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Notch signaling pathway is a highly conserved signaling pathway in evolution, which would be activated to play a role in apoptosis, angiogenesis, neurogenesis, immune inflammation and others after ischemia. After acupuncture for ischemic stroke, the expression of Notch signaling pathways related factors increase, which may play a role in neurogenesis, ischemic tolerance, apoptosis, angiogenesis, and so on.
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Netrin-1 may protect and repair the damage caused by cerebral infarction, in terms of inhibiting apoptosis and inflammatory, and promoting angiogenesis and axon regeneration, etc. Netrin-1 may associate with the pathogenesis and outcome of cerebral infarction. The application of Netrin-1 in clinic needs more researches.
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This study aims to prepare nimodipine/tetramethylpyrazine-loaded poly(D, L-lactide-co-glycolide) dual-drug nanoparticles (NMD/TMP-NPs) and investigate pharmacokinetics and brain distribution to evaluate the possibility of enhancing the drug effect of dual-drug nanoparticles. NMD/TMP-NPs were prepared via W/O/W emulsion solvent evaporation. Entrapment efficiency and drug loading of NMD/TMP-NPs were investigated by ultracentrifugation, and drug release behavior in vitro was studied by dialysis method. The pharmacokinetic and brain distribution were studied in SD mice administered intravenously with NMD/TMP-NPs in comparison with NMD-suspension, NMD/TMP-suspension and NMD-NPs, (NMD-NPs+TMP)-suspension. According to the results, the entrapment efficiency and drug loading of NMD were (79.71±0.73)%, (1.74±0.02)%, those of TMP were (40.26±1.51)% and (4.38±0.16)%. The nanoparticles showed the property of sustained release. On the basis of the major parameters for in vivo pharmacokinetic and brain distribution, t1/2β of NMD-suspension, NMD/TMP-suspension and NMD-NPs, (NMD-NPs+TMP)-suspension, NMD/TMP-NPs were (1.097±0.146), (1.055±0.06), (1.950±0.140), (1.860±0.096), (2.497±0.475） h, CL were (0.778±0.098), (1.133±0.111), (0.247±0.023), (0.497±0.040), (0.297±0.024) h•L-1, AUC0-t in rat plasma were (514.218±60.383), (352.916±33.691), (1 618.429±240.198), (804.110±75.804), (1 349.058±215.497) μg•h•L⁻¹, respectively, and AUC0-t in brain were 0.301 9, 0.624 8, 1.068 6, 1.313 0, 1.046 5 mg•h•L⁻¹, respectively. According to the in vivo study, the pharmacokinetic behavior of NMD were markedly prolonged by adding TMP or prepared dual-drug nanoparticles.
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Curcumin has a wide spectrum of pharmaceutical properties such as antitumor, antioxidant, antiamyloid, and anti-inflammatory activity. However, poor aqueous solubility and low bioavailability of curcumin are major challenge in its development as a useful drug. To overcome many of these problems, curcumin-loaded long-circulating liposomes (Cur-LCL) were prepared by the ethanol injection method. Morphology of Cur-LCL was observed by transmission electron microscope, mean particle size and Zeta potential were detected by laser particle size analyzer, entrapment efficiency and drug loading were evaluated by ultracentrifugation. The drug release behavior in vitro and pharmacokinetic behavior in rats of Cur-LCL were investigated with curcumin (Cur) and curcumin liposomes (Cur-Lips) as control. The results showed that the mean diameter of Cur-LCL was 110 nm, the Zeta potential was -5.8 mV. The entrapment efficiency and drug loading of Cur-LCL was 80.25%, 2.06%, respectively. The release behavior in vitro studied by dialysis in PBS buffer showed significant sustained release profile that 48.95% Cur were released from Cur-LCL in 7 h, 88.92% in 24 h. The pharmacokinetic parameters showed that compared with Cur and Cur-Lips, the t(1/2beta) of Cur-LCL was extended to 13 and 1.8-fold, respectively. Besides, the AUC values was significantly increased (P < 0.01), and the clearance was evidently decreased (P < 0.01). These results from in vitro and in vivo indicated that Cur-LCL were able to realize controlled drug release and increase circulation time.
Subject(s)
Animals , Female , Humans , Male , Rats , Curcumin , Chemistry , Pharmacokinetics , Delayed-Action Preparations , Chemistry , Pharmacokinetics , Drug Carriers , Chemistry , Liposomes , Chemistry , Particle Size , Rats, Sprague-Dawley , SolubilityABSTRACT
OBJECTIVE: To prepare nimodipine/tetramethylpyrazine-loaded poly[poly (lactic-co-glycolic acid), PLGA] dual-drug nanoparticles (nimodipine/tetramethylpyrazine-PLGA-nanoparticles, NMD/TMP-PLGA-NPs), and investigate the in vitro release behavior and brain distribution. METHODS: NMD/TMP-PLGA-NPs were prepared by optimized emulsion solvent evaporation method with PLGA as a carrier material; the morphology of NMD/TMP-PLGA-NPs was observed by transmission electron microscope; the mean particle size, particle size distribution and Zeta potential were measured by laser particle size analyzer; the entrapment efficiency and drug loading were measured by ultracentrifugation; the in vitro release behavior was studied by dialysis; the brain distribution was compared with NMD-suspension and NMD-PLGA-NPs. RESULTS: The NMD/TMP-PLGA-NPs were spherical; the mean particle size, particle size distribution and Zeta potential of NPs were (631.60±3.20) nm, (0.097±0.007), (-29.25±1.87) mV, respective-ly. The entrapment efficiency and drug loading of NMD were (76.25±1.18)% and (1.24±0.01)%, while those of TMP were (39.30±1.00)% and (6.34±0.11)%, respectively. The profiles of in vitro release had the features of sustained release. The ALC0→t of NMD-suspension, NMD-PLGA-NPs and NMD/TMP-PLGA-NPs were 0.2683, 0.4596 and 0.8815 μg·min·mL-1, and the addition of TMP promoted the reach of highest brain concentration. CONCLUSION: NMD/TMP-PLGA-NPs are prepared successfully and show sustained-release in vitro, and the distribution of NMD into brain was increased significantly with the addition of TMP.
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Rett syndrome (RTT) is a disorder characterized by regression of spoken language and hand use,distinctive hand stereotypies,accompanying with severe psychomotor developmental retardation and retrogression.RTT becomes recognizable at 6-18 months and female are absolutely susceptive.MECP2 mutations are closely related to the development of RTT.Revised diagnostic criteria for RTT (2010) ensure a high degree of homogeneity in cases enrolled in treatment and clinical studies throughout the world.As for the treatment,no crucial advancement has been clinically applied recently,but some valuable basic research is in progress.This paper reviews the genetic research,clinical diagnosis and treatment of RTT,and promotes understanding of the new diagnostic criteria and basic research.
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<p><b>OBJECTIVE</b>To introduce a new sequential chlorination disinfection process in which short-term free chlorine and chloramine are sequentially added.</p><p><b>METHODS</b>Pilot tests of this sequential chlorination were carried out in a drinking water plant.</p><p><b>RESULTS</b>The sequential chlorination disinfection process had the same or better efficiency on microbe (including virus) inactivation compared with the free chlorine disinfection process. There seemed to be some synergetic disinfection effect between free chlorine and monochloramine because they attacked different targets. The sequential chlorination disinfection process resulted in 35.7%-77.0% TTHM formation and 36.6%-54.8% THAA5 formation less than the free chlorination process. The poorer the water quality was, the more advantage the sequential chlorination disinfection had over the free chlorination.</p><p><b>CONCLUSION</b>This process takes advantages of free chlorine's quick inactivation of microorganisms and chloramine's low disinfection by-product (DBP) yield and long-term residual effect, allowing simultaneous control of microbes and DBPs in an effective and economic way.</p>