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1.
Vascular ; : 1708538120985732, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478353

RESUMO

OBJECTIVES: To compare the safety and efficiency of atherectomy plus drug-coated balloon with drug-coated balloon only for the treatment of femoropopliteal artery lesions. METHODS: This systematic review and meta-analysis was performed and reported following the requirement of the PRISMA. EMBASE, MEDLINE, and Cochrane library were queried from January 2000 to June 2020 to identify eligible literature. The modified Downs and Black checklist was used to assess the quality of included studies. Outcome measures included bail-out stenting, distal embolization, perforation, hematoma, primary patency at 12 months, target lesion revascularization at 12 months, leg amputation at 12 months, and mortality at 12 months. We used DerSimonian and Laird random-effects model to pool the dichotomous data on risk ratio (RR) with 95% confidence intervals (CIs) from each study to obtain an overall estimate for major outcomes. Subgroup analysis and sensitivity analyses were conducted. RESULTS: Six studies (two randomized controlled trials and four retrospective cohort studies) with 470 patients were included. Atherectomy plus drug-coated balloon group was associated with lower rates of bail-out stenting (RR: 0.49, 95%CI: 0.34-0.71, P < 0.001). There was no significant difference between two groups in terms of distal embolization (RR: 2.06, 95%CI: 0.51-8.38, P = 0.31), perforation (RR: 2.04, 95%CI: 0.43-9.71, P = 0.37), hematoma (RR: 1.75, 95%CI: 0.43-7.09, P = 0.43), primary patency at 12 months (1.09, 95%CI: 0.98-1.21, P = 0.12), target lesion revascularization at 12 months (RR: 0.68, 95%CI: 0.41-1.14, P = 0.15), leg amputations at 12 months (RR: 0.54, 95%CI: 0.13-2.23, P = 0.39), mortality at 12 months (RR: 2.18, 95%CI: 0.71-6.64, P = 0.17). Sensitivity analysis had no effect on our findings. CONCLUSIONS: The combination of atherectomy and drug-coated balloon was safe and effective in the treatment of femoropopliteal artery lesions, with lower incidence of bail-out stenting compared with drug-coated balloon only.

3.
ACS Omega ; 5(47): 30587-30595, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33283107

RESUMO

This study aimed to explore the dynamic variations in the phenolic and volatile organic compounds of sugarcane vinegar subjected to different production processes. The determination of phenolic and volatile organic compounds was performed by UPLC-MS and solid phase micro extraction (SPME) coupled with gas chromatography combined with mass spectrometry (GC-MS). The complete fermentation process of sugarcane lasted nine days, and production of vinegar of up to 3.04% (w/v), total acids, and 4.1° alcoholicity was accomplished. Various phenolic compounds of sugarcane juice (non-sterilized) and those of alcoholic and acetic acid fermentation were obtained after nine days of fermentation. These were benzoic acid (2.024, 1.002, and 1.027 mg L-1), ferulic acid (0.060, 0.205, and 1.124 mg L-1), quinic acid (0.019, 0.074, and 0.031 mg L-1), chlorogenic acid (0.349, 1.635, and 1.217 mg L-1), apigenin (0.002, 0.099, and 0.004 mg L-1), kaempferol (0.003, 0.336, and 0.003 mg L-1), caffeic acid (-, 0.005, and 0.005 mg L-1), luteolin (0.003, 0.323, and 0.005 mg L-1), and p-coumaric acid (0.018, 0.015, and 0.027 mg L-1). Forty-five volatile organic compounds were also identified. The sugarcane juice can be commercialized as an alternative to wine as it presents characteristics of an alcoholic fermented beverage.

4.
J Am Chem Soc ; 142(51): 21243-21248, 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33315385

RESUMO

Electrically conductive metal-organic frameworks (cMOFs) have become a topic of intense interest in recent years because of their great potential in electrochemical energy storage, electrocatalysis, and sensing applications. Most of the cMOFs reported hitherto are 2D structures, and 3D cMOFs remain rare. Herein we report FeTHQ, a 3D cMOF synthesized from tetrahydroxy-1,4-quinone (THQ) and iron(II) sulfate salt. FeTHQ exhibited a conductivity of 3.3 ± 0.55 mS cm-1 at 300 K, which is high for 3D cMOFs. The conductivity of FeTHQ is valence-dependent. A higher conductivity was measured with the as-prepared FeTHQ than with the air-oxidized and sodium naphthalenide-reduced samples.

5.
J Am Chem Soc ; 142(49): 20531-20535, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33226798

RESUMO

Conductive metal-organic frameworks (c-MOFs) have drawn increasing attention for their outstanding performance in energy-related applications. However, the majority of reported c-MOFs are based on 2D structures. Synthetic strategies for 3D c-MOFs are under-explored, leaving unrealized functionality in both their structures and properties. Herein we report Zn-HAB, a 3D c-MOF comprised of hexaaminobenzene and Zn(II). Zn-HAB is shown to have microporosity with a band gap of approximately 1.68 eV, resulting in a moderate conductivity of 0.86 mS cm-1 and a high Seebeck coefficient of 200 µV K-1 at 300 K. The power factor of 3.44 nW m-1 K-2 constitutes the first report of the thermoelectric properties of an intrinsically conductive 3D MOF.

6.
PeerJ ; 8: e10154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194396

RESUMO

In the dynamic era of climate change, agricultural farming systems are facing various unprecedented problems worldwide. Drought stress is one of the serious abiotic stresses that hinder the growth potential and crop productivity. Silicon (Si) can improve crop yield by enhancing the efficiency of inputs and reducing relevant losses. As a quasi-essential element and the 2nd most abundant element in the Earth's crust, Si is utilized by plants and applied exogenously to combat drought stress and improve plant performance by increasing physiological, cellular and molecular responses. However, the physiological mechanisms that respond to water stress are still not well defined in Saccharum officinarum plants. To the best of our knowledge, the dynamics of photosynthesis responsive to different exogenous Si levels in Saccharum officinarum has not been reported to date. The current experiment was carried out to assess the protective role of Si in plant growth and photosynthetic responses in Saccharum officinarum under water stress conditions. Saccharum officinarum cv. 'GT 42' plants were subjected to drought stress conditions (80-75%, 55-50% and 35-30% of soil moisture) after ten weeks of normal growth, followed by the soil irrigation of Si (0, 100, 300 and 500 mg L-1) for 8 weeks. The results indicated that Si addition mitigated the inhibition in Saccharum officinarum growth and photosynthesis, and improved biomass accumulation during water stress. The photosynthetic responses (photosynthesis, transpiration and stomatal conductance) were found down-regulated under water stress, and it was significantly enhanced by Si application. No phytotoxic effects were monitored even at excess (500 mg L-1). Soil irrigation of 300 mg L-1 of Si was more effective as 100 and 500 mg L-1 under water stress condition. It is concluded that the stress in Saccharum officinarum plants applied with Si was alleviated by improving plant fitness, photosynthetic capacity and biomass accumulation as compared with the control. Thus, this study offers new information towards the assessment of growth, biomass accumulation and physiological changes related to water stress with Si application in plants.

7.
ACS Omega ; 5(37): 24145-24153, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32984737

RESUMO

Silicon (Si) plays an important role in the sustainable agriculture industry. The increasing demand for crop production with a significant reduction of synthetic chemical fertilizers and pesticide use is a big challenge nowadays. The use of Si has been proven to be an environmentally sound way of enhancing crop productivity by facilitating plant growth and development through either a direct or indirect mechanism, especially in tropical and subtropical regions. In particular, it has been investigated for its role in water stress management. The aim of the current experiment was to examine the protective role of Si in the photosynthetic capacity of different leaf segments and the ultrastructure of sugarcane (Saccharum officinarm) plants under water stress. Sugarcane cv. GT 42 plants were supplied with 0, 100, 300, and 500 mg L-1 Si and exposed for 60 days under each stress condition such as 100-95, 55-50, and 35-30% of field capacity. For the photosynthetic responses, each leaf was observed and separated into three equal parts (base, middle, and tip). We used intact leaves and were able to assess leaf photosynthetic responses. Under moderate and severe stress conditions, applied Si increased the photosynthesis (base, ∼16-143%; middle, 20-66%; and tip leaf part, 41-71%), transpiration rate (base, 15-97%; middle, 26-68%; and tip leaf part, 6-61%), and stomatal conductance (base, 26-137%; middle, 12-70%; and tip leaf part, 7-75%) in sugarcane plants. Ultrastructural examination of sugarcane leaves using scanning electron microscopy showed the remarkable effects on stomata ultrastructure. Silicon increased plant growth development, photosynthetic efficiency, and biomass/yield, and promoted better adaptation of stomata to drought. This study suggests that the application of Si may be used to increase the stress tolerance of sugarcane plants.

8.
Angew Chem Int Ed Engl ; 59(10): 4043-4050, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-31919948

RESUMO

Ni,N-doped carbon catalysts have shown promising catalytic performance for CO2 electroreduction (CO2 R) to CO; this activity has often been attributed to the presence of nitrogen-coordinated, single Ni atom active sites. However, experimentally confirming Ni-N bonding and correlating CO2 reduction (CO2 R) activity to these species has remained a fundamental challenge. We synthesized polyacrylonitrile-derived Ni,N-doped carbon electrocatalysts (Ni-PACN) with a range of pyrolysis temperatures and Ni loadings and correlated their electrochemical activity with extensive physiochemical characterization to rigorously address the origin of activity in these materials. We found that the CO2 R to CO partial current density increased with increased Ni content before plateauing at 2 wt % which suggests a dispersed Ni active site. These dispersed active sites were investigated by hard and soft X-ray spectroscopy, which revealed that pyrrolic nitrogen ligands selectively bind Ni atoms in a distorted square-planar geometry that strongly resembles the active sites of molecular metal-porphyrin catalysts.

9.
Acta Biomater ; 100: 52-60, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31606530

RESUMO

Vascular stiffening is associated with the prognosis of cardiovascular disease (CVD). Endothelial dysfunction, as shown by reduced vasodilation and increased vasoconstriction, not only affects vascular tone, but also accelerates the progression of CVD. However, the precise effect of vascular stiffening on endothelial function and its mechanism is unclear and a possible underlying has not been determined. In this study, we found that increasing substrate stiffness promoted endothelin-1 (ET-1) expression and inhibited endothelial nitric oxide synthase expression in human umbilical vein endothelial cells. Additionally, miR-6740-5p was identified as a stiffness-sensitive microRNA, which was downregulated by a stiff substrate, resulting in increased ET-1 expression. Furthermore, we found that substrate stiffening reduced the expression and activity of the calcium channel TRPV4, which subsequently enhanced ET-1 expression by inhibiting miR-6740-5p. Finally, analysis of clinical plasma samples showed that plasma miR-6740-5p levels in patients with carotid atherosclerosis were significantly lower than those in healthy people. Taken together, our findings show a novel mechanically regulated TRPV4/miR-6740/ET-1 signaling axis by which substrate stiffness affects endothelial function. Our findings indicate that vascular stiffening induces endothelial dysfunction, thereby accelerating progression of CVD. Furthermore, this study indicates that endothelial dysfunction induced by improper biophysical cues from cardiovascular implants may be an important reason for complications arising from the use of cardiovascular implants. STATEMENT OF SIGNIFICANCE: Cardiovascular disease is the leading cause of morbidity and mortality worldwide. The incidence of cardiovascular disease is accompanied by increased vascular stiffness. Our work indicated that increased vascular stiffness accelerates the development of cardiovascular disease by inducing endothelial dysfunction, which is a key contributor to the pathogenesis of cardiovascular disease. In addition, we identified a novel underlying molecular pathophysiological mechanism by which increased stiffness induce endothelial dysfunction. Our work could help determine the pathogenesis of cardiovascular disease induced by biomechanical factors.


Assuntos
Endotelina-1/metabolismo , Matriz Extracelular/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Mecanotransdução Celular , MicroRNAs/metabolismo , Canais de Cátion TRPV/metabolismo , Sinalização do Cálcio , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/genética , Estudos de Casos e Controles , Adesão Celular , Citoesqueleto/metabolismo , Citosol/metabolismo , Feminino , Regulação da Expressão Gênica , Células HEK293 , Humanos , Masculino , MicroRNAs/sangue , MicroRNAs/genética , Pessoa de Meia-Idade
11.
Nanomedicine (Lond) ; 14(19): 2519-2533, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31317822

RESUMO

Aim: To explore the potential therapeutic effect of yttrium oxide nanoparticles (Y2O3 NPs) on fulminant hepatic failure. Materials & methods: RAW264.7 cells and a lipopolysaccharide/D-galactosamine-induced hepatic failure murine model were used to assess the effects of Y2O3 NPs. Results: Y2O3 NPs exhibited anti-inflammatory activity by scavenging cellular reactive oxygen species and dampening reactive oxygen species-mediated NF-κB activation in vitro. A single intraperitoneal administration of Y2O3 NPs (30 mg/kg) enhanced hepatic antioxidant status and reduced oxidative stress and inflammatory response in lipopolysaccharide/galactosamine-induced mice. Y2O3 NPs also attenuated hepatic NF-κB activation, cell apoptosis and liver injury. Conclusion: Y2O3 NP administration could be used as a novel therapeutic strategy for treating fulminant hepatic failure and oxidative stress-related diseases.


Assuntos
Falência Hepática Aguda/tratamento farmacológico , Nanopartículas/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Ítrio/farmacologia , Animais , Antioxidantes/química , Apoptose/efeitos dos fármacos , Galactosamina/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos , Lipopolissacarídeos/toxicidade , Fígado/efeitos dos fármacos , Fígado/patologia , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/patologia , Camundongos , NF-kappa B/genética , Nanopartículas/química , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Ítrio/química
12.
Int J Nanomedicine ; 14: 3297-3309, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190794

RESUMO

Background: Cardiovascular disease (CVD) is the leading cause of mortality all over the world. Vascular stents are used to ameliorate vascular stenosis and recover vascular function. The application of nanotubular coatings has been confirmed to promote endothelial cell (EC) proliferation and function. However, the regulatory mechanisms involved in cellular responses to the nanotubular topography have not been defined. In the present study, a microarray analysis was performed to explore the expression patterns of long noncoding RNAs (lncRNAs) in human coronary artery endothelial cells (HCAECs) that were differentially expressed in response to nitinol-based nanotubular coatings. Materials and methods: First, anodization was performed to synthesize nitinol-based nanotubular coatings. Then, HCAECs were cultured on the samples for 24 h to evaluate cell cytoskeleton organization. Next, total RNA was extracted and synthesized into cRNA, which was hybridized onto the microarray. GO analysis and KEGG pathway analysis were performed to investigate the roles of differentially expressed messenger RNAs (mRNAs). Quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) was performed to validate the expression of randomly selected lncRNAs. Coexpression networks were created to identify the interactions among lncRNAs and the protein-coding genes involved in nanotubular topography-induced biological and molecular pathways. Independent Student's t-test was applied for comparisons between two groups with statistical significance set at p<0.05. Results: 1085 lncRNAs and 227 mRNAs were significantly differentially expressed in the nitinol-based nanotubular coating group. Bioinformatics analysis revealed that extracellular matrix receptor interactions and cell adhesion molecules play critical roles in the sensing of nitinol-based nanotubular coatings by HCAECs. The TATA-binding protein (TBP) and TBP-associated transfactor 1 (TAF1) are important molecules in EC responses to substrate topography. Conclusion: This study suggests that nanotubular substrate topography regulates ECs by differentially expressed lncRNAs involved extracellular matrix receptor interactions and cell adhesion molecules.


Assuntos
Ligas/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Vasos Coronários/citologia , Células Endoteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Nanotubos/química , RNA Longo não Codificante/genética , Proliferação de Células/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Células Endoteliais/efeitos dos fármacos , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Análise em Microsséries , Nanotubos/ultraestrutura , Fenótipo , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição/metabolismo
13.
Transfusion ; 59(5): 1799-1808, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30737804

RESUMO

BACKGROUND: Cryopreservation in dimethyl sulfoxide and storage at -80 °C extends the shelf life of platelets to at least 2 years, allowing greater availability in rural and military areas. While cryopreserved platelets (CPPs) have been extensively characterized for coagulation and thrombin generation, reports on the mechanism of adverse reactions to CPPs transfusion are scarce. Here, we tested the hypothesis that CPPs facilitate phagocytosis by Kupffer cells and subsequently promote the inflammatory response in Kupffer cells. STUDY DESIGN AND METHODS: P-selectin expression, glycoprotein Ibα clustering and phosphatidylserine (PS) surface exposure on platelets stored at 22 °C, 4 °C and - 80 °C for 3 days were examined by flow cytometry. The phagocytosis of mepacrine-labeled platelets coincubated with THP-1 cells was examined by flow cytometry and confocal microscopy, and the release of cytokines from THP-1 cells was measured by enzyme-linked immunosorbent assay. RESULTS: CPPs showed a marked enhancement of exposed PS but dramatically reduced glycoprotein Ibα expression and clustering compared with platelets stored at 4 °C. Activation of THP-1 cells was stronger by CPPs than by platelets stored at 22 °C and 4 °C. CPP interference tests using annexin V and anti-P-selectin showed that CPPs induced increases in PS- and P-selectin-mediated phagocytosis, as well as secretion of the proinflammatory cytokine tumor necrosis factor-α, and interleukins IL-1ß and IL-6, but a decrease in transforming growth factor-ß production in THP-1 cells. Surface-exposed PS was more effective than P-selectin for the activation of THP-1 cells. CONCLUSION: CPPs triggered PS and P-selectin-mediated phagocytosis by macrophages and stimulated the inflammatory response of macrophages.


Assuntos
Plaquetas/citologia , Plaquetas/metabolismo , Criopreservação/métodos , Inflamação/metabolismo , Selectina-P/metabolismo , Fosfatidilserinas/metabolismo , Linhagem Celular , Humanos , Macrófagos/citologia , Macrófagos/metabolismo , Fagocitose/fisiologia , Complexo Glicoproteico GPIb-IX de Plaquetas/química , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Quinacrina
14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 40(4): 539-542, 2018 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-30193609

RESUMO

Objective To preliminarily validate the clinical usability of the ameliorated Kawashima Itch Scale(Xie-Kawashima Itch Scale) among adult pruritic patients on maintenance hemodialysis. Methods Xie-Kawashima Itch Scale was developed on the basis of Kawashima Itch Scale. Patients were asked to record their pruritus condition according to Xie-Kawashima Itch Scale or visual analogue scale(VAS) during daytime and night for two weeks. The record at the second week was used for analyzing the correlation between Xie-Kawashima Itch Scale and VAS. Results Totally 134 patients were enrolled in this study,among whom 128 entered the final analysis. Xie-Kawashima Itch Scale was positively correlated with VAS(rs=0.832,95% CI=0.810-0.851,P<0.01 for daytime record;and rs=0.848,95% CI=0.828-0.865,P<0.01 for night record). Subgroup analysis also showed similar correlations between different age groups and among different gender groups. Conclusion Xie-Kawashima Itch Scale has good correlation with VAS in patients on hemodialysis,without being affected by age or gender. Thus,it can be a useful tool for the assessment of pruritus in clinical practice and research.


Assuntos
Medição da Dor , Prurido/diagnóstico , Escala Visual Analógica , Adulto , Humanos , Diálise Renal
15.
Curr Med Sci ; 38(2): 212-221, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30074178

RESUMO

The objectives of this study were to investigate the effects of the CRISPR/Cas9 system mediated by the HPV pseudotype virus on SiHa cytobiology behavior by cutting the HPV16 E6 gene selectively and to explore the role of this system in the treatment of cervical cancer. After designing specific gRNA sequences targeting HPV16 E6, generating hCas9-EGFP and E6-gRNA-RFP plasmids, and preparing the pseudovirus of HPV16 carrying E6-gRNA and Cas9 plasmids, we determined the titer of the pseudotype virus using the TCID50 method. We obtained the pseudotype virus of HPV16 carrying E6-gRNA and Cas9 plasmids to transfect cervical cancer SiHa cells. Experimental subjects were divided into control group, empty virus group, E6-gRNA transfected group, Cas9 transfected group and Cas9+E6-gRNA transfected group. The molecular size of the cutting sequence was detected using the T7E1 enzyme digestion method and agarose gel electrophoresis, and the cleavage function of CRISPR/Cas9 on the E6 gene was determined at the same time. RT-PCR and Western blotting were performed to detect the mRNA and protein expression levels of E6 in all the groups; the Transwell cell migration assay was performed to detect the cell migration ability and metastasis in all groups. Heterotopic transplantation tumors were incorporated into mice and were used to investigate the effects of the CRISPR/Cas9 system mediated by the HPV pseudovirus on the tumorigenic ability of SiHa cells by selectively cutting HPV16 E6. The HPV16 pseudotype virus carrying E6-gRNA and Cas9 plasmids could successfully infect SiHa cells, and there were two cutting zones in the Cas9+E6-gRNA transfected group. However, the empty virus group, E6-gRNA transfected group and Cas9 transfected group had no corresponding zone. Compared with those in the control group, the empty virus group, E6-gRNA transfected group and Cas9 transfected group, the mRNA and protein expression levels of E6 in SiHa cells were downregulated in the Cas9+E6-gRNA transfected group (P<0.01). In addition, the proliferation and migration abilities of SiHa cells were significantly inhibited (P<0.01). There were no significant differences among the other groups. In contrast to the control group, the HPV pseudotype virus carrying E6-gRNA and Cas9 plasmids could significantly delay the growth of tumor cells of the ectopic tumor transplantation model (P<0.01). The CRISPR/Cas9 system mediated by the HPV pseudotype virus to knockout E6 gene expression exhibited a clear inhibitory effect on the biological function of SiHa cells, which indicated that knocking out the E6 gene using the CRISPR/Cas9 system mediated by the HPV pseudotype virus had a potential effect of eliminating HPV infection and inhibiting the growth of HPV-related tumors. Taken together, these findings provide insight into a new treatment strategy for the prevention and treatment of hr-HPV infected disease, particularly in HPV-related tumors.


Assuntos
Papillomavirus Humano 16/metabolismo , Proteínas Oncogênicas Virais/genética , Proteínas Repressoras/genética , Animais , Sistemas CRISPR-Cas/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Proteínas Oncogênicas Virais/metabolismo , Plasmídeos/metabolismo , RNA Guia/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Repressoras/metabolismo
16.
J Trauma Acute Care Surg ; 85(2): 327-333, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29787551

RESUMO

BACKGROUND: Platelets are essential for primary hemostasis and also play an important role in inflammatory reactions. The hemostatic property of cryopreserved platelets (CPPs) has been confirmed in the treatment of bleeding casualties, but inflammatory injury induced by CPP transfusion is relatively unclear. We aim to investigate the effects of CPP transfusion on inflammatory organ injury in mice after hemorrhage. METHODS: Mice were subjected to a volume-controlled hemorrhage over 1 hour, and then were transfused with fresh platelets (FPs), Liquid-stored platelets (LPPs), CPPs, or fresh frozen plasma (FFP, control). At 6 hours posttransfusion, mice were sacrificed, and blood and tissues were sampled. Tissue sections were examined histologically and by immunohistochemical staining of neutrophils and macrophages. Plasma alanine aminotransferase, hepatic myeloperoxidase activity and inflammatory cytokine levels were measured. RESULTS: Transfusion of stored platelets (LPPs and CPPs) caused more serious histological injury in liver and lung compared with FPs and FFP (p < 0.05). However, kidney histological injury was similar among groups. Significantly higher numbers of Ly-6G-positive neutrophils were detected in liver and of F4/80-positive macrophages in liver and lung of mice transfused with LPPs or CPPs compared with FPs or FFP (p < 0.05). Transfusion of CPPs caused the most severe inflammatory liver injury, as reflected by alanine aminotransferase levels, hepatic macrophage infiltration, and hepatic myeloperoxidase activity and inflammatory cytokine levels (macrophage inflammatory protein-2, tumor necrosis factor-α, and interleukin-1ß). CONCLUSION: Cryopreserved platelet transfusion is more likely to aggravate hemorrhage-induced liver and lung injury by activating macrophage and facilitating neutrophil infiltration into hepatic tissues.


Assuntos
Criopreservação , Hemorragia/terapia , Insuficiência de Múltiplos Órgãos/etiologia , Plasma , Transfusão de Plaquetas/efeitos adversos , Alanina Transaminase/sangue , Animais , Citocinas/sangue , Modelos Animais de Doenças , Hemorragia/complicações , Inflamação/patologia , Fígado/fisiopatologia , Pulmão/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C
17.
J Surg Res ; 226: 150-156, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29661281

RESUMO

BACKGROUND: Uncontrolled hemorrhage (UH) remains the most common cause of death on the battlefield. This study examined the pathophysiological characteristics of UH in rats acutely exposed to high altitude. MATERIAL AND METHODS: Rats raised at sea level were randomly divided into two groups. Rats in the high-altitude group were exposed to hypobaric hypoxia in a hypobaric chamber (simulating 4000 m above sea level) for 2 d and then were performed a hemorrhagic shock protocol in the hypobaric chamber. Rats that underwent the same hemorrhage procedure at sea level were used as control. Anesthetized rats were bled to maintain their mean arterial pressure at 45 mmHg for 1 h. The distal quarter of the tail was amputated to allow free blood loss. After 1 h, the tail cut was ligated to induce hemostasis. mean arterial pressure, acid-base balance, blood loss, and survival were recorded. Rats were killed, and tissues were obtained for histological analysis. RESULTS: Rats in the high-altitude group suffered less uncontrolled blood loss, more severe acidosis (lower pH and base excess), and inferior tissue oxygen supply (lower oxygen saturation and higher arterial lactate concentration) during the hemorrhage periods compared with the control group. Survival rates were significantly lower in the high-altitude group than those in the control group (P < 0.05), which was consistent with the results of pathological tissue injury. CONCLUSIONS: In this rat model of hemorrhagic shock, acute high-altitude exposure resulted in decreased UH but more serious hemorrhagic shock injuries than that at sea level.


Assuntos
Altitude , Hipóxia/mortalidade , Choque Hemorrágico/mortalidade , Lesões Relacionadas à Guerra/mortalidade , Animais , Pressão Sanguínea , Modelos Animais de Doenças , Humanos , Hipóxia/etiologia , Hipóxia/patologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Choque Hemorrágico/etiologia , Choque Hemorrágico/patologia , Taxa de Sobrevida , Lesões Relacionadas à Guerra/complicações , Lesões Relacionadas à Guerra/patologia
18.
Mol Med Rep ; 17(2): 2229-2238, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29207048

RESUMO

The present study investigated the mechanism underlying Toll-like receptor 4 (TLR4)-mediated stimulation of hypoxia-inducible factor-1α (HIF-1α) activity and its association with reactive oxygen species (ROS) in cervical cancer cells. SiHa cells were cultured and randomized to control, lipopolysaccharide (LPS), methyl-ß-cyclodextrin (MßCD)+LPS, ammonium pyrrolidinedithiocarbamate (PDTC)+LPS, ST2825+LPS and small interfering (si) RNA TLR4+LPS treatment groups. Cell proliferation was quantified using an MTT assay, cell cloning was performed using soft agar colony formation and HIF-1α expression was detected by immunocytochemical staining and western blot analyses. Dichloro-dihydro-fluorescein diacetate and lucigenin luminescence assays were used to detect alterations in ROS and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase content, respectively. Co-localization of TLR4 and HIF-1α was detected by immunofluorescence staining and observed using fluorescence microscopy. Compared with the control group, cell proliferation was enhanced in the LPS-treated group and was not altered in the PDTC+LPS treatment group. Cell proliferation was reduced in all other treatment groups (P<0.05). Compared with the LPS group, cell proliferation decreased in all other groups. Compared with the PDTC+LPS treatment group, cell proliferation significantly decreased when LPS was co-administered with ST2825, siTLR4 and MßCD (P<0.01). Treatment with MßCD+LPS exhibited an increased inhibitory effect on cell activity and proliferation. Compared with the control group, HIF-1α expression was enhanced following treatment with LPS, although it decreased when LPS was co-administered with ST2825, siTLR4 and MßCD (P<0.05). HIF-1α expression decreased following treatment with ST2825, siTLR4, MßCD and PDTC+LPS, compared with treatment with LPS alone. Compared with the PDTC+LPS group, HIF-1α activity decreased when LPS was co-administered with ST2825, siTLR4 and MßCD. NADPH oxidase and ROS levels increased in cells treated with LPS, compared with the control group, at 24 and 12 h following treatment, respectively, and decreased at 12 h when LPS was co-administered with ST2825, siTLR4 and MßCD. There was no difference between the LPS and PDTC+LPS groups with respect to NADPH and ROS levels. Compared with the PDTC+LPS group, NADPH oxidase activity and ROS content decreased when LPS was co-administered with ST2825, siTLR4 and MßCD. NADPH oxidase activity and ROS content were lowest in the MßCD+LPS treatment group, and immunofluorescent staining demonstrated that TLR4 was localized to the cell surface and HIF-1α was primarily localized to the cytoplasm. TLR4 was co-expressed with HIF-1α in cervical cancer cells. The results of the present study suggested that TLR4 signaling primarily promoted HIF-1α activity via activation of lipid rafts/NADPH oxidase redox signaling and may be associated with the initiation and progression of cervical cancer. This promoting effect was stronger in TLR4/lipid rafts/NADPH oxidase pathway than that in TLR4-NF-κB signaling pathway. Therefore, the TLR4/lipid raft-associated redox signal may be a target for therapeutic intervention to prevent the growth of cervical cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptor 4 Toll-Like/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , NADPH Oxidases/metabolismo , Ligação Proteica , Transporte Proteico , Ensaio Tumoral de Célula-Tronco
19.
Biomaterials ; 144: 30-41, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28820966

RESUMO

Sepsis-associated acute liver injury contributes to the pathogenesis of multiple organ dysfunction syndrome and is associated with increased mortality. Currently, no specific therapeutics for sepsis-associated liver injury are available. With excess levels of reactive oxygen species (ROS) being implicated as key players in sepsis-induced liver injury, we hypothesize that ROS-responsive nanoparticles (NPs) formed via the self-assembly of diblock copolymers of poly(ethylene glycol) (PEG) and poly(propylene sulfide) (PPS) may function as an effective drug delivery system for alleviating sepsis-induced liver injury by preferentially releasing drug molecules at the disease site. However, there are no reports available on the biocompatibility and effect of PEG-b-PPS-NPs in vivo. Herein, this platform was tested for delivering the promising antioxidant therapeutic molecule melatonin (Mel), which currently has limited therapeutic efficacy because of its poor pharmacokinetic properties. The mPEG-b-PPS-NPs efficiently encapsulated Mel using the oil-in-water emulsion technique and provided sustained, on-demand release that was modulated in vitro by the hydrogen peroxide concentration. Animal studies using a mouse model of sepsis-induced acute liver injury revealed that Mel-loaded mPEG-b-PPS-NPs are biocompatible and much more efficacious than an equivalent amount of free drug in attenuating oxidative stress, the inflammatory response, and subsequent liver injury. Accordingly, this work indicates that mPEG-b-PPS-NPs show potential as an ROS-mediated on-demand drug delivery system for improving Mel bioavailability and treating oxidative stress-associated diseases such as sepsis-induced acute liver injury.


Assuntos
Antioxidantes/administração & dosagem , Preparações de Ação Retardada/metabolismo , Falência Hepática Aguda/tratamento farmacológico , Melatonina/administração & dosagem , Nanopartículas/metabolismo , Polietilenoglicóis/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sulfetos/metabolismo , Animais , Antioxidantes/uso terapêutico , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/metabolismo , Masculino , Melatonina/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Sepse/complicações , Sepse/metabolismo
20.
J Surg Res ; 216: 73-79, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28807216

RESUMO

BACKGROUND: Oxidative stress induced by hemorrhagic shock (HS) is known to initiate a systemic inflammatory response, which leads to subsequent acute lung injury. This study is aimed to assess the efficacy of exendin-4 (Ex-4) in attenuating lung injury in a rat model of HS and resuscitation (HS/R). METHODS: HS was induced in sodium pentobarbital-anesthetized adult male Wistar rats by withdrawing blood to maintain a mean arterial pressure of 30-35 mm Hg for 50 min. Then, the animals received Ex-4 (5 µg/kg) or vehicle (saline) intravenously and were resuscitated with a volume of normal saline 1.5 times that of the shed blood volume. Mean arterial pressure was measured throughout the experiment, and acid-base status, oxidative stress, inflammation, and lung injury were evaluated at 2 h after resuscitation. RESULTS: Ex-4 infusion reduced the methemoglobin content, the malondialdehyde content, the myeloperoxidase activity, and the expression of tumor necrosis factor-α and interleukin-6 in the lungs. The histologic injury was also markedly decreased in the Ex-4 group compared with the vehicle group. CONCLUSIONS: Ex-4 ameliorates the oxidative stress, inflammatory response, and subsequent acute lung injury occurring after HS/R. Although future studies are required to elucidate the underlying mechanism, our results indicate that Ex-4 infusion may be a promising strategy for improving lung injury in the treatment of HS.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Antioxidantes/uso terapêutico , Peptídeos/uso terapêutico , Ressuscitação/métodos , Choque Hemorrágico/terapia , Peçonhas/uso terapêutico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Terapia Combinada , Exenatida , Hidratação , Infusões Intravenosas , Masculino , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar , Choque Hemorrágico/complicações , Resultado do Tratamento , Peçonhas/farmacologia
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