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1.
Chem Pharm Bull (Tokyo) ; 72(2): 186-189, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38346722

RESUMO

As a part of our continuing exploration to discover new potential promising fungicide candidates, eighteen sulfonate derivatives (3a-3r) containing a kakuol moiety were designed and synthesized. Synthetic sulfonate derivatives were tested comprehensively for antifungal activities against four plant pathogenic fungi (Botrytis (B.) cinerea, Valsa (V.) mali, Fusarium (F.) graminearum, Sclerotinia (S.) sclerotiorum), and their structure activity relationships were summarized. Especially, derivatives 3i and 3j exhibited remarkable activity against V. mali, with the inhibition rates of 99.8 and 100%, which were slightly superior to that of carbendazim (98.9%), a reference fungicide. Moreover, derivatives 3a, 3k and 3q possess the broader antifungal spectrum against three tested plant pathogenic fungi with inhibition rates over 60%. Structure-activity relationship (SAR) analysis indicated that the introduction of 2-F or 3-F into the benzene ring would give rise to a remarkable increase of the antifungal activity against V. mali.


Assuntos
Ascomicetos , Benzodioxóis , Fungicidas Industriais , Propiofenonas , Antifúngicos/química , Fungicidas Industriais/farmacologia , Estrutura Molecular , Relação Estrutura-Atividade , Plantas
2.
RSC Adv ; 13(38): 26324-26329, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37671352

RESUMO

A novel tetranuclear Cu(ii) complex (TNC) was successfully synthesized and characterized by X-ray single crystal diffraction. The interaction of the complex with calf thymus DNA (CT-DNA) has been studied by UV-vis absorption titration, fluorescence technology and molecular docking. The results indicated that TNC could bind to the DNA through an intercalative mode. The agarose gel electrophoresis experiment showed that TNC could cleave supercoiled plasmid DNA into linear DNA. The anticancer activity of TNC was tested on four cancer cell lines: MCF7, A549, 4T1 and HepG2. The results indicated that TNC shown significant activity against all of above cell lines.

3.
Pharm Dev Technol ; 27(10): 1049-1056, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36398607

RESUMO

Recent findings revealed that low-concentration paclitaxel(DTX) could enhance cytotoxicity by upregulating p53 expression in lung cancer cell lines. So, co-delivery of DTX and RFP-p53 gene with PEA nanoparticles (NPs) was studied. The prepared DTX loaded PEA NPs (PEA/DTX) were characterized by particle size distribution, morphology, zeta potential, and crystallography and cytotoxicity. Results showed that the PEA/DTX NPs had a mall particle size (≤100 nm), moderate zeta potential (≥40 mV) and drug loading of 9.0%, DTX was released from PEA/DTX NPs in an extended period in vitro. More important, agarose gel electrophoresis showed that PEA/DTX cationic NPs were able to completely bind RFP-p53 gene with mean particles size and zeta potential. Studies on cellular uptake of (PEA/DTX)/RFP-p53 NPs demonstrated that both drug and gene were effectively taken up by A549 tumor cells. It was found that intravenous injection of (PEA/DTX)/RFP-p53 NPs efficiently inhibited growth of subcutaneous A549 carcinoma in vivo (p < 0.05) and was significantly less side effect than that of mice treated with the other groups. Therefore, the (PEA/DTX)/RFP-p53 NPs might be a promising candidate for A549 cancer therapy.


Assuntos
Nanopartículas , Polietilenoimina , Camundongos , Animais , Docetaxel/farmacologia , Genes p53 , Proteína Supressora de Tumor p53/genética , Taxoides , Nanopartículas/química
4.
Chem Commun (Camb) ; 58(61): 8536-8539, 2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35811481

RESUMO

Herein, we designed a new nanoplatform for combined PDT/PTT/CDT through simultaneously self-supplying H2O2 and depleting GSH using one single laser irradiation. The nanoplatform was capable of generating multiple reactive oxygen species (ROS), such as 1O2, O2-˙ and ˙OH, resulting in cell death. Moreover, the nanoplatform demonstrated low dark toxicity, high phototoxicity and better biosafety. In vivo animal experiments showed that the tumor growth was efficiently inhibited.


Assuntos
Neoplasias , Fotoquimioterapia , Animais , Linhagem Celular Tumoral , Peróxido de Hidrogênio/farmacologia , Neoplasias/tratamento farmacológico , Estresse Oxidativo , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo
5.
Micromachines (Basel) ; 12(11)2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34832732

RESUMO

In this paper, a tunable absorber composed of asymmetric grating based on a graphene-dielectric-metal structure is proposed. The absorption of the absorber can be modified from 99.99% to 61.73% in the near-infrared by varying the Fermi energy of graphene, and the absorption wavelength can be tuned by varying the grating period. Furthermore, the influence of other geometrical parameters, the incident angle, and polarization are analyzed in detail by a finite-difference time-domain simulation. The graphene absorbers proposed in this paper have potential applications in the fields of stealth, sense, and photoelectric conversion. When the absorber that we propose is used as a gas sensor, the sensitivity of 200 nm/RIU with FOM can reach up to 159 RIU-1.

6.
Opt Express ; 28(17): 25073-25084, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32907037

RESUMO

High-performance omnidirectional transmissive chromatic polarizers based on a one-dimensional dielectric-metal-dielectric subwavelength grating structure are proposed. The incident angle-insensitive properties, azimuthal angle-insensitive properties and polarization features are investigated thoroughly to realize the proposed omnidirectional transmissive chromatic polarizers. The color difference at different angles for the proposed yellow polarizers is less than 0.9746, and the extinction ratio at different angles for the proposed cyan polarizers exceeds 26. Analysis of the power density profiles for the transverse electric (TE) and transverse magnetic (TM) polarizations show that surface plasmon resonance and high refractive index contrast properties lead to excellent polarization features and high angular tolerance.

7.
Dalton Trans ; 49(34): 11851-11858, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32700693

RESUMO

A bimetallic Cu(ii) complex as a novel antitumor chemodynamic therapy agent with glutathione (GSH) depletion properties is successfully synthesized and well characterized. In tumor cells, the Cu2+ ions of the complex are reduced to Cu+ ions by GSH and then catalyzed by the overexpressed H2O2 to generate highly cytotoxic hydroxyl radicals (˙OH) that kill cancer cells. The complex is quickly taken up by cancer cells and distributed in multiple organelles including mitochondria and the nucleus. The complex demonstrates good cytotoxicity toward various cancer cell lines. However, its toxicity toward normal cells is significantly lower than that toward cancer cells due to the limited expression of H2O2. In addition, the complex could arrest the cell cycle of the G0/G1 phase, thereby inducing apoptosis rather than necrosis.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cobre/química , Glutationa/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Fase de Repouso do Ciclo Celular/efeitos dos fármacos
8.
Chem Commun (Camb) ; 55(86): 12956-12959, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31602444

RESUMO

A bimetallic complex, containing Mn(ii) and Cu(ii) moieties, was synthesized for chemodynamic therapy (CDT) of cancer. The complex was capable of generating a hydroxyl radical (˙OH) via a Fenton-like reaction involving a Mn complex, and simultaneously depleting glutathione via a Cu complex induced oxidative reaction, thereby enhancing the efficiency of CDT.


Assuntos
Complexos de Coordenação/química , Cobre/química , Glutationa/metabolismo , Manganês/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Glutationa/química , Humanos , Radical Hidroxila/metabolismo , Azul de Metileno/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fotoquimioterapia
9.
Mol Med Rep ; 18(5): 4523-4529, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30221740

RESUMO

Increasing evidence has demonstrated that complement activation is required for ischemia­reperfusion injury (IRI)­induced hepatic damage, and cobra venom factor (CVF) can deplete the complement components. The aim of the current study was to investigate the effect and intrinsic mechanism of CVF pretreatment on IRI­induced acute hepatic injury in rats. Acute hepatic injury in rats was induced by bone fracture to simulate trauma, followed by hemorrhage for 90 min, and then the rats were resuscitated for a period of 20 min of reperfusion. The survival times under different CVF treatment doses and schedules for rats with IRI were evaluated. Hepatic tissues and serum samples were analyzed for acute hepatic injury, complement activation, inflammatory mediator release and apoptosis at predetermined times and compared between the IRI group and the CVF pretreatment + IRI groups. Compared to the rats with IRI alone, the survival times were significantly improved among rats with IRI receiving a high­dose or low­dose CVF pretreatment (all P<0.01). Upon histological examination, severe hepatic damage was observed in the rats with IRI, accompanied by liver function deterioration, complement and membrane attack complex activation, inflammatory mediator release and hepatic cell apoptosis. CVF pretreatment significantly attenuated the hepatic injury through depletion of anaphylatoxic C5a and membrane attack complex C5b­9 activation, and subsequent inhibition of inflammatory mediator release and hepatic cell apoptosis (all P<0.05). The results indicated that CVF pretreatment ameliorates IRI­induced acute hepatic injury. However, further studies are required to determine whether this therapy could be a potential agent for the treatment of IRI injuries in clinical settings.


Assuntos
Venenos Elapídicos/administração & dosagem , Inflamação/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Ativação do Complemento/efeitos dos fármacos , Complemento C5a/efeitos dos fármacos , Complemento C5a/metabolismo , Complexo de Ataque à Membrana do Sistema Complemento/efeitos dos fármacos , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Venenos Elapídicos/química , Fraturas Ósseas/complicações , Fraturas Ósseas/fisiopatologia , Humanos , Inflamação/complicações , Inflamação/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/lesões , Fígado/fisiopatologia , Hepatopatias/complicações , Ratos , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/fisiopatologia
10.
Int J Mol Med ; 39(5): 1111-1118, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28350048

RESUMO

Silybin is one of the main flavonoids produced by milk thistle, which has been used in the treatment of liver diseases. In this study, we examined the protective effects and possible mechanisms of action of silybin in lipopolysaccharide (LPS)­induced lung injury and inflammation. Pre-treatment of mice with silybin significantly inhibited LPS-induced airway inflammatory cell recruitment, including macrophages, T cells and neutrophils. The production of cytokines, such as interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in bronchoalveolar fluid and serum was also decreased following treatment with silybin. Elevated cytokine mRNA levels induced by LPS in lung tissue were all suppressed by silybin and lung histological alterations were also improved. In addition, experiments using cells indicated that silybin significantly decreased the mRNA levels and secretion of IL-1ß and TNF-α in THP-1 cells. Moreover, the mechanisms responsible for these effects were attributed to the inhibitory effect of silybin on nuclear factor-κB (NF-κB) signaling and NLR family pyrin domain containing 3 (NLRP3) inflammasome activation. The data form our study thus support the utility of silybin as a potential medicine for the treatment of acute lung injury­associated inflammation and pathological changes. Silybin exerts protective effects against lung injury by regulating NF-κB signaling and the NLRP3 inflammasome activation.


Assuntos
Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Lipopolissacarídeos/efeitos adversos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais/efeitos dos fármacos , Silimarina/farmacologia , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Animais , Linhagem Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Inflamassomos/metabolismo , Mediadores da Inflamação/metabolismo , Camundongos , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Silibina
11.
Zhongguo Zhen Jiu ; 36(4): 347-50, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-27352488

RESUMO

OBJECTIVE: To observe the clinical efficacy of deep acupuncture at Lianquan (CV 23) and Yifeng (TE 17) combined with swallowing training for post-stroke dysphagia. METHODS: Sixty cases of post-stroke dys phagia were randomly divided into an observation group and a control group, 30 cases in each one. Patients in the observation group, based on the regular acupuncture treatment, were treated with deep acupuncture at Lianquan (CV 23) and Yifeng (TE 17), once a day, 30 min per treatment; also swallowing training was combined, twice a day, 20 min per treatment. Patients in the control group were treated with swallowing training. All the patients were treated with regular treatment of stroke. Six days of treatment were taken as one session, and totally 3 sessions were given with an interval of one day between sessions. The video fluoroscopic swallowing study (VFSS) dysphagia evaluation scale and Watian water swallow test (WWST) were evaluated before and after treatment also the clinical efficacy and the recovery time of two groups were compared. RESULTS: After treatment, the VFSS score in the observation group was significantly superior to that in the control group (P < 0.01); the WWST in the observation group was significantly superior to that in the control group (P < 0.01). The cured rate was 70.0% (21/30) in the observation group, which was significantly superior to 43.3% (13/30) in the control group (P < 0.01); the total effective rate was 86.7% (26/30) in the observation group, which was significantly superior to 66.7% (20/30) in the control group (both P < 0.01). The clinical recovery time in the observation group was significantly shorter than that in the control group (P < 0.01). CONCLUSION: Deep acupuncture at Lianquan (CV 23) and Yifeng (TE 17) combined with swallowing training could effectively improve post-stroke swallow function.


Assuntos
Terapia por Acupuntura , Transtornos de Deglutição/terapia , Acidente Vascular Cerebral/complicações , Pontos de Acupuntura , Idoso , Terapia Combinada , Deglutição , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/reabilitação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
12.
PLoS One ; 11(1): e0147380, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26809128

RESUMO

BACKGROUND: Histone deacetylase 2 (HDAC2) is a class I histone deacetylase family member that plays a critical role in suppressing inflammatory gene expression in the airways, lung parenchyma, and alveolar macrophages in patients with chronic obstructive pulmonary disease (COPD). However, the expression of HDAC2 in peripheral blood monocytes (PBMCs), nuclear factor kappa B (NF-κB) p65, and serum inflammatory cytokine levels in COPD patients, smokers, and non-smokers remains unclear. METHODS: PBMCs were obtained from COPD patients, healthy smokers, and healthy nonsmokers. The HDAC2 and NF-κB p65 expression were quantified by Western Blot. HDAC activity was assessed by an HDAC fluorometric immunoprecipitation activity assay kit. Serum tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) levels were measured by ELISA. RESULTS: HDAC2 expression and HDAC activity were decreased in PBMCs in COPD patients compared with smokers and non-smokers. Increased NF-κB p65 expression, serum TNF-α and IL-8 levels were observed in COPD patients compared with nonsmokers. The FEV1%pred was positively correlated with HDAC2 expression and HDAC activity in COPD patients. Smokers had decreased HDAC activity, increased NF-κB p65 expression and serum TNF-α compared with nonsmokers. CONCLUSIONS: HDAC2 expression was decreased in PBMCs of COPD patients and was correlated with disease severity. The reduction of HDAC2 expression not only directly enhances the expression of inflammatory genes, but may account for the activation of NF-κB mediated inflammation. Decreased HDAC2 may serve as a potential biomarker of COPD and predict the decline of lung function.


Assuntos
Histona Desacetilase 2/metabolismo , Monócitos/enzimologia , Doença Pulmonar Obstrutiva Crônica/enzimologia , Idoso , Citocinas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/sangue , Fator de Transcrição RelA/metabolismo
13.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 28(3): 277-80, 2016 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-29919984

RESUMO

Objective: To compare the clinical effects between continuous renal replacement therapy (CRRT) and intermittent haemodialysis (IHD) for the treatment of sepsis-induced acute kidney injury (AKI). Methods: A prospective study was conducted. Seventy-three patients with sepsis-induced AKI admitted to the intensive care units (ICUs) of Tianjin Hospital and Tianjin First Center Hospital from January to December in 2014 were enrolled. They were randomly divided into two groups: CRRT group (n = 35) and IHD group (n = 38). Data were recorded for the patients in two groups before treatment, including acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, mean arterial pressure (MAP), urine volume, and the levels of C-reactive protein (CRP) and serum creatinine (SCr) before and 1 week after treatment, the time of recovery of urine volume, the length of ICU stay, the duration of organ support, and the incidence of cardiovascular events. Results: There was no statistically significant difference in APACHE Ⅱ scores (21.63±2.46 vs. 21.34±2.46), MAP [mmHg (1 mmHg = 0.133 kPa): 71.26±10.70 vs. 75.74±15.17], urine volume (mL: 404.00±79.13 vs. 438.97±87.17), CRP (mg/L: 100.94±14.73 vs. 95.17±27.03), and SCr (µmol/L: 394.02± 50.26 vs. 390.47±54.42) before treatment between CRRT group and IHD group (all P > 0.05). One week after treatment, compared to the IHD group, CRRT could dramatically reduce the levels of CRP (mg/L: 41.05±10.15 vs. 60.21±14.78, t = 6.401, P < 0.001), SCr (µmol/L: 185.97±65.48 vs. 232.02±71.93, t = 2.862, P = 0.006), urine output recovery time (days: 7.94±3.06 vs. 11.08±3.71, t = 3.923, P < 0.001), the length of ICU stay (days: 9.54±3.39 vs. 13.42±3.89, t = 4.521, P < 0.001), organ support time (days: 3.23±2.70 vs. 6.34±3.36, t = 4.343, P < 0.001), and the incidence of cardiovascular events [23.53% (8/35) vs. 39.47% (15/38), χ2 = 5.509, P = 0.025]. Conclusion: Compared to IHD, CRRT can more efficiently help patients with sepsis-induced AKI in removing excessive water, metabolic waste, and lower the levels of pro-inflammatory cytokines, maintain homeostasis of the internal environment, lower the adverse effects on cardiovascular system, so that it significantly improve the prognosis of patients, shorten the time of organ support and the length of ICU stay.


Assuntos
Injúria Renal Aguda/terapia , Diálise Renal , Terapia de Substituição Renal , APACHE , Injúria Renal Aguda/etiologia , Citocinas/metabolismo , Humanos , Unidades de Terapia Intensiva , Prognóstico , Estudos Prospectivos , Sepse/complicações , Resultado do Tratamento
14.
Yao Xue Xue Bao ; 50(8): 986-92, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26668998

RESUMO

The aim of this study is to investigate the anti-inflammatory effect of the adenosine derivative N6-(3-hydroxylaniline) adenosine (WS070117M1) on cigarette smoke plus LPS (lipopolysaccharide)-induced chronic obstructive pulmonary disease (COPD) in mice and its mechanism. COPD model was established by exposing male BALB/c mice to cigarette smoke and challenged with LPS inhalation. Supernatants of bronchoalveolar lavage fluid (BALF) were harvested and IL-1ß, IL-6, IL-8 and TGF-ß1 levels were measured by ELISA (enzyme-linked immunesorbent assay). The number of total white blood cells and neutrophils in bronchoalveolar lavage fluid was counted separately. Lung tissue was stained with Mayer 's hematoxylin and eosin for histopathologic examination. pAMPKa protein expression and distribution of lung tissue were analyzed by immunohistochemistry method. In vitro, levels of AMPKα phosphorylation in phorbol-12- myristate-13-acetate (PMA) differentiated THP-1 cells was detected by immunohistochemistry, IL-8 level in supernatants of cigarette smoke condensate stimulating PMA differentiated THP-1 cells was measured by ELISA. The results showed that WS070117M1 treatment significantly activated AMPKa in the lung tissue. It also resulted in down regulation of IL-1ß, IL-6, IL-8 and TGF-ß1 levels in bronchoalveolar lavage fluid and IL-8 level in cigarette smoke condensate stimulating PMA differentiated THP-1 cells. In addition, WS070117M1 could inhibit the recruitment of total white blood cells and neutrophils. These results suggest that WS070117M1 may alleviate the airway inflammation by activating AMPK in the lung tissue.


Assuntos
Adenosina/análogos & derivados , Inflamação/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Líquido da Lavagem Broncoalveolar , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Contagem de Leucócitos , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/citologia , Fumaça/efeitos adversos , Fator de Crescimento Transformador beta1/metabolismo
15.
Korean J Physiol Pharmacol ; 19(6): 491-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26557015

RESUMO

Traumatic brain injury (TBI) is a major cause of mortality and long-term disability, which can decrease quality of life. In spite of numerous studies suggesting that Epigallocatechin-3-gallate (EGCG) has been used as a therapeutic agent for a broad range of disorders, the effect of EGCG on TBI remains unknown. In this study, a weight drop model was established to evaluate the therapeutic potential of EGCG on TBI. Rats were administered with 100 mg/kg EGCG or PBS intraperitoneally. At different times following trauma, rats were sacrificed for analysis. It was found that EGCG (100 mg/kg, i.p.) treatment significantly reduced brain water content and vascular permeability at 12, 24, 48, 72 hour after TBI. Real-time PCR results revealed that EGCG inhibited TBI-induced IL-1ß and TNF-α mRNA expression. Importantly, CD68 mRNA expression decreasing in the brain suggested that EGCG inhibited microglia activation. Western blotting and immunohistochemistry results showed that administering of EGCG significantly inhibited the levels of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression. TBI-induced oxidative stress was remarkably impaired by EGCG treatment, which elevated the activities of SOD and GSH-PX. Conversely, EGCG significantly reduced the contents of MDA after TBI. In addition, EGCG decreased TBI-induced NADPH oxidase activation through inhibition of p47(phox) translocation from cytoplasm to plasma membrane. These data demonstrate that EGCG treatment may be an effective therapeutic strategy for TBI and the underlying mechanism involves inhibition of oxidative stress.

16.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 27(8): 677-81, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26255018

RESUMO

OBJECTIVE: To observe whether lipopolysaccharide ( LPS ) derived from Escherichia coli ( E.coli ) can induce apoptosis of murine platelets in vitro. METHODS: Washed platelet suspension was prepared and adjusted to the final concentration of 3×10(8)/mL. According to the difference in stimulants, samples were divided into control group ( non-calcium Tyrode buffer ), thrombin-treated group ( 1 U/mL final concentration and non-calcium TB ) and LPS in different concentrations treated groups ( 1, 10 and 100 µg/mL final concentration respectively and non-calcium TB ). To each specimental group corresponding stimulus was added and incubated 30 minutes at room temperature. Chemiluminescence was adopted to determine the concentration of adenosine triphosphate ( ATP ) and the activity of cysteinyl aspartate specific proteinase-3 ( caspase-3 ). The percentage of Annexin V positive platelets was determined by flow cytometry to reflect the level of phosphatidylserine ( PS ) exposure. Mean channel fluorescence ( MCF ) of platelets was determined by flow cytometry for reflecting the level of mitochondrial inner transmembrane potential (Δψm ) depolarization. RESULTS: Compared with control group, the ATP concentration in thrombin-treated group was decreased obviously [ relative light unit ( RLU ): ( 5.46±0.14 )×10(5) vs. ( 6.25±0.26 )×10(5), P < 0.05 ], Annexin V positive ratio [ ( 50.43±2.45 )% vs. ( 1.58±0.25 )%, P < 0.05 ] and caspase-3 activity [ RLU: ( 26.92±1.60 )×10(3) vs. ( 1.30±0.10 )×10(3), P < 0.05 ] were increased obviously, and platelets MCF was lowered significantly [ ( 8.32±0.58 )×10(4) vs. ( 13.05±1.10 )×10(4), P < 0.05 ], suggesting an increase in Δ ψm depolarization. After being treated with different concentrations of LPS, ATP concentration, Annexin V positive ratio and caspase-3 activity were increased obviously, platelet MCF was decreased obviously, suggesting Δψm depolarization was increased in a concentration-dependent manner. Compared with control group, 1 µg/mL LPS could increase Annexin V positive ratio [ ( 10.45±1.08 )% vs. ( 1.58±0.25 )%, P < 0.05 ], elevate caspase-3 activity [ RLU: ( 14.06±0.61 )×10(3) vs. ( 1.30±0.10 )×10(3), P < 0.05 ], and decrease MCF significantly [ ( 9.48±0.50 )×10(4) vs. ( 13.05±1.10 )×10(4), P < 0.05 ]. The ATP concentration, Annexin V positive ratio and caspase-3 activity reached maximum levels after the treatment with 100 µg/mL LPS, and they were higher obviously than those of the control group [ ATP ( RLU ): ( 7.00±0.03 )×10(5) vs. ( 6.25±0.26 )×10(5), Annexin V positive ratio: ( 55.35±2.42 )% vs. ( 1.58±0.25 )%, casepase-3 ( RLU ): ( 32.00±3.75 )×10(3) vs. ( 1.30±0.10 )×10(3), all P < 0.05 ], and platelets MCF reached trough levels, and they were obviously lower than those of the control group [ ( 4.69±0.55 )×10(4) vs. ( 13.05±1.10 )×10(4), P < 0.05 ]. CONCLUSIONS: E.coli LPS can induce an increase in ATP, PS exposure, Δψm depolarization and activity increase of caspase-3 on mouse platelet in vitro, which indicate that LPS can induce apoptosis of platelets in a concentration-dependent manner.


Assuntos
Apoptose/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Animais , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Escherichia coli/imunologia , Citometria de Fluxo , Técnicas In Vitro , Camundongos , Fosfatidilserinas
17.
Int Immunopharmacol ; 21(1): 128-36, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24819716

RESUMO

Signal transducer and activator of transcription protein 3 (STAT3), one of the major regulators of inflammation, plays multiple roles in cellular transcription, differentiation, proliferation, and survival in human diseases. Dysregulation of STAT3 is related to the severe airway inflammation associated with asthma. FLLL31 is a newly developed compound based on the herbal medicine curcumin, which specifically suppresses the activation of STAT3. However, the function of FLLL31 on inflammatory diseases, especially on the regulation of airway inflammation, has not been fully studied. In our prior investigations, we developed a mouse model that was challenged with a mixture of DRA allergens (including house dust mite, ragweed, and Aspergillums species) to mimic the severe airway inflammation observed in human patients. In this study, we performed a series of experiments on the inflammatory regulation activities of FLLL31 in both in vitro cultured cells and our in vivo DRA-challenged mouse model. Our results show that FLLL31 exhibits anti-inflammatory effects on macrophage activation, lymphocyte differentiation, and pro-inflammatory factor production. Importantly, FLLL31 significantly inhibited airway inflammation and recruitment of inflammatory cells in the DRA-challenged mouse model. Based on these results, we conclude that FLLL31 is a potential therapeutic agent that can be used against severe airway inflammation diseases.


Assuntos
Anti-Inflamatórios/administração & dosagem , Curcumina/análogos & derivados , Curcumina/administração & dosagem , Hipersensibilidade/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Ambrosia , Animais , Anti-Inflamatórios/farmacologia , Antígenos de Dermatophagoides/imunologia , Aspergillus , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Curcumina/farmacologia , Modelos Animais de Doenças , Feminino , Humanos , Hipersensibilidade/imunologia , Mediadores da Inflamação/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Pyroglyphidae , Fator de Transcrição STAT3/antagonistas & inibidores
19.
Yao Xue Xue Bao ; 48(8): 1183-8, 2013 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-24187823

RESUMO

P2X7 is the most important subtype of the ATP receptors known so far. Recent investigations showed that the downstream signaling pathway of P2X7 is coupled with several key inflammatory molecules including IL-1beta and IL-18, this suggests P2X7 might have roles in the inflammatory diseases. Moreover, attenuation of P2X7 by selective antagonists in vitro and knockout mice in vivo reducing the inflammatory response indicated that P2X7 is a potential therapeutic target for inflammatory diseases. However, most previous studies on P2X7 were focused on nerve system diseases most, while its effects in inflammatory respiratory diseases, especially in asthma, chronic obstructive pulmonary disease (COPD) and lung cancer have been poorly investigated. In this paper, we reviewed the research progress on the structure, distribution, biological activities of P2X7 and its relationship with inflammatory respiratory diseases including asthma, COPD and lung cancer, along with the development of P2X7 antagonist as therapeutics.


Assuntos
Inflamação/metabolismo , Antagonistas do Receptor Purinérgico P2X/uso terapêutico , Receptores Purinérgicos P2X7/metabolismo , Doenças Respiratórias/metabolismo , Animais , Asma/tratamento farmacológico , Asma/metabolismo , Humanos , Inflamação/tratamento farmacológico , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Camundongos , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Receptores Purinérgicos P2X7/química , Receptores Purinérgicos P2X7/genética , Doenças Respiratórias/tratamento farmacológico
20.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 32(5): 681-4, 2012 May.
Artigo em Chinês | MEDLINE | ID: mdl-22679734

RESUMO

OBJECTIVE: To observe the effects of Modified Liangge Powder (MLP) on the expressions of platelet toll like receptor 4 (TLR4) and the release of platelet-derived cytokines interleukin 8 (IL-8), beta platelet globulin (beta-TG), soluble CD40 ligand (sCD40L). METHODS: The modulating effects on the release of cytokines from mice platelets by TLR4 ligand through monoclonal antibody blocking TLR4 on platelet were compared. The stimulated platelet by LPS was incubated with low (0.94 g/mL), medium (1.89 g/mL), and high (2.84 g/mL) dose of MLP contained serum. The changes of the platelet TLR4 expression and platelet-derived cytokines were observed. RESULTS: The positive expression rate of platelet TLR4 obviously decreased (P < 0.01) and the release of sCD40L and beta-TG from platelets significantly increased (P < 0.01) after stimulated by LPS. However, the release of sCD40L and beta-TG from platelets obviously decreased by TLR4 monoclonal antibody (P < 0.05, P < 0.01). There was no statistical difference in IL-8 between before and after LPS stimulation (P > 0.05). Platelet TLR4 positive expression rate was significantly higher after incubated by medium and high doses of MLP contained serum (P < 0.01), and the releasing of sCD40L and beta-TG was lower in the serum contained groups. The inhibitory effects were enhanced in a dose-dependent manner. CONCLUSIONS: LPS induced platelet activation by TLR4 and released sCD40L and beta-TG, while the release of platelet IL-8 was not dependent on platelet TLR4-LPS pathway. MLP could inhibit LPS-stimulated sCD40L and beta-TG, inhibit the binding of platelet TLR4 and LPS in a dose-dependent manner, thus reducing the release of platelet cytokines.


Assuntos
Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Receptor 4 Toll-Like/metabolismo , Animais , beta-Globulinas/metabolismo , Ligante de CD40/metabolismo , Interleucina-8/metabolismo , Lipopolissacarídeos/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Soro
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