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OBJECTIVE To study the tissue distribution characteristics of curcumin solid lipid nanoparticles （Cur-SLN） in rats. METHODS Cur-SLN was prepared with microemulsion. SD rats were randomly divided into Cur raw material group and Cur- SLN group， with 45 rats in each group. The rats of two groups were injected with the corresponding drugs （by Cur， 25 mg/kg） by single intravenous injection. The heart， lung， kidney and liver tisse were separated at 0.25， 0.5， 1， 2， 4， 6， 8， 12 and 24 h after administration. The contents of Cur in different tissues were determined by high-performance liquid chromatography method. Their tissue distribution was analyzed. RESULTS The linear range of detected mass concentration of Cur in heart， lung， kidney and liver tissues were 0.064 75-129.50， 0.064 75-64.75， 0.064 75-129.50， 0.064 75-129.50 μg/mL， respectively （all r＞0.99）. The lower limits of quantitation were all 0.064 75 μg/mL， and the limit of detection were all 0.012 95 μg/mL. The intra-day and inter-day precision， accuracy and extraction recovery were in line with the requirements of quantitative analysis. Compared with Cur raw material group， the contents of Cur in heart， kidney， lung （at each time point of 0.25-24 h） and liver tissue （at each time point of 0.25-1 h， 12-24 h） of samples were significantly increased in the Cur-SLN group （P＜0.05 or P＜0.01）， while the contents of Cur in liver tissue （at each time point of 2-8 h） were significantly decreased （P＜0.01）. CONCLUSIONS After Cur was prepared into solid lipid nanoparticles， its distribution in heart， kidney and lung tissues is increased.
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@#Gene editing tools with nucleases as the main component have now implemented programmable targeted mutagenesis or insertion or deletion of mammalian genomes.From zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), CRISPR/Cas system to safer and more accurate Cas9 fusion protein gene editing tools and other nuclease gene editing tools, this paper systematically describes the development and evolution of gene editing, with detailed introduction to the development and optimization of next-generation gene editing tools, and a prospect of the clinical application of and challenges for gene editing tools.
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Objective:To analyze clinical and imaging features of Sturge-Weber syndrome in children.Methods:Clinical data were collected from 27 children with Sturge-Weber syndrome in Xuzhou Children′s Hospital, Xuzhou Medical University from July 2013 to December 2019, and analyzed retrospectively.Results:Among the 27 children, 17 were males and 10 were females. Their age at the clinic visit ranged from 2 days to 10 years and 7 months, and averaged 2.54 years. All the 27 patients presented with facial port-wine stains of varied color from light red to purple red, which were all distributed across the facial midline, including 21 with predominantly unilateral port-wine stains and 6 with bilateral symmetrical port-wine stains. There were 17 patients with ocular choroidal vascular malformations, including 14 with congenital glaucoma, 5 with high intraocular pressure, and 1 with optic nerve atrophy accompanied by transient blindness. Neurological impairment occurred in 12 patients, and all manifested as epilepsy. All the 27 children underwent imaging examination, and abnormalities were found in 20. Among the 10 patients with abnormal computed tomography images, local calcification was observed in 8, and local thickening of the skull on the side affected by skin lesions in 8; 13 of 14 patients with abnormal magnetic resonance imaging scan results had signs of brain atrophy, 9 showed enhanced gyrus-like blood vessel formation by enhanced magnetic resonance imaging, and 5 showed decreased branches of the anterior and middle cerebral artery on the affected facial side by magnetic resonance angiography.Conclusions:Children with Sturge-Weber syndrome are clinically characterized by predominantly unilateral port wine stains on the face, some of whom are accompanied by epilepsy, glaucoma or mental retardation, and imaging examinations mainly show local calcification, brain atrophy, local thickening of the skull plate, enhanced gyrus-like blood vessel formation, etc. Early definite diagnosis and comprehensive systemic treatment are needed to reduce disability and mortality rates in patients with Sturge-Weber syndrome, and long-term follow-up should be considered.
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OBJECTIVE：To study the effects of Cu rcumin solid lipid n anoparticels （Cur-SLN） on cardiac ，renal and pulmonary functions ，the expression of autophagy related factors in cardiorenal syndrome model rats. METHODS ：The rats were divided into sham operation group ，model group ，rapamycin group （positive control ，2 mg/kg），Cur-SLN low-dose and high-dose groups（5，10 mg/kg），except for 13 rats in the model group （3 of which are used to judge whether modeling is successful ），10 rats in the other groups. Except for sham operation group ，cardiorenal syndrome of other groups were induced by abdominal aortic coarctation combined with acute renal ischemia-reperfusion injury. After successful modeling ，rats in each administration group were injected with corresponding drugs through caudal vein ，and rats in sham operation group and model group were injected with equal volume normal saline ，once a day for 4 weeks. Twenty-four hours after the last administration ，the contents of angiotensin converting enzyme （ACE），free triiodothyronine （FT3） and arginine vasopressin （AVP） in rat serum were detected. The pathological morphology of rat heart ，kidney and lung were observed. The distribution and expression of LC 3 and Beclin- 1 protein in rat heart ，kidney and lung were detected. RESULTS ：Compared with sham operation group ，the contents of ACE and FT 3 in serum，the indexes of heart and kidney ，the expression of LC 3（except in renal tissue ）and Beclin- 1 protein in heart ，kidney and lung were significantly increased （P＜0.01），and the contents of AVP and lung index were decreased significantly （P＜0.01）； myocardial cells in the non-infarcted area of the heart were obviously hypertrophic ，the arrangement of myocardial fibers was disordered ； the structure of renal tubules in the non-infarcted area of the kidney was disordered ；and there was cystic expansion and obvious inflammatory cell infiltration llittls- in the alveoli ；positive expression of LC 3 and Beclin- 1 protein nows@126.com in heart ，kidney and lung increased ，mainly distributed in the cytoplasm of cardiomyocytes ，distal renal tubular epithelial cells ，alveolar macrophages and epithelial cells. Compared with model group，the above indexes of rats in each dose group of Cur-SLN were mostly significantly reversed ；the pathological changes of heart，kidney and lung tissues were reduced ，the infiltration of inflammatory cells was reduced ；and the positive expression of LC 3 and Beclin- 1 protein were reduced ，which were mainly distributed in the cytoplasm of cardiomyocytes and proximal renal tubular epithelial cells ，and a few in distal renal tubular epithelial cells ，alveolar macrophages and epithelial cells. CONCLUSIONS ： Cur-SLN can improve the heart ，kidney and lung functions of rats with cardiorenal syndrome ，and its mechanism may be related to regulating the distribution or expression of LC 3 and Beclin- 1 protein in heart ，kidney and lung.
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OBJECTIVE:To study the effects of Shenfu qiangxin(SFQX)pills on the expression of autophagy-associated pro-tein LC3b and pro apoptotic gene Bax in myocardial cells of rats with cardiorenal syndrome (CRS). METHODS:Rats were ran-domly divided into sham operation group(water),model group(water),positive control group(Captopril tablets 2.3 mg/kg)and SFQX pills high-dose,medium-dose and low-dose groups [13.2,6.6,3.3 g(crude drug)/kg],with 10 rats in each group. CRS mod-el was induced in those groups by abdominal-aortae-constriction+acute renal ischemia reperfusion injury except for sham operation group;and they were given relevant medicine intragastrically 8 week after operation,once a day,for consecutive 4 weeks. Plasma contents of Cr and ALD,the protein expression of LC3b and Bax in myocardial tissue of rats were detected 24 h after last medica-tion;ventricular index was calculated,and morphological change of myocardial tissue was observed. RESULTS:Compared with sham operation group,the plasma contents of Cr and ALD,ventricular index and the protein expression of LC3b in myocardial tis-sue increased significantly in model group (P<0.05 or P<0.01);and myocardial cell suffered from endochylema red deletion, myocardial cross striation disorder,intercellular space fibrosis aggravation and so on. Compared with model group,the plasma con-tents of Cr and ALD(except for positive control group)and the protein expression of LC3b and Bax in myocardial tissue decreased significantly in positive control group and SFQX pills high-dose group(P<0.05 or P<0.01);myocardial pathological change was improved;the ventricular index decreased significantly in SFQX pills low-dose and medium-dose groups (P<0.05). CONCLU-SIONS:SFQX pills can decrease the plasma contents of Cr and ALD,inhibit myocardial cell autophagy and apoptosis in CRS rats.
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OBJECTIVE:To establish a method of determining the plasma concentration of capecitabine/polyethylene glycol 1000/montmorillonite (CAP/PEG1000/MMT) in rats’plasma for the study on pharmacokinetics of CAP compound in rats in vivo. METHODS:HPLC was adopted. The determination was performed on Kromasil C18 with mobile phase consisted of 0.1% glacial acetic acid-acetonitrile(73∶27),at the flow rate of 1.0 ml/min. The detection wavelength was 250 nm and column temperature was 40 ℃. The sample size was 10 μl. 18 Wistar rats were randomly divided into CAP group,CAP/MMT group(MMT as carrier)and CAP/PEG1000/MMT group(PEG1000/MMT as carrier)and ig given corresponding drugs,that equal to 200 mg/kg of CAP. Blood sample was respectively taken 15,30,60,90,120,180,240,300 and 360 min after the administration of drugs,and plasma was isolated and added with internal standard ferulic acid. The concentration of the drug in the plasma was determined by HPLC fol-lowing protein precipitation with methanol,based on which the pharmacokinetic parameters were calculated by 3p97 software. RE-SULTS:The linear range of CAP was 0.054 9-4.390 0 μg/ml (r=0.998 2) with the method recovery of 98.2%-102.1%(RSD=1.50%-3.29%, n=5) and absolute recovery of 76.2%-78.9%(RSD=2.29%-2.99%, n=5). In the above-mentioned three groups,t1/2 were(1.11±0.32),(1.57±0.32)and(1.62±0.10)h;cmax were(2.91±0.36),(0.91±0.23)and(0.91±0.14)μg/ml;AUC0-6 h were (8.70 ± 1.79),(3.76 ± 0.27) and (3.73 ± 0.25)μg·h/ml;and tmax were (0.97 ± 0.20),(1.55 ± 0.47) and (1.50 ± 0.07) h,respectively. There was no significant difference in the pharmacokinetic parameters between the CAP/MMT group and CAP/PEG1000/MMT group(P>0.05). CONCLUSIONS:The method is reliable and simple,and can be used for pharmacokinetic study of CAP/PEG1000/MMT in rats. MMT and PEG1000/MMT compound can prolong CAP acting time in the body.
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Objective: To establish the cardio-renal syndrome (CRS) model by coarctation of abdominal aorta (CAA) with renal ischemia reperfusion injury (RIRI), and to observe the mRNA expression of pro-renin receptor [(P)RR] in experimental rats. Methods: A total of 42 Wistar rats were randomly divided into 4 groups: Sham group, CAA group, RIRI group and CAA+RIRI group.n=10 in each group, 2 rats died during the modeling and all animals were treated for 16 weeks. Blood levels of BNP, creatinine (Cr), urea nitrogen (BUN), the activity of rennin, the contents of angiotensin-I (AT-I), AT-II and aldosterone were examined by laboratory test. The diastolic end inter-ventricular septum thickness (DEIVST), DELVPT, LVEF, ventricular weight index (VWI) and cardiac weight index were detected by small animal echocardiography. The histological changes of myocardium and kidney tissue were measured by HE staining, and the mRNA expressions of pro-renin receptor in myocardium and kidney tissues were measured by RT-PCR. Results: Compared with Sham group, blood levels of BNP were increased in the other 3 groups,P0.05. Compared with CAA group, CAA+RIRI group had more obvious changes of DEIVST and LVEF,P<0.01. Compared with RIRI group, CAA+RIRI group had more obvious ventricular hypertrophy, higher VWI and cardiac weight index, allP<0.05. HE staining presented that CAA+RIRI group had broadening of myocardial cell bundle space, decreased left renal index, severe tubular atrophy and partial glomerular atrophy. RT-PCR demonstrated that compared with Sham group, the mRNA expressions of pro-renin receptor in myocardium and kidney tissues were decreased in the other 3 groups. Conclusion: Combined CAA+RIRI method may damage the cardial and renal tissues at the same time which was more severe than either CAA or RIRI. While CAA+RIRI model has better controllability and higher consistency that provides a methodological reference for pro-renin receptor in treating CRS in experimental rat’s model.