2.Recent progress of non-viral vector polyethylenimine in the application of gene delivery
Cui-ping JIANG ; Yuan WANG ; Hai-yan XIAO ; Hai-yue ZHAO ; Qiang LIU
Acta Pharmaceutica Sinica 2020;55(12):2869-2882
In recent years, non-viral gene vectors have attracted great attention for efficient gene delivery due to the advantages, including low toxicity, low immunogenicity and simple preparation. Polyethylenimine (PEI) is one of the typical non-viral gene carriers that have been widely utilized for gene delivery owing to its superior capabilities in gene compression and buffering capacity. This article discusses the processes of gene delivery and the barriers of PEI-based carrier during the gene delivery, such as low biocompatibility, cytotoxicity, lack of specific targeting and insufficient gene release, etc
3.Effect of Ginkgo biloba Tablet on the Expression of Scavenger Receptor A of the Aortic Wall in Atherosclerotic Rats.
Gui-yue ZHU ; Wei ZHU ; Ling-yun PAN ; Xiao-jing MA ; Hai-tao YUAN ; Guang YANG
Chinese Journal of Integrated Traditional and Western Medicine 2016;36(4):449-453
OBJECTIVETo observe the expression of Ginkgo biloba Tablet (GbT) on scavenger receptor A (SRA) of the aortic wall and changes of serum inflammatory factors in atherosclerotic rats, and to explore its new mechanism for fighting against atherosclerosis (AS).
METHODSTotally 45 male Wistar rats were randomly divided into the control group, the model group, the GbT group, 15 rats in each group. Levels of blood glucose, blood lipids, blood calcium, serum C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (slCAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in all rats. The expression of SRA in the aortic wall of atherosclerotic rats was observed by immunohistochemical assay. The correlation between the expression of SRA and levels of in-flammatory factors was also observed.
RESULTSCompared with the control group, blood glucose and blood calcium obviously increased (P < 0.05); levels of TG, TC, and LDL-C were significantly elevated (P < 0.01); neointimal areas were significantly thickened, increased intima percentage was significantly enlarged, narrowed lumen index was significantly reduced; levels of CRP, sICAM-1, and sVCAM-1 were significantly elevated in the model group (all P < 0.01). Compared with the model group, blood glucose and blood calcium obviously decreased (P < 0.05); levels of TG, TC, and LDL-C significantly decreased (P < 0.01) in the GbT group. Aortic lumens were obviously narrower in the model group than in the GbT group (P < 0.05). SRA expressed at the aortic wall. The aforesaid 3 indices were significantly improved in the GbT group than in the model group (P < 0.01). Serum levels of CRP, sICAM-1, and sVCAM-1 were significantly decreased in the GbT group than in the model group (P < 0.01). Serum levels of CRP, sICAM-1, and sVCAM-1 were positively correlated with the percentage of SRA positive expression area (r = 0.701, 0.604, 0.581, all P < 0.01).
CONCLUSIONSSerum levels of inflammatory factors in atherosclerotic rats were elevated, and the expression of SRA in the aortic wall was enhanced. The expression of SRA was closely correlated with serum levels of inflammatory factors. GbT could decrease serum levels of inflammatory factors and inhibit the expression of SRA.
Animals ; Aorta ; drug effects ; metabolism ; Atherosclerosis ; drug therapy ; Blood Glucose ; analysis ; C-Reactive Protein ; analysis ; Calcium ; blood ; Drugs, Chinese Herbal ; pharmacology ; Ginkgo biloba ; chemistry ; Intercellular Adhesion Molecule-1 ; blood ; Lipids ; blood ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Scavenger Receptors, Class A ; metabolism ; Tablets ; Vascular Cell Adhesion Molecule-1 ; blood
4.Effect of nerve growth factor on denervated bone fracture healing in rats
Cheng MA ; San-Huai GOU ; Hai-Jun XIAO ; Yue-Ping OUYANG ; Yan LIU ; Fang HE ;
Academic Journal of Second Military Medical University 1985;0(05):-
Objective:To study the effect of nerve growth factor(NGF)on bone fracture healing of inflicted T_(10)spinal cord injury(SCI)complicated with tibia fracture in rats.Methods:Totally 120 rats were randomly divided into tihia fracture group (F group,n=40),T_(10)SCI+tibia fracture group(FS group,n=40),and T_(10)SCI+tibia fracture+NGF group(FSN group,n=40).Four weeks later,the fracture sites in the 3 groups were subjected to CT scanning;the maximum transverse diameter of the fracture ends and the gray scales of non-osseous area were measured;the changes of biomechanics property of the fracture ends were determined by three-point bending test;the bone morphometry,bone density,and histomorphology of callus were determined;the expression of OCN was detected by immunohistochemical method;the osteoblast ultrastructure was observed by TEM and the expression ofⅠ,Ⅱtype collagen were examined by Western blotting.Results:The maximum transverse diameter of F group was less than those of FS group(P
5.Immune response after injecting polysaccharide nucleic acid of Bacillus Calmette-Guerin under mucous membrane of bladder in rabbits
Shi-Ping SUN ; Yu-Feng ZHANG ; Xiao-Long YUE ; Hai-Ping WANG ;
Chinese Journal of Cancer Biotherapy 2006;0(05):-
Objective:To investigate the immune response after injecting polysaccharide nucleic acid of Bacillus Calmette-Guerin(BCG-PSN)under the mucous membrane of bladder in rabbits and to search for the most suitable dose of BCG-PSN.Methods:The rabbits were randomly divided into 5 groups:high dose(0.35 mg/ml)BCG-PSN group,mid- dle dose(0.175 mg/ml)BCG-PSN group,low dose(0.0875 mg/ml)BCG-PSN group,BCG(0.35 mg/ml)control group and BCG-PSN(0.35 mg/ml)intra-bladder perfusion control group.T lymphocyte subsets(CD4~+,CD8~+)in the peripheral blood were determined by flow cytometry before and 1 week,2 weeks,1 month and 3 months after the treatment; the levels of IL-2,TNF-?,and IFN-?of peripheral blood were determined by enzyme-linked immunosorbent assay;H-E and Masson staining was used for the pathological examination of the bladder.Results:(1)BCG-PSN injection increased the number of CD4~+ and CD8~+ T lymphocytes in a time- and dose-dependent manner,with the peak numbers appeared 2 weeks after BCG-PSN injection;the numbers restored to the normal levels 3 months after BCG-PSN injection.BCG control group had a similar changing pattern to the BCG-PSN injection group.The number of CD4~+ T cells BCG-PSN perfusion group was significantly lower than that in the high-dose BCG-PSN injection group(P
6.Effects of surface roughness of bone cements on histological characteristics of induced membranes.
Hai-Xiao LIU ; Hua-Zi XU ; Yu ZHANG ; Gang HU ; Yue SHEN ; Xiao-Jie CHENG ; Lei PENG
China Journal of Orthopaedics and Traumatology 2012;25(8):662-666
OBJECTIVETo explore surface roughness of bone cement and surround tissue on histological characteristic of induced membranes.
METHODSBone cements with smooth and rough surface were implanted in radius bone defect, intramuscular and subcutaneous sites of rabbits, and formed induced membranes. Membranes were obtained and stained (HE) 6 weeks later. Images of membrane tissue were obtained and analyzed with an automated image analysis system. Five histological parameters of membranes were measured with thickness,area,cell density,ECM density and microvessel density. Double factor variance analysis was used to evaluate the effect of the two factors on histological characteristics of induced membranes.
RESULTSMembranes can be induced by each kind of bone cement and at all the three tissue sites. In histological parameters of thickness,area and micro vessel,there were significant differences among the membranes induced at different tissue sites (P = 0.000, P = 0.000, P = 0.000); whereas, there were no significant differences in histological parameters of cell density and ECM density (P = 0.734, P = 0.638). In all five histological parameters of membranes, there were no significant differences between the membranes induced by bone cements with different surface roughness (P = 0.506, P = 0.185, P = 0.883, P = 0.093, P = 0.918).
CONCLUSIONSurround tissue rather than surface roughness of bone cements can affect the histological characteristics of induced membranes. The fibrocystic number, vascularity, mechanical tension and micro motion of the surround tissue may be closely correlated with the histological characteristics of induced membranes.
Animals ; Bone Cements ; Female ; Membranes ; cytology ; Rabbits ; Radius ; cytology ; Surface Properties ; Tissue Engineering ; methods ; Tissue Scaffolds
7.Correction of the epicanthal fold and angulus oculi using the Z-epicanthoplasty.
Ding-an LUO ; Yue-qiang ZHAO ; Song-shan WANG ; Hai-xiao ZHOU
Chinese Journal of Plastic Surgery 2007;23(6):491-492
OBJECTIVETo explore a new procedure for aesthetic correction of the medial epicanthal fold aim at the etiopathogenesis.
METHODSThe new Z-epicanthoplasty devise the upper and inferior margin of angle of eye medial as one angle of the Z.
RESULTSFrom 2004 to 2006, 129 patients were treated by using the method. Follow-up 6 to 24 months, all patients were satisfied by eliminating the medial epicanthal fold without obvious scar.
CONCLUSIONSThe method is more effect than traditionally Z-plasty. Our technique is a simple, advanced procedure that can be performed widely.
Adolescent ; Adult ; Blepharoplasty ; methods ; Eyelids ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Young Adult
8.Effects of Different Compatibilities of Ramulus Cinnamomi and Peony in Guizhi Decoction on Diabetic Cardiac Autonomic Neuropathy.
Xiao LI ; Jin-long YANG ; Du-fang MA ; Hai-qing LIN ; Xiang-dong XU ; Hua Jiang YUE
Chinese Journal of Integrated Traditional and Western Medicine 2015;35(6):741-745
OBJECTIVETo observe the preventive effect different compatibilities of Ramulus Cinnamomi (RC) and peony in Guizhi Decoction (GD) on diabetic cardiac autonomic neuropathy (DCAN).
METHODSTotally 60 male rats were randomly divided into 5 groups, i.e., the blank control DM group, the model group, the methycobal group, the 1:1 (RC/peony) Guishao group, the 2:1 Guishao group, and the 1:2 Guishao group, 10 in each group. Rats were pretreated with corresponding drugs for 1 week, and then induced diabetes by intraperitoneal injection of STZ. Drugs were administrated by gastrogavage for 4 more weeks after STZ-injection. Enzyme-linked immunosorbent assay (ELISA) was employed to detect levels of tyrosine hydroxylase (TH), choline acetyltransferase (CHAT), nerve growth factor. (NGF), and ciliary neurotrophic factor (CNTF) in myocardial homogenates.
RESULTSAfter 4-week modeling, body weight (BW) was obviously lower, but blood glucose (BG) was higher in STZ rats than in rats of the blank control DM group. There was no statistical difference in BW or BG among the 5 groups (P >0.05). Compared with the blank control group, TH, TH/CHAT, and NGF in left ventricle and ventricular septum increased, CHAT and CNTF increased in the model group (P < 0.05, P < 0.01). Compared with the model group, TH and TH/CHAT in left ventricle decreased (P < 0.05, P < 0.01), CNTF in left ventricle increased (P < 0.05), CHAT in left ventricle and ventricular septum increased (P < 0.05, P < 0.01) in the methycobal group. TH and TH/CHAT in left ventricle and ventricular septum decreased, CNTF in left ventricle and ventricular septum increased (P < 0.05, P < 0.01), CHAT in left ventricle and ventricular septum increased (P < 0.01), NGF in ventricular septum decreased (P < 0.01) in the 1:1 Guishao group. TH/CHAT in left ventricle decreased (P < 0.01), CHAT and CNTF in left ventricle and ventricular septum increased (P < 0.05, P < 0.01) in the 1:2 Guishao group. Compared with the methycobal group, CHAT in left ventricle decreased, TH and TH/CHAT in left ventricle increased in the 2:1 Guishao group (P < 0.05, P < 0.01). TH and TH/CHAT in ventricular septum decreased (P < 0.05), CHAT and CNTF in left ventricle and ventricular septum increased (P < 0.05, P < 0.01) in the 1:1 Guishao group. Compared with the 1:2 Guishao group and the 2:1 Guishao group, CHAT in left ventricle increased, TH/CHAT in left ventricle decreased, TH and TH/CHAT in ventricular septum decreased, CHAT in ventricular septum increased, CNTF in left ventricle and ventricular septum also increased in the 1:1 Guishao group (all P < 0.01).
CONCLUSIONSSTZ model rats had autonomic neural injury, manifested as lowered vagal nerve activity and hyperactive sympathetic nerves. GD could effectively suppress hyperactive cardiac sympathetic nerves and protect the vagus. Besides, GD (1:1) showed the optimal effect in regulating the balance of cardiac autonomic nerves and could be used in early prevention of DCAN.
Animals ; Blood Glucose ; Choline O-Acetyltransferase ; Diabetic Neuropathies ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Heart ; Heart Ventricles ; Male ; Myocardium ; Nerve Growth Factor ; Paeonia ; Rats ; Tyrosine 3-Monooxygenase
9.N6-Methyladenosine Methyltransferase METTL3 Alleviates Diabetes-Induced Testicular Damage through Modulating TUG1/Clusterin Axis
Yuan TIAN ; Yue-Hai XIAO ; Chao SUN ; Bei LIU ; Fa SUN
Diabetes & Metabolism Journal 2023;47(2):287-300
Background:
The present study investigated the regulatory effects of N6-methyladenosine (m6A) methyltransferase like-3 (METTL3) in diabetes-induced testicular damage.
Methods:
In vivo diabetic mice and high glucose (HG) treated GC-1 spg cells were established. The mRNA and protein expressions were determined by real-time quantitative polymerase chain reaction, Western blot, immunofluorescence and immunohistochemistry staining. Levels of testosterone, blood glucose, cell viability, and apoptosis were detected by enzyme-linked immunosorbent assay, MTT, and flow cytometry, respectively. Molecular interactions were verified by RNA immunoprecipitation and RNA pull-down assay. Histopathological staining was performed to evaluate testicular injury.
Results:
METTL3 and long non-coding RNA taurine up-regulated 1 (lncRNA TUG1) were downregulated in testicular tissues of diabetic mice and HG-treated GC-1 spg cells. METTL3 overexpression could reduce the blood glucose level, oxidative stress and testicular damage but enhance testosterone secretion in diabetic mouse model and HG-stimulated GC-1 spg cells. Mechanically, METTL3-mediated m6A methylation enhanced the stability of TUG1, then stabilizing the clusterin mRNA via recruiting serine and arginine rich splicing factor 1. Moreover, inhibition of TUG1/clusterin signaling markedly reversed the protective impacts of METTL3 overexpression on HG-stimulated GC-1 spg cells.
Conclusion
This study demonstrated that METTL3 ameliorated diabetes-induced testicular damage by upregulating the TUG1/clusterin signaling. These data further elucidate the potential regulatory mechanisms of m6A modification on diabetes-induced testicular injury.
10.Expression of PI3K pathway proteins in refractory epilepsy associated with cortical malformation development.
Hai-chun NI ; Fu-hai SUN ; Yue-shan PIAO ; Xiao-li MA ; De-hong LU
Chinese Journal of Pathology 2012;41(6):391-395
OBJECTIVETo investigate the expression of TSC1, TSC2, p-mTOR, p-4E-BP1, p-p70S6K and p-S6 in refractory epilepsy associated malformation of cortical development (MCD) tissues.
METHODSA total of 43 cases of refractory epilepsy were involved in the study, and all the patients were treated in Xuanwu Hospital during 2005 - 2008, including focal cortical dysplasia type IIa (11 cases) and type IIb (11 cases), tuberous sclerosis complex (10 cases) and ganalioglioma (11 cases), and other 12 cases were used as control. These cases were divided into 7 study groups and immunohistochemical EnVision method was used. To detect the location and intensity of TSC1, TSC2, p-mTOR, p-4E-BP1, p-p70S6K and p-S6 expression in every group. Then the Image-Pro Plus 6.0 image processing and analysis software were used to measure the number, area, integrating absorbance (IA) of positive cells in every samples. The statistical software SPSS 16.0 was used to analyze the data.
RESULTSThe immunolocalization of TSC1 and TSC2 was similar. It could be observed the expression of various levels in the cytoplasm of dysmorphic neurons, balloon cells, giant cells, ganglioglioma cells and normal neurons. TSC1 staining in normal neurons was more notably than others but TSC2 staining in giant cells was weaker than other samples. p-mTOR mainly presented in giant cells, which could also be observed in astrocyte. P-4E-BP1 presented in the cytoplasm and nuclear membrane of balloon cells, giant cells and ganglioglioma cells, the staining of giant cells was stronger than balloon cells, but their staining were weaker than ganglioglioma cells. P-p70S6K mainly expressed in giant cells and less commonly presented in balloon cells. P-S6 typically presented in all abnormal glioneuronal cells and it nearly did not present in the normal neurons of N-CTX group.
CONCLUSIONSPI3K pathway, at least in part, involves in the occurrence of MCD, and may play an important role in the pathogenesis.
Adaptor Proteins, Signal Transducing ; metabolism ; Adolescent ; Adult ; Child ; Epilepsy ; metabolism ; pathology ; Female ; Ganglioglioma ; metabolism ; pathology ; Humans ; Male ; Malformations of Cortical Development ; metabolism ; pathology ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphoproteins ; metabolism ; Ribosomal Protein S6 Kinases ; metabolism ; Ribosomal Protein S6 Kinases, 70-kDa ; metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases ; metabolism ; Tuberous Sclerosis ; metabolism ; pathology ; Tumor Suppressor Proteins ; metabolism ; Young Adult