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OBJECTIVE Tissue plasminogen activator (tPA) is the only approved pharmaco-logical therapy for acute brain ischaemia;however,a major limitation of tPA is the haemorrhagic trans-formation that follows tPA treatment. Here, we determined whether nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide biosynthesis, affects tPA-induced haemorrhagic transformation. METHODS Middle cerebral artery occlusion (MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 h.When the filament was removed for reperfusion, tPA was infused via the tail vein.A single dose of NMN was injected i.p.(300 mg·kg-1).Mice were killed at 24 h post ischaemia, and their brains were evaluated for brain infarction, oedema, haemoglobin content, apoptosis, neuroinflammation, blood-brain barrier (BBB) permeability, the expression of tight junction proteins(TJPs)and the activity/expression of MMPs. RESULTS In the mice infused with tPA at 5 h post ischaemia, there were significant increases in mortality, brain infarction, brain oedema, brain haemoglobin level, neural apoptosis, Iba-1 staining (microglia activation) and myeloperoxidase staining (neutrophil infiltration). All these tPA-induced alterations were significantly prevented by NMN administration. Mechanistically, the delayed tPA treatment increased BBB permeability by down-regulating TJPs, including claudin-1, occludin and zonula occludens-1,and enhancing the activities and protein expression of MMP9 and MMP2. Similarly, NMN administration partly blocked these tPA-induced molecular changes. CONCLUSION Our results demonstrate that NMN ameliorates tPA-induced haemorrhagic transformation in brain ischaemia by maintaining the integrity of the BBB.
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Objective To develop a new type of anti-fatigue nutrient chewable tablet and to explore its anti-fatigue effect in mice. Methods Ginseng polysaccharide, acanthopanax extract and taurine were mixed together in a proportion of 6 : 8 : 1 as remedium cardinale, mannitol was used as filler, sucrose as a correctant and magnesium stearate as a lubricant. Hardness, appearance and taste were utilized as score indexes, the dosage of mannitol, sucrose, and magnesium stearate were used as study factors. The orthogonal test was applied to screen the best proportion of raw materials to create the formulation according to the mouse behaviors. A total of 60 male mice were randomly divided into control group (normal saline) and three doses of Shenjia chewable tablet groups (200, 600 and 1 800 mg kg). Lavage administration was lasted for 7 days. We then carried out the weight loading swimming test to record the swimming lime of mice, and also recorded the body mass and the serum biochemical indexes, including adenosine triphosphate (ATP), lactic acid (Lac), free triiodothyronine (FT3). free thyroid hormone (FT4). cortisol and melatonin (MT). Results The formulation was optimized as 30% ginseng polysaccharide, 40% acanthopanax extract, 5% taurine. 19% mannitol, 5% sucrose, and 1. 0% magnesium stearate. The Shenjia chewable tablet tasted cool and sweet, round in shape, yellow in color and smooth in appearance. Compared with the control group, there were significant increases in the loaded-swimming time in the three doses groups (P<0. 01), in the levels of ATP, FT3, FT4 and MT in middle and high dosage groups (P<0. 05, P<0. 01), and in Lac level in high dosage group (P
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Objective: To study the mechanism of chitosan i n inhibiting the proliferation of rabbit aortic smooth muscle cells(SMCs). Methods: By means of c-myc probe labelled with random primers and Northern blot hybridization, we examined the effect of chitosan on vascu lar SMC c- myc mRNA expression, which was stimulated by newborn bull serum (NB S,20%). Results: The oncogene c-myc mRNA expression incerased in cultured vascular SMC 24 h after NBS exposure. These effects were inhibite d by chitosan (20 μg/ml). Conclusion: Chitosan might inhibit the expression of vascular SMC c-myc mRNA stimulated by NBS, through which the proliferation of vascular SMC are inhibited.
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Objective: To study the mechanism of chitosan i n inhibiting the proliferation of rabbit aortic smooth muscle cells(SMCs). Methods: By means of c-myc probe labelled with random primers and Northern blot hybridization, we examined the effect of chitosan on vascu lar SMC c- myc mRNA expression, which was stimulated by newborn bull serum (NB S,20%). Results: The oncogene c-myc mRNA expression incerased in cultured vascular SMC 24 h after NBS exposure. These effects were inhibite d by chitosan (20 μg/ml). Conclusion: Chitosan might inhibit the expression of vascular SMC c-myc mRNA stimulated by NBS, through which the proliferation of vascular SMC are inhibited.