1.The changes of β-arrestin 2 and microtubule-associated protein light chain 3 in renal tissue of rats with renal ischemia reperfusion injury
Manman CHU ; Yubin WU ; Yue DU
Chinese Pediatric Emergency Medicine 2017;24(2):137-143
Objective To investigate the expression of β-arrestin2 and microtubule-associated pro-tein light chain(LC)3 in renal of rat with acute renal ischemia reperfusion injury,and to analyze the relation-ship between them and renal injury. Methods Fifty-four male SD rat(3-4 weeks old) were randomly divid-ed into three groups:control group,sham group,acute ischemic reperfusion injury group. We established the acute renal ischemia reperfusion injury model through removing the right kidney and clamping the left renal for 45 minutes with noninvasive arterial clip. We obtained the kidney and blood samples respectively at 12 h, 24 h,36 h,48 h,72 h,96 h after the surgery. Expressions ofβ-arrestin2 and LC3 protein were detected by the immunohistochemistry method and Western blot method. The renal function and morphological changes were assessed. Results Compared with control group and sham group,the serum creatinine and kidney pathologi-cal grading of acute ischemia reperfusion injury group obviously rised. The kidney injury was the most serious at the 24 h after acute ischemic reperfusion injury. The expressions of β-arrestin2 and LC3 were little in the control group and sham group. However,the expressions of these two indicators were obviously higher and reached the peak at the 12 h after acute ischemia reperfusion injury. All these results suggested that the chan-ges of these two indicators were anterior to the histopathological changes. The expressions ofβ-arrestin 2 and LC3 protein were in positive correlation with the kidney injury(r=0. 821,P<0. 05;r=0. 913,P<0. 05). Conclusion In the acute renal ischemia-reperfusion injury,β-arrestin2 may be as a kind of upstream regula-tory protein involving in the kidney pathological process through the regulation of the autophagy.
2.Preparation and in vitro evaluation of borneol and folic acid co-modified doxorubicin loaded PAMAM drug delivery system.
Jingjing LI ; Manman GUO ; Shunping HAN ; Yue SUN ; Weidong FEI ; Xiuiing XU ; Fanzhu LI
Acta Pharmaceutica Sinica 2015;50(7):899-905
A novel targeting drug carrier (FA-BO-PAMAM) based on the PAMAM G5 dendrimer modified with borneol (BO) and folic acid (FA) molecules on the periphery and doxorubicin (DOX) loaded in the interior was designed and prepared to achieve the purposes of enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. 1H NMR was used to confirm the synthesis of FA-BO-PAMAM; its morphology and mean size were analyzed by dynamic light scattering (DLS) and transmission electron microscope (TEM). Based on the HBMEC and C6 cells, cytotoxicity assay, transport across the BBB, cellular uptake and anti-tumor activity in vitro were investigated to evaluate the properties of nanocarriers in vitro. The results showed that the nanocarrier of FA-BO-PAMAM was successfully synthesized, which was spherical in morphology with the average size of (22.28 ± 0.42) nm, and zeta potential of (7.6 ± 0.89) mV. Cytotoxicity and transport across the BBB assay showed that BO-modified conjugates decreased the cytotoxicity of PAMAM against both HBMEC and C6 cells and exhibited higher BBB transportation ability than BO-unmodified conjugates; moreover, modification with FA increased the total uptake of DOX by C6 cells and enhanced the cytotoxicity of DOX-polymer against C6 cells. Therefore, FA-BO-PAMAM is a promising nanodrug delivery system in employing PAMAM as a drug carrier and treatment for brain glioma.
3.Study regional homogeneity and low frequency amplitude of brain resting state functional magnetic resonance imaging in patients with depression
Bing ZHAO ; Xilin WANG ; Manman CHEN ; Ying LIU ; Han ZHANG ; Jinmin LIAO ; Yue GAO
Chinese Journal of Behavioral Medicine and Brain Science 2016;25(11):986-991
Objective To explore the abnormally functional brain regions of female patients with depression by resting state functional magnetic resonance imaging (fMRI),and analyze the correlation with the severity of depressive symptoms.Methods 32 female patients diagnosed with depressive disorder and 40 matched healthy controls completed resting state fMRI scans.The whole brain's regional homogeneity (ReHo) and amplitude of low-frequency fluctuation(ALFF) were calculated,and the correlation analysis be tween ReHo and ALFF of brain regions with significant difference and the severity of depressive symptoms was conducted.Results Compared with control group,the left precuneus/left cuneus (MNI:-18,-81,45),bilateral precentral gyrus (MNI:-58,-5,35 and 57,-6,33),left inferior parietal lobule (MNI:-42,-36,45) and right inferior temporal gyrus(MN1:60,-45,-18) (P<0.05,corrected by AlphaSim)in the case group showed significantly decreased ReHo,with statistical significance.Compared with control group,the left cuneus(MNI:-3,-87,30),right inferior temporal gyrus(MNI:60,-48,-18) and left precentral gyrus(MNI:-63,-3,26) (P<0.05,corrected by AlphasSim)in the case group showed significantly decreased ALFF.The ReHo in the right inferior temporal gyrus was negative correlated with the HAMD-17 total score and retarda tion factor(r=-0.484,P=0.017;r=-0.408,P=0.048),the ALFF in the right inferior temporal gyrus was positively correlated with weight factor(r=0.574,P=0.003),and negative correlated with the number of depressive episodes(r=-0.416,P=0.043).Conclusion Female with depression in resting state have several abnormally functional brain regions and the extent of damage is correlated with the severity of depressive symptoms.Combination of the two parameters may yield a more comprehensive pathophy-siological mechanism for depressive disorder.
4.Role of STING signaling pathway in CORM-3-induced reduction of hepatocyte pyroptosis and apoptosis in a rat model of hepatic ischemia-reperfusion
Weichao ZHENG ; Yulin CHANG ; Yue XIN ; Yan LI ; Jing BAI ; Manman QI ; Limin ZHANG
Chinese Journal of Anesthesiology 2022;42(10):1197-1201
Objective:To evaluate the role of stimulator of interferon genes (STING) signaling pathway in carbon monoxide (CO)-releasing molecule-3 (CORM-3)-induced reduction of hepatocyte pyroptosis and apoptosis in a rat model of hepatic ischemia-reperfusion.Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 9-11 weeks, weighing 320-380 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (S group), ischemia-reperfusion group (IR group), CORM-3 group (C group) and STING agonist ADU-S100 group (A group).Hepatic ischemia-reperfusion injury models were developed by reversible ligation of left middle hepatic artery, portal vein and bile duct branches for 45 min, followed by reperfusion in anesthetized animals in IR, C and A groups.In group C, CORM-3 4 mg/kg was injected into the femoral vein immediately after reperfusion.The equal volume of normal saline containing dimethyl sulfoxide was injected into the femoral vein in S, IR and A groups.At 1.5 h after injection into the femoral vein, ADU-S100 10 mg/kg was intraperitoneally injected in A group, and the equal volume of normal saline was given instead in S, IR and C groups.The serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations were determined at 3 h of reperfusion.The rats were sacrificed at 12 h of reperfusion, and liver tissues were collected for determination of the content of CO (by colorimetry), expression of interleukin-1beta (IL-1β), IL-18, Bcl-2, Bax, interferon regulatory factor 3 (IRF3), phosphorylated IRF3 (p-IRF3), STING, NOD-like receptor protein 3 (NLRP3), aspirin D (GSDMD) and activated caspase-1 (by Western blot), and pyroptosis and apoptosis rates of hepatocytes (by immunofluorescence staining).The liver injury was scored. Results:Compared with group S, the serum ALT and AST concentrations, liver injury score, CO content, and pyroptosis and apoptosis rates of hepatocytes were significantly increased, and the expression of IL-1β, IL-18, p-IRF3, STING, NLRP3, GSDMD and activated caspase-1 was up-regulated, and the Bcl-2/Bax ratio was decreased in group IR ( P<0.05).Compared with group IR, the serum ALT and AST concentrations, liver injury score, and pyroptosis and apoptosis rates of hepatocytes were significantly decreased, the CO content was increased, the expression of IL-1β, IL-18, p-IRF3, STING, NLRP3, GSDMD and activated caspase-1 was down-regulated, and the Bcl-2/Bax ratio was increased in group C ( P<0.05).Compared with group C, the serum ALT and AST concentrations, liver injury score, and pyroptosis and apoptosis rates of hepatocytes were significantly increased, the CO content was decreased, the expression of IL-1β, IL-18, p-IRF3, STING, NLRP3, GSDMD and activated caspase-1 was up-regulated, and the Bcl-2/Bax ratio was decreased in group A ( P<0.05). Conclusions:The mechanism by which CORM-3 attenuates hepatocyte pyroptosis and apoptosis may be related to the inhibition of activation of STING signaling pathway in a rat model of hepatic ischemia-reperfusion.
5.Efficacy of group play therapy on cognitive function and negative symptoms in hospitalized female patients with schizophrenia
Manman YUE ; Rui MA ; Yuanxiong WU ; Rui WANG ; Yanhai WU ; Jinling WU ; Shu CUI
Sichuan Mental Health 2024;37(3):232-236
BackgroundSchizophrenia patients are often accompanied by negative symptoms and severe cognitive impairment, but effective interventions intended to alleviate such condition are currently limited. Existing researches on group play therapy for schizophrenia is still in its initial stages, and such therapy has the potential to contribute to symptoms improvement. ObjectiveTo explore the efficacy of group play therapy on improving cognitive function and negative symptoms in hospitalized female patients with schizophrenia, so as to provide references for clinical intervention in such group. MethodsThis study involved 40 female patients with schizophrenia who received inpatient treatment at the Third People's Hospital of Fuyang from April 2022 to May 2023 as well as met the diagnostic criteria of the International Classification of Diseases, tenth edition (ICD-10). They were divided into study group (n=20) and control group (n=20) according to the random number table method. Both groups received routine treatment, and the study group received 10 sessions of group play therapy for 5 weeks on the basis. At baseline, Scale for Assessment of Positive Symptoms (SAPS), Scale for Assessment of Negative Symptoms (SANS), Self-rating Depression Scale (SDS), Nurses' Observation Scale for Inpatient Evaluation (NOSIE), and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used for assessment. Post-therapy evaluation was conducted by using SAPS, SANS and RBANS. Patients' baseline SAPS scores, SANS scores, RBANS total scores, and various factor scores of RBANS were used as covariates, and covariance analysis was adopted to compare the scores of each scale between the two groups after treatment. ResultsA total of 39 patients went through the whole study. Results of covariance analysis showed that the SANS score of study group was lower than that of control group, while several scores of RBANS (including total score, immediate memory factor score, speech function factor score and attention factor score) were all higher than those in control group. Significant difference was observed between two groups in scores of both scales above (F=13.408, 10.331, 4.932, 9.967, 10.010, P<0.05 or 0.01). ConclusionGroup play therapy may help improve negative symptoms and cognitive function in hospitalized female patients with schizophrenia. [Funded by Research project of Fuyang Municipal Health Commission (number, FY2021-147)]