RESUMEN
Cell death is one of the basic life properties. A new type of cell death named necroptosis was discovered and became increasingly noticed attention in recent years. Necroptosis has similar morphological characteristics with cell necrosis and is controlled by special signal pathways. The interaction of the receptor interacting protein 1 (RIP1) and 3 (RIP3) plays a crucial important role in the necroptosis signal pathway. The RIP1 determines whether a cell goes survival and death, and the RIP3 determines the pathway of cell death apoptosis or necrosis. This paper summarizes the knowledge about the necroptosis signal pathways and explores its significance in the organ ischemic injury, inflammation and tumor pathogenesis briefly.
Asunto(s)
Apoptosis , Necrosis , Proteína Serina-Treonina Quinasas de Interacción con Receptores/fisiología , Humanos , Inflamación , Transducción de SeñalRESUMEN
Organic anion transporters (OATs) belong to a family of poly-specific transporters mainly located in barrier epithelia such as renal proximal tubule, brain, liver and placenta. OATs interact with endogenous metabolic end products such as urate and acidic neutrotransmitter metabolites, as well as with a multitude of widely used drugs, including antibiotics, diuretics, antihypertensives and anti-inflammatory drugs. Thereby, OATs play an important role in renal drug elimination and have an impact on pharmacokinetics. This review summarizes current knowledge of the properties and functional roles of the cloned OAT family members detailed in tissue differences in expression and physiologic function, drug-drug interactions, and finally, gender-dependent regulation in health and diseased states.
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Transportadores de Anión Orgánico/fisiología , Animales , Antibacterianos/farmacocinética , Antihipertensivos/farmacocinética , Diuréticos/farmacocinética , Humanos , Túbulos Renales Proximales/metabolismo , Hígado/metabolismo , Transportadores de Anión Orgánico/genética , Transportadores de Anión Orgánico/metabolismo , Ácido Úrico/metabolismoRESUMEN
BACKGROUND: Abelmoschus manihot (L.) Medic flower is a medicinal plant for the treatment of diseases in China. The present study was carried out to scientifically validate the gastroprotective activity and clarify the possible mechanism of the total flavones from Abelmoschus manihot (L.) Medic flower is a medicinal plant for the treatment of diseases in China. The present study was carried out to scientifically validate the gastroprotective activity and clarify the possible mechanism of the total flavones from. METHODS: Gastric ulcer was induced in mice by oral administration of ethanol. The gastroprotective activity of TFA was evaluated by the gastric ulcer index and histological examinations. The gastric tissue was collected in the form of homogenate. The level of malondialdehyde (MDA) and glutathione (GSH), the activity of superoxide dismutase (SOD), and protein content were measured. Western blotting for the expression of Bax, Bcl-2, TNF-α, and NF-κB(p65) was also carried out. The effect of TFA was compared with that of standard antiulcer drug omeprazole (100 mg/kg). RESULTS: This gastroprotective effect of TFA could be attributed to the increase in the activity of SOD and GSH and decrease in the levels of MDA and also decrease in the levels of Bax, TNF-α, and NF-κB(p65) was also carried out. The effect of TFA was compared with that of standard antiulcer drug omeprazole (100 mg/kg). CONCLUSION: The findings of this study demonstrated that TFA could significantly attenuate ethanol-induced gastric injury via antioxidative, anti-inflammatory, and antiapoptotic effects.
RESUMEN
In the title compound, C(11)H(17)ClNO(+)·Cl(-), the side chain of the ethyl-amine group is orientated approximately perpendicular to the benzene ring, the dihedral angle between the C/C/N plane of the ethyl-amine group and the benzene plane being 83.5â (3)°. In the crystal structure, inter-molecular O-Hâ¯Cl and N-Hâ¯Cl hydrogen bonds are observed. The crystal studied was an inversion twin with a 0.51â (10):0.49â (10) domain ratio.
RESUMEN
AIM: To survey the uptake behavior and subcellular distribution of antisense oligodeoxynucleotide polymethacrylate submicroparticles (AS-ODN-SMP) and infer its mechanism in MGC cell lines. METHODS: MGC cells were incubated at certain concentration of AS-ODN-SMP or AS-ODN for 8 h at 4 degrees C or 37 degrees C. Then the fluorescence oligodeoxynucleotide- labeled cells were counted by flow cytometer and the intracellular fluorescence intensity was determined after incubated with chloroquine for 2 h. RESULTS: Cellular uptake of oligodeoxynucleotides was significantly increased following application of AS-ODN-SMP and total intracellular fluorescence intensity was enhanced by 683 folds with the vehicle concentration of 20 microg x mL(-1). AS-ODN-SMP entranced to cells profoundly with temperature-dependent manner. Rare cells took on fluorescence when incubated at 4 degrees C, while 37 degrees C they were significantly increased. But the intracellular fluorescence intensity appeared same level in present or absent of chloroquine. CONCLUSION: With the help of polyacrylate submicroparticles, oligonucleotides efficiently entranced the cells via endocytosis and could successfully escape the degradation in lysosome.
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Sistemas de Liberación de Medicamentos , Endocitosis/efectos de los fármacos , Células Gigantes/citología , Oligodesoxirribonucleótidos Antisentido , Ácidos Polimetacrílicos/farmacología , Animales , Línea Celular , Portadores de Fármacos , Lisosomas/metabolismo , Nanopartículas , Oligodesoxirribonucleótidos Antisentido/administración & dosificación , Oligodesoxirribonucleótidos Antisentido/farmacocinética , Tamaño de la Partícula , Ácidos Polimetacrílicos/química , TemperaturaRESUMEN
Human basic fibroblast growth factor (bFGF) is a potent neuroprotective agent. The clinical efficacy of this neurotrophin, however, is restricted by poor permeability across the blood-brain barrier (BBB). This study was designed to test the hypotheses that bFGF will retain its biological activity and have an enhanced BBB transport after re-formulation and conjugation to a BBB peptide drug delivery vector. The BBB delivery vector is comprised of a conjugate of streptavidin (SA) and the murine OX26 monoclonal antibody against the rat transferrin receptor, and the conjugate of biotinylated bFGF (bio-bFGF) bound to a vector is designated bio-bFGF/OX26-SA. A radioreceptor binding assay shows that the native bFGF, bio-bFGF, and bio-bFGF/OX26-SA conjugate have IC50 values of 0.12, 0.40, and 0.56 nM, respectively. After an IV bolus injection to the rat, [125I]-bio-bFGF is avidly taken up by peripheral organs, with low brain uptake at 60 min, 0.010+/-0.004% of injected dose (ID)/g brain. By contrast, the brain uptake of the [125I]-bio-bFGF/OX26-SA is increased 5-fold to 0.050+/-0.011%ID/g, although the uptake of the conjugate by peripheral tissues was decreased relative to the unconjugated bio-bFGF. In conclusion, conjugation of bio-bFGF to a BBB drug delivery vector (a) causes only a minor decrease in affinity for the bFGF receptor, (b) decreases the peripheral organ uptake of the bFGF, and (c) increases the brain uptake of the neurotrophin. The re-formulation of bFGF to enable receptor-mediated transcytosis across the BBB may improve the therapeutic index of this neurotrophin as a neuroprotective agent.
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Barrera Hematoencefálica/fisiología , Encéfalo/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Factor 2 de Crecimiento de Fibroblastos/farmacocinética , Algoritmos , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/farmacocinética , Área Bajo la Curva , Sitios de Unión , Biotinilación/métodos , Barrera Hematoencefálica/efectos de los fármacos , Encéfalo/efectos de los fármacos , Arterias Carótidas , Factor 2 de Crecimiento de Fibroblastos/administración & dosificación , Factor 2 de Crecimiento de Fibroblastos/química , Humanos , Infusiones Intraarteriales , Radioisótopos de Yodo , Riñón/metabolismo , Hígado/metabolismo , Pulmón/metabolismo , Masculino , Ratones , Miocardio/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Ensayo de Unión Radioligante , Ratas , Ratas Sprague-Dawley , Receptores de Transferrina/inmunología , Estreptavidina/administración & dosificación , Estreptavidina/química , Estreptavidina/farmacocinética , Distribución TisularRESUMEN
OBJECTIVE: To investigate the effect of nerve growth factor (NGF) on lipopolysaccharide (LPS) injury and activation of nuclear factor-kappa B in PC12 cells. METHODS: In order to set injury models, the PC12 cells were incubated in different concentration of LPS. Cells were cultured in the culture and were reduced by LPS, and then cells were treated by NGF of various concentrations. The cell viability was determined by methyl thiazolyl tetrazolium (MTT) assay, cellular morphology was observed under inverted microscope and fluorescence microscope, and the content of NF-kappaB was assessed by RT-PCR. RESULTS: (1) The viability of PC12 cell was decreased with concentration of LPS increasing. (2) The cellular morphology change showed that NGF had an ability to reduce LPS injury. (3) The result of RT-PCR showed that the content of NF-kappaB in LPS injury was more than the normal and treated cell, and the treated one was close to the normal one. CONCLUSION: The reports about NGF in brain cells repair after inflammatory are very small. And our study is about that NGF can protect the PC12 cell from LPS injury, and this mechanism possible bears on the activation of NF-kappaB.
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Lipopolisacáridos/toxicidad , Factor de Crecimiento Nervioso/farmacología , Fármacos Neuroprotectores/farmacología , Animales , FN-kappa B/metabolismo , Células PC12 , RatasRESUMEN
AIM: To explore the effects of sinomenine(Sin) on intracellular free calcium ([Ca2+]i) and the activity of PKC (protein kinase C) of the cultured aortic vascular smooth muscle cells (VSMC) during ischemia and hypoxia. METHODS: The effect of Sin on changes in [Ca2+]i were determined in cultured rabbit VSMC after exposure to high K+, norepinephrine (NE) and caffeine (Caf). Fluorescent Ca2+ -indicater fura-2/AM was used. The effects of Sin were compared with that of verapamil (Ver). The hypoxia model was made, then the activity of PKC was measured by y scintillation counting instrument. RESULTS: Sin (10 x 10(-6) mol x L(-1), 3 x 10(-5) mol x L(-1) 10(-4) mol x L(-1)) inhibited the elevation of [Ca2+]i induced by high K+ -depolarization in a concentration dependent manner. In addition, Sin inhibited the elevation of [Ca2+]i induced by NE in the presence of extracellular Ca2+. In the absence of extracellular Ca2+, Sin (3 x 10(-5) mol.L(-1)) also had no blocking effect on the NE-induced [Ca2+]i increase. It was found that the activity of PKC treated with Sin in VSMC cytoplasm and cell membrane in normal condition increased, the activity of PKC in cytoplasm in ischemia and hypoxia situation increased, but the activity of PKC in cell membrane decreased. When VSMC was treated with Sin, the activity of PKC in cytoplasm decreased and that of cell membrane increased. CONCLUSION: The results suggest that Sin might decrease the[Ca2+] i of VSMC by blocking both VDC and ROC, could regulate the PKC activities induced by ischemia and hypoxia.
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Calcio/metabolismo , Morfinanos/farmacología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Proteína Quinasa C/metabolismo , Animales , Aorta/citología , Aorta/efectos de los fármacos , Hipoxia de la Célula , Células Cultivadas , Citoplasma/metabolismo , Músculo Liso Vascular/citología , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/fisiología , ConejosRESUMEN
Basic fibroblast growth factor (bFGF) has minimal pharmacological effects in the central nervous system in the absence of blood-brain barrier (BBB) disruption. BBB transport of bFGF occurs via an absorptive-mediated transcytosis mechanism, which is relatively inefficient. To enhance the BBB transport of bFGF, this neurotrophin was reformulated to enable receptor-mediated transport across the BBB via the transferrin receptor. bFGF was monobiotinylated and coupled to a BBB drug-delivery vector comprised of streptavidin (SA) and the OX26 monoclonal antibody to the rat transferrin receptor. The entire conjugate of biotinylated bFGF bound to the OX26-SA is designated bio-bFGF/OX26-SA. The bFGF retains receptor-binding affinity and has increased brain uptake following conjugation to OX26-SA. The bio-bFGF/OX26-SA conjugate protects cortical cell cultures against hypoxia/reoxygenation insult in a dose-dependent manner in vitro. A single intravenous injection of bio-bFGF/OX26-SA, equivalent to a dose of 25 microg/kg bFGF, produces an 80% reduction in infarct volume in the brain of rats subjected to permanent occlusion of the middle cerebral artery in parallel with a significant improvement of neurologic deficit. The neuroprotection is time-dependent, and there is a 67% reduction in stroke volume if the conjugate is administered at 60 min after arterial occlusion, whereas no significant reduction in stroke volume is observed if treatment is delayed 2 h. In conclusion, neuroprotection in regional brain ischemia is possible following the delayed intravenous injection of low doses of bFGF providing the neurotrophin is conjugated to a BBB drug-targeting system.