Mesoporous silica nanoparticles as drug carrier have become the new hot point in the field of biomedical application in recent years. This review focuses on the more recent developments and achievements on experimental design aspect of mesoporous silica nanoparticles with cancer diagnosis and therapy. The key advances of functionalization strategies of mesoporous silica nanoparticles with controlled release, tumor targeting and overcoming multidrug resistance are discussed in particular. Mesoporous silica nanoparticles as unique delivery systems have the potential to provide significantly a sound platform for cancer theranostic application.

OBJECTlVE To investigate the antidepressant effect and reIated mechanism of the totaI fIavonoids extract parts( Iicorice fIavonoids,LF)from Glycyrrhiza uralensisFisch. cuItivated IocaIIy in Ningxia. METHODS Forced swimming test( FST)and taiI suspension test( TST)were adopted to study the antidepressant pharmacoIogicaI effect in the acute stress-induced depression modeI in mice. The Km mice were intragastricaIIy administered with LF(5,30 and 180 mg·kg-1 )once daiIy,for 21 con-secutive days. One hour after the first,seventh and Iast administrations,the mice were submitted to FST by recording the immobiIity period within the Iast 4 min of the totaI 6 min in both tests and the resuIts were expressed as decrease in immobiIity period with respect to vehicIe controI. In TST,the other group of Km mice was used to evaIuate the antidepressant effect in same protocoI. In the antagonism of reserpine-induced symptoms test( ART),ICR mice were administered intragastricaIIy with LF( 50,150 and 400 mg·kg-1 )once daiIy for 7 consecutive days. One hour after the Iast administration,the mice received reserpine(4 mg·kg-1 ,ip),and ptosis or akinesia was measured 1 h after reserpine injection whiIe rectaI temperature was measured 4 h after the reserpine injection respectiveIy. The same protocoI was adopted in yohimbine toxicity potentiation test(YTT)as in ART. Thirty minutes fter the Iast adminis-tration,the mice received the threshoId IethaI dosage of yohimbine(30 mg·kg-1 ,sc)respectiveIy,and the death number of the mice was caIcuIated in 24 h after the yohimbine administration. In the 5-hydroxy-L-tryptophan(5-HTP)induced head-twitches test(HTT)in mice,after being administered intragastricaIIy with LF(50,150 and 400 mg·kg-1 )once daiIy for 7 consecutive days,the mice received pargiIine (100 mg·kg-1 ,ip)the next day,and 30 min Iater,5-HTP(10 mg·kg-1 ,ip)was intraperitoneaIIy injec-ted to induced the head twitch respectiveIy,and the times of head twitch in a 30 min period after 5-HTP treatment were observed at 6 time points. After HTT,the mice were sacrificed quickIy,and the mono-amine oxidase(mAO)activity in the brain cortex,hippocampus and thaIamus was examined to evaIuate the antidepressant effect of fIavonoids with mAO inhibition. RESULTS Compared with the vehicIe controI,LF significantIy decreased the immobiIity period in both FST and TST(P﹤0.05). LF(50,150 and 400 mg·kg-1 )antagonized the ptosis and akinesia symptoms respectiveIy in 1 h after reserpine administration( P ﹤ 0. 05 ), but faiIed to antagonize hypothermia produced 4 h after reserpine administration. AIso,at the same dosage,LF did not synergeticaIIy produce the enhancement of death by subcutaneous injection of yohimbine at the threshoId IethaI dosage. LF(150 and 400 mg·kg-1 )couId significantIy and synergeticaIIy increase 5-HTP induced head-twitches response(P﹤0.05),but LF couId not promote mAO activity in the cortex,hippocampus and thaIamus at the same dosage. CONCLUSlON LF exerts antidepressant-Iike effect on the modeI of acute despair test. The mechanism might be reIated to direct enhancement of the serotonergic neuraI function in the brain.

OBJECTIVETo investigate the epileptic seizure-like effect of Sophora alkaloid sophoridine on electroencepholography (EEG) and its possible characteristic and the mechanism of the seizure-like effect.

METHODChronic electron implantation was employed for the intracranial electroencepholography (IEEG) recording in rat, and the traditional anti-seizure drugs were for the mechanism study in mice.

RESULTCompared with the medial perforant path (PP) area and the temporal cortex (TC), the granule cells in hippocampus dentate gyrus (DG) area is more sensitive in the kindling effect by sc sophoridine. Under-threshold hypnotic dosage of diazepam and the hypnotic dosage of pentobarbital sodium can block the sophoridine kinded seizure in mice, but the phenytoin sodium can not block the seizure, also the dosage of it can block the maximal electroconvulsive shock (MES) seizure.

CONCLUSIONSophoridine-induced synchronous oscillations in the hippocampus could elicit the generation and development of seizure. And the hippocampus might play the crucial role and be the original part of the seizure. Sophoridine kinded seizure might belong to clonic seizures, and the diazepam is the ideal agent for the treatment.

Alkaloids ; chemistry ; pharmacology ; Animals ; Epilepsy ; chemically induced ; metabolism ; Hippocampus ; drug effects ; metabolism ; Male ; Mice ; Quinolizines ; chemistry ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sophora ; chemistry

Objective:To investigate the inhibitory effect of ferulic acid on the retina of diabetic mice and high glucose-induced human retinal pigment epithelium (RPE) cell injury and the mechanism.Methods:Thirty 8-week-old SPF male type 2 diabetic db/db mice were selected and divided into a model group and a ferulic acid group by the random number table method, with 15 mice in each group.Another 15 db/m mice of the same age were selected as a control group.The model and control groups received normal saline (5 ml/kg) by gavage daily, and the ferulic acid group received ferulic acid solution (0.05 g/kg) by gavage daily.After two months of treatment, the mice were sacrificed and the eyeballs were removed.The morphological changes of mouse retinal tissues were observed by hematoxylin-eosin staining.The fluorescence intensity and expression levels of mitochondrial calcium uniporter (MCU), p38 mitogen-activated protein kinase (p38 MAPK) and phosphorylated p38 MAPK (p-p38 MAPK) in mouse retinal tissues were detected by immunofluorescence staining and Western blot.Human RPE cells were divided into control group, dimethyl sulfoxide (DMSO) group, high glucose group and high glucose+ ferulic acid group.The control group received no treatment, and the other cell groups were cultured with the corresponding reagents for 24 hours.The reactive oxygen (ROS) level of RPE cells in each group was detected with the ROS detection kit.The mitochondrial membrane potential level of RPE cells was detected with the a mitochondrial membrane potential detection kit (JC-1).The MCU and microfilament fluorescence intensity of RPE cells were detected with the a microfilament green fluorescent probe.To explore the regulatory relationship between MCU, p38 MAPK and p-p38 MAPK, the MCU protein level was silenced and overexpressed by lentivirus transfection technology.The fluorescence intensity and expression levels of MCU, p38 MAPK and p-p38 MAPK proteins in RPE cells were detected by immunofluorescence staining and Western blot.The use and feeding of experimental animals followed the 3R principle and the Statement of the Association for Research in Vision and Ophthalmology on the Use of Animals in Ophthalmology and Vision Research.This study protocol was approved by the Ethics Committee of Ningxia Eye Hospital, People's Hospital of Ningxia Hui Autonomous Region (No.2019085).Results:The intercellular space of the outer nuclear layer, inner nuclear layer and ganglion cell layer of the retinal tissue in the model group was increased and the cell arrangement was disordered compared with the control group, and the retinal tissue in the ferulic acid group was significantly improved.Compared with the control group, the fluorescence intensity of MCU, p-p38 MAPK and MCU+ p-p38 MAPK protein of mouse retinal tissue in model group and ferulic acid group was significantly increased (all at P<0.05).Compared with the model group, the fluorescence intensity of MCU, p-p38 MAPK and MCU+ p-p38 MAPK protein of mice retinal tissue in ferulic acid group was significantly decreased (all at P<0.05).Compared with the control group, the relative expression levels of MCU, p38 MAPK and p-p38 MAPK proteins of mouse retinal tissue in model group were significantly increased (all at P<0.05).Compared with the model group, the relative expression levels of MCU, p38 MAPK and p-p38 MAPK proteins of mice retinal tissue in ferulic acid group were significantly decreased (all at P<0.05).The ROS fluorescence intensities in the control group, DMSO group, high glucose group and high glucose+ ferulic acid group were 0.22±0.02, 0.22±0.03, 0.30±0.02 and 0.24±0.02, respectively, and the overall difference was statistically significant ( F=7.845, P<0.01).The ROS fluorescence intensity was significantly higher in the high glucose group than in the control and DMSO groups, and it was significantly lower in the high glucose+ ferulic acid group than in the high glucose group (all at P<0.05).The mitochondrial membrane potential was significantly lower in high glucose group and high glucose+ ferulic acid group than in control and DMSO groups, and significantly higher in high glucose+ ferulic acid group than in high glucose group (all at P<0.05).Compared with the control group and DMSO group, the fluorescence intensity of MCU was higher in the high glucose group, accompanied by the decrease and thinning of cell microfilaments, and the fluorescence intensity of MCU protein was significantly decreased in high glucose+ ferulic acid group, with the number of microfilaments increased significantly.Compared with the control group and DMSO group, the fluorescence intensity and relative expressions of MCU, p38 MAPK and p-p38 MAPK proteins were significantly increased in the high glucose group (all at P<0.05).Compared with the high glucose group, the fluorescence intensity and relative expressions of MCU, p38 MAPK and p-p38 MAPK proteins were significantly decreased in the high glucose+ ferulic acid group (all at P<0.05).Compared with the control group and the empty vector group, the relative expressions of MCU, p38 MAPK and p-p38 MAPK proteins were significantly increased in the MCU overexpression group and significantly decreased in the MCU shRNA group and the MCU overexpression+ ferulic acid group (all at P<0.05).Compared with MCU overexpression group, the relative expressions of MCU, p38 MAPK and p-p38 MAPK proteins were significantly decreased in MCU shRNA group and MCU overexpression+ ferulic acid group, and the differences were statistically significant (all at P<0.05). Conclusions:Ferulic acid can regulate oxidative stress and mitochondrial dysfunction, thereby ameliorating retinal damage and high glucose-induced RPE cell injury in diabetic mice, which may play a protective role through MCU and p38MAPK signaling pathways.