabolismo , Microglia/metabolismo , Traumatismo por Reperfusão/metabolismo , Medula Espinal/metabolismo , Analgésicos não Entorpecentes/uso terapêutico , Animais , Células Cultivadas , Dexmedetomidina/uso terapêutico , Proteína HMGB1/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Microglia/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Medula Espinal/irrigação sanguínea , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
16.
Nat Rev Cardiol ; 16(10): 602-611, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31150009

RESUMO

Polypills can contain multiple pharmaceutical agents targeting the cardiovascular system. The use of polypills in the secondary prevention of cardiovascular disease (CVD) has received broad support; however, the use of polypills in the primary prevention of CVD is more controversial. This controversy stems from an inherent resistance to the medicalization of primary prevention, and the lower CVD event rate in this population means that smaller absolute benefits are derived. Indeed, drug-related adverse effects, such as from aspirin, might even outweigh the benefits. The role of fixed-dose combination (FDC) therapy for blood pressure (BP) lowering in combatting the widespread undertreatment of high BP - the leading modifiable risk factor contributing to the global burden of CVD - has gained momentum. Increasing evidence suggests that FDC pills containing multiple low doses of BP-lowering drugs produce more effective BP lowering than the use of fewer separate BP-lowering drugs at higher doses, without an increase in adverse effects. Trials of FDC pills comprising three half-dose or four quarter-dose BP-lowering drugs have shown substantial efficacy. In this Review, we summarize the current evidence on low-dose BP-lowering FDC pills and the justification for this approach in the context of polypills in the primary prevention of CVD.


Assuntos
Anti-Hipertensivos/uso terapêutico , Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Doença das Coronárias/prevenção & controle , Combinação de Medicamentos , Humanos , Hipertensão/tratamento farmacológico , Prevenção Primária/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/prevenção & controle
17.
Rev. bras. anestesiol ; 69(2): 160-167, Mar.-Apr. 2019. graf
Artigo em Inglês | LILACS-Express | ID: biblio-1003397

RESUMO

Abstract Background and objectives: Dexmedetomidine has demonstrated protective effects against lung injury in vitro. Here, we investigated whether dexmedetomidine preconditioning protected against lung injury in hemorrhagic shock rats. Methods: Male Sprague-Dawley rats were randomly divided into four groups (n = 8): control group, hemorrhagic shock group, 5 ug.kg-1 dexmedetomidine (DEX1) group, and 10 ug.kg-1 dexmedetomidine (DEX2) group. Saline or dexmedetomidine were administered over 20 min. 30 min after injection, hemorrhage was initiated in the hemorrhagic shock, DEX1 and DEX2 group. Four hours after resuscitation, protein and cellular content in bronchoalveolar lavage fluid, and the lung histopathology were measured. The malondialdehyde, superoxide dismutase, Bcl-2, Bax and caspase-3 were also tested in the lung tissue. Results: Compare with hemorrhagic shock group, 5 ug.kg-1 dexmedetomidine pretreatment reduced the apoptosis (2.25 ± 0.24 vs. 4.12 ± 0.42%, p < 0.05), histological score (1.06 ± 0.12 vs. 1.68 ± 0.15, p < 0.05) and protein (1.92 ± 0.38 vs. 3.95 ± 0.42 mg.mL-1, p < 0.05) and WBC (0.42 ± 0.11 vs. 0.92 ± 0.13 × 109/L, p < 0.05) in bronchoalveolar lavage fluid. Which is correlated with increased superoxide dismutase activity (8.35 ± 0.68 vs. 4.73 ± 0.44 U.mg-1 protein, p < 0.05) and decreased malondialdehyde (2.18 ± 0.19 vs. 3.28 ± 0.27 nmoL.mg-1 protein, p < 0.05). Dexmedetomidine preconditioning also increased the Bcl-2 level (0.55 ± 0.04 vs. 0.34 ± 0.05, p < 0.05) and decreased the level of Bax (0.46 ± 0.03 vs. 0.68 ± 0.04, p < 0.05), caspase-3 (0.49 ± 0.03 vs. 0.69 ± 0.04, p < 0.05). However, we did not observe any difference between the DEX1 and DEX2 groups for these (p > 0.05). Conclusion: Dexmedetomidine preconditioning has a protective effect against lung injury caused by hemorrhagic shock in rats. The potential mechanisms involved are the inhibition of cell death and improvement of antioxidation. But did not show a dose-dependent effect.


Resumo Justificativa e objetivos: Dexmedetomidina demonstrou efeitos protetores contra a lesão pulmonar in vitro. Neste estudo, investigamos se o pré-condicionamento com dexmedetomidina protege contra a lesão pulmonar em ratos com choque hemorrágico. Métodos: Ratos machos, Sprague-Dawley, foram aleatoriamente divididos em quatro grupos (n = 8): grupo controle, grupo com choque hemorrágico, grupo com 5 µg.kg-1 de dexmedetomidina (DEX1) e grupo com 10 µg.kg-1 de dexmedetomidina (DEX2). Solução salina ou dexmedetomidina foi administrada durante 20 minutos. Trinta minutos após a injeção, a hemorragia foi iniciada nos grupos choque hemorrágico, DEX1 e DEX2. Quatro horas após a ressuscitação, a proteína e o conteúdo celular no lavado broncoalveolar e a histopatologia pulmonar foram medidos. Malondialdeído, superóxido dismutase, Bcl-2, Bax e caspase-3 também foram testados no tecido pulmonar. Resultados: Na comparação com o grupo choque hemorrágico, o pré-tratamento com 5 ug.kg-1 de dexmedetomidina reduziu a apoptose (2,25 ± 0,24 vs. 4,12 ± 0,42%, p < 0,05), escore histológico (1,06 ± 0,12 vs. 1,68 ± 0,15, p < 0,05) e proteína (1,92 ± 0,38 vs. 3,95 ± 0,42 mg.mL-1, p < 0,05) e leucócitos (0,42 ± 0,11 vs. 0,92 ± 0,13 × 109/L, p < 0,05) no lavado broncoalveolar; o que está correlacionado com o aumento da atividade da superóxido dismutase (8,35 ± 0,68 vs. 4,73 ± 0,44 U.mg-1 de proteína, p < 0,05) e diminuição do malondialdeído (2,18 ± 0,19 vs. 3,28 ± 0,27 nmoL.mg-1 de proteína, p < 0,05). O pré-condicionamento com dexmedetomidina também aumentou o nível de Bcl-2 (0,55 ± 0,04 vs. 0,34 ± 0,05, p < 0,05) e diminuiu o nível de Bax (0,46 ± 0,03 vs. 0,68 ± 0,04, p < 0,05), caspase-3 (0,49 ± 0,03 vs. 0,69 ± 0,04, p < 0,05). No entanto, não houve diferença entre os grupos DEX1 e DEX2 para essas proteínas (p > 0,05). Conclusão: O pré-condicionamento com dexmedetomidina tem um efeito protetor contra a lesão pulmonar causada por choque hemorrágico em ratos. Os potenciais mecanismos envolvidos são a inibição da morte celular e a melhora da antioxidação. Porém, não mostrou um efeito dose-dependente.

18.
J Agric Food Chem ; 67(15): 4375-4383, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30865447

RESUMO

The development of new methods for rapid and effective detection of bisulfite (HSO3-) in food samples and imaging of HSO3- intake in animals is of significant importance due to the key roles of HSO3- in food quality assurance and community health. In this work, a new responsive fluorescence probe, EQC, is reported for the quantitative detection of HSO3- in food samples and visualization of HSO3- intake in animals. Upon addition of HSO3-, the UV-vis absorption and red emission of EQC were significantly decreased within 120 s. The changes in absorption and emission spectra of EQC were rationalized by theoretical computations. The proposed reaction mechanism of EQC with HSO3- was confirmed by high-resolution mass spectrometry (HRMS) and spectroscopic titration measurements. EQC has the advantages of high sensitivity, selectivity (a detection limit of 18.1 nM), and fast response toward HSO3-, which enable rapid and effective HSO3- detection in buffer solution. The practical applications of EQC were demonstrated by the detection of HSO3- in food samples and the imaging of HSO3- intake in live animals.


Assuntos
Corantes Fluorescentes/química , Análise de Alimentos/métodos , Espectrometria de Fluorescência/métodos , Sulfitos/análise , Animais , Feminino , Fluorescência , Contaminação de Alimentos/análise , Limite de Detecção , Masculino , Camundongos , Camundongos Nus , Vinho/análise , Peixe-Zebra
19.
Small ; 15(32): e1804770, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30714307

RESUMO

The effective synthesis of chiral compounds in a highly enantioselective manner is obviously attractive. Inspired by the enzymatic reactions that occur in pocket-like cavities with high efficiency and specificity, chemists are seeking to construct catalysts that mimic this key feature of enzymes. Recent progress in supramolecular coordination chemistry has shown that metal-organic cages (MOCs) and metal-organic frameworks (MOFs) with chiral confined cavities/pores may offer a novel platform for achieving asymmetric catalysis with high enantioselectivity. The inherent chiral confined microenvironment is considered to be analogous to the binding pocket of enzymes, and this pocket promotes enantioselective transformations. This work focuses on the recent advances in MOCs and MOFs with chiral confined spaces for asymmetric catalysis, and each section is separated into two parts based on how the chirality is achieved in these metal-organic architectures. A special emphasis is placed on discussing the relationship between the enantioselectivity and the confined spaces of the chiral functional MOCs and MOFs rather than catalytic chemistry. Finally, current challenges and perspectives are discussed. This work is anticipated to offer researchers insights into the design of sophisticated chiral confined space-based metal-organic architectures for asymmetric catalysis with high enantioselectivity.

20.
Rev Bras Anestesiol ; 69(2): 160-167, 2019.
Artigo em Português | MEDLINE | ID: mdl-30655009

RESUMO

BACKGROUND AND OBJECTIVES: Dexmedetomidine has demonstrated protective effects against lung injury in vitro. Here, we investigated whether dexmedetomidine preconditioning protected against lung injury in hemorrhagic shock rats. METHODS: Male Sprague-Dawley rats were randomly divided into four groups (n=8): control group, hemorrhagic shock group, 5ug.kg-1 dexmedetomidine (DEX1) group, and 10ug.kg-1 dexmedetomidine (DEX2) group. Saline or dexmedetomidine were administered over 20min. 30min after injection, hemorrhage was initiated in the hemorrhagic shock, DEX1 and DEX2 group. Four hours after resuscitation, protein and cellular content in bronchoalveolar lavage fluid, and the lung histopathology were measured. The malondialdehyde, superoxide dismutase, Bcl-2, Bax and caspase-3 were also tested in the lung tissue. RESULTS: Compare with hemorrhagic shock group, 5ug.kg-1 dexmedetomidine pretreatment reduced the apoptosis (2.25±0.24 vs. 4.12±0.42%, p<0.05), histological score (1.06±0.12 vs. 1.68±0.15, p<0.05) and protein (1.92±0.38 vs. 3.95±0.42mg.mL-1, p<0.05) and WBC (0.42±0.11 vs. 0.92±0.13×109/L, p<0.05) in bronchoalveolar lavage fluid. Which is correlated with increased superoxide dismutase activity (8.35±0.68 vs. 4.73±0.44U.mg-1 protein, p<0.05) and decreased malondialdehyde (2.18±0.19 vs. 3.28±0.27nmoL.mg-1 protein, p<0.05). Dexmedetomidine preconditioning also increased the Bcl-2 level (0.55±0.04 vs. 0.34±0.05, p<0.05) and decreased the level of Bax (0.46±0.03 vs. 0.68±0.04, p<0.05), caspase-3 (0.49±0.03 vs. 0.69±0.04, p<0.05). However, we did not observe any difference between the DEX1 and DEX2 groups for these (p>0.05). CONCLUSION: Dexmedetomidine preconditioning has a protective effect against lung injury caused by hemorrhagic shock in rats. The potential mechanisms involved are the inhibition of cell death and improvement of antioxidation. But did not show a dose-dependent effect.


Assuntos
Dexmedetomidina/administração & dosagem , Lesão Pulmonar/prevenção & controle , Substâncias Protetoras/administração & dosagem , Choque Hemorrágico/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar , Dexmedetomidina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Lesão Pulmonar/etiologia , Masculino , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Choque Hemorrágico/complicações
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