RESUMO
Objective To prepare SDF-1 α-loaded nanoliposome ( SNP )-SonoVue complex and investigate its tracing abilities, sustained-release property and effect on migration of bone marrow mesenchymal stem cells (BMSCs). Methods The SNP was prepared to detect its physical characteristics including particle size,zeta potential, morphology, encapsulation efficiency and drug loading.SNP-SonoVue was constructed to detect the sustained release situation of SNP and SNP-SonoVue after low frequency ultrasound ( LIFU ) irradiation, and the connection of SNP-SonoVue was observed by fluorescence microscope. Effects of SNP-SonoVue on migration of BMSCs were detected to evaluate its bioactivity. BMSCs were divided into 6 groups,including Group A: SDF-1α+ 1% serum medium;Group B: SNP- SonoVue+ 1% serum culture medium;Group C:SNP-SonoVue+ 1% serum culture medium + LIFU ( 1 MHz,0.5 W/cm2, expose 30 s stop 30 s, 4 min);Group D: BNP-SonoVue+1% serum medium;Group E:BNP-SonoVue+1% serum medium+LIFU ( 1 MHz, 0.5 W/cm2, expose 30 s stop 30 s, 4 min),Group F:PBS+1% serum culture medium (control group). Its tracing abilitie were investigated in vitro. Results The average particle size of SNP was(220.4±9.9)nm,and the particle dispersion index(PDI) was(0.172± 0.015), the average zeta potential was ( 35.6 ± 1.7) mv. It was showed spherical dispersion by transmission electron microscopy. The encapsulation efficiency was up to 96.7% and the drug entrapment content was 481.76 ng/mg. Flow cytometric showed the suitable conditions for SNP-SonoVue preparation was that the ratio of SNP quality(mg) to Sono Vue microbubbles number(a) was20:(2.8×109)to40:(2.8× 109). Fluorescence microscopy showed that shells of SonoVue microbubbles connected with large numbers of SNP labeled with red fluorescent DiI. Drug release experiment showed that the cumulative SDF-1α release amount of SNP and SNP-SonoVue exposed to LIFU respectively were ( 68.61 ± 3.97 )% and ( 63.21 ± 5.68)% in vitro within 7 days, and the difference was not statistically significant ( P ＞ 0.05 ). Cell migration experiments confirmed that the transfer function of BMSCs in Group A, Ggroup B and group C was significantly higher than that in control group ( P ＜ 0.05 ), but there was no significant difference among the Group A, Ggroup B and group C ( P ＞0.05). In vitro development experiment showed that the SNP-SonoVue complex had obviously enhanced development effect. Conclusions SNP-SonoVue complex is successfully prepared. It has obviously enhanced development effect and can lead to migration of BMSCs.
RESUMO
Objective To investigate the characteristics of amygdala neural circuitry in comorbidity of late-life depression (LLD) and cognitive impairment. Methods Twenty-four LLD,eighteen amnestic mild cognitive impairments (aMCI),thirteen aMCI with depression (dMCI) and thirty cognitive normal (CN) subjects completed resting-state functional magnetic resonance imaging scan. Main effects of depression and MCI and their interactions on the intrinsic amygdala functional connectivity network ( AFCN) connectivity were examined. Behavioral significance of AFCN that voxel-wised amygdala connectivity correlating with de-pression severity and memory scores were also tested after controlling the effects of covariates,including age, gender,education, gray matter atrophy, and group. Results The immediate memory and delayed memory function in the aMCI group (-0. 75 ± 0. 77 and -1. 13 ± 0. 56) and the dMCI group (-1. 07 ± 0. 79 and-1. 00±0. 52) were significantly lower than those of the CN group (0. 46±0. 73 and 0. 60±0. 61),and the difference was statistically significant (P<0. 01). Depression and anxiety in the LLD group (1. 00±0. 53 and 0. 93±0. 98) and the dMCI group (0. 86±0. 80 and 0. 78±0. 82) were significantly higher than those of the CN group (-0. 92±0. 25 and -0. 74±0. 22),and the difference was statistically significant (P<0. 01). Brain network analysis showed that separated neural circuits were implicated in the depression and cognitive im-pairment. Importantly,interactive effects of depression and MCI on the AFCN were also identified,especially in the bilateral somatomotor area,inferior parietal cortex/precuneus,posterior cingulate cortex,right medial prefrontal cortex/dorsolateral prefrontal cortex and hippocampus. Behavioral significance of AFCN also re-vealed the distinctive neural circuits involved in the depression severity and memory deficits,respectively. Conjunction analysis further identified the overlapped neural circuits associated with depression and memory deficits were primarily in the left DLPFC,insula,hippocampus,right inferior prefrontal cortex and dorsomedi-al prefrontal cortex. Conclusions Depression and cognitive impairment synergistically facilitate functional decoupling of AFCN and thus compromise the integrity of amygdala networks. Distinct depression-related or MCI-related neural constructs represent the characteristics of clinical phenotype of depression or MCI alone, while overlapped circuits probably reveal the neural basis of comorbidity of LLD and MCI.