2.Progress and prospect in the clinical translation of cancer nanomedicine
Acta Pharmaceutica Sinica 2022;57(1):134-141
Nanotechnology has shown broad application prospects in the diagnosis and treatment of cancer. Currently, nearly 80 cancer nanomedicines are under clinical investigation, and many have been approved with enhanced anti-tumor efficacy and decreased side effects. However, the presence of various barriers in related basic research, process control and clinical trials lead to extremely low translation rate. From the perspective of clinical commercialization, we summarized the progress, clinical status, challenges and opportunities of cancer nanomedicine, and presented a cutting-edge prospect on the rational design of nanomedicine and clinical trial strategies.
4.Effects of fluoride on expressions of TGF-? and Smad2/3 in fibroblasts and osteoblasts
Yizhuo ZHAO ; Ling QI ; Hui XU ; Ling JING
Journal of Jilin University(Medicine Edition) 2006;0(06):-
Objective To explore the effects of fluoride with different doses on the expressions of TGF-? and Smad2/3 in fibroblast and osteoblast at different periods.Methods Fibroblasts and osteoblasts were exposed to different concentrations of fluoride(0,0.0001,0.001,0.1,1,10 and 20 mg?L~(-1)).The levels of TGF-? protein and Smad2/3 at 2,4,24,48 and 72 h after treatment were measured by using ELISA method.The expression of TGF-? mRNA was tested with RT-PCR method.Results In fibroblasts,the contents of TGF-? protein were decreased in the groups of 0.001,0.1,1,10 and 20 mg?L~(-1) F~-at the time of 2 h and in the groups of 1.0001,0.001,0.1,10 and 20 mg?L~(-1) at the time of 4 h(P
5.Therapeutic Benefit of TH,AADC,and GCH-I Genes for Parkinson's Disease in Rat Model
Ling-Ling LU ; Huan-Ying ZHAO ; Jun WU ; Hui YANG ;
China Biotechnology 2006;0(02):-
Parkinson's disease(PD) is a common neurodegenerative disorder with no effective protective treatment,characterized by a massive degeneration of dopaminergic neurons in the substantia nigra(SNpc) and the subsequent loss of their projecting nerve fibers in the striatum.The major neurochemical manifestation of this disorder is the loss of the neurotransmitter dopamine(DA) in the striatum as a result of the progressive degeneration of the dopaminergic neurons in the substantia nigra.There have been significant progresses in recent years reporting on the use of mesenchymal stem cells(MSCs)in gene therapy,with specific application towards PD.MSCs,a kind of multipotent adult progenitor cells,are considered as a useful vehicle for cell and gene therapy because of their multiple differentiation potentiality and self-transplantation.The present study was focused on treating rat model of PD using human tyrosine hydroxylase gene(hTH),human aromatic L-amino acid decarboxylase gene(hAADC) and human GT Pcyclohydrolase I gene(hGCH-I) engineered MSCs,in order to provide a better understanding about the application of these cells in the therapeutic benifit of PD.The gene of hTH,hAADC and hGCH-I were introduced via recombinant adeno-associated virus(rAAV) infection into the MSCs in vitro.The genetically modified MSCs expressing hTH,hAADC and hGCH-I were transplanted into the striatum of PD rat models.The behavior,the nigra-striatal level of DA and its metabolite were detected.The results of present study were shown as follows:hTH,hAADC,hGCH-I and LacZ gene were transfected into MSCs with adeno-associated virus vectors.The HEK293 packaging cells(ATCC) were transfected with the plasmids of pAAV-hTH,pAAV-hAADC,pAAV-hGCH-I,pAAV-LacZ,pAAV-RC,pHelper by using calcium phosphate precipitation.Titer was detected using HT1080 cells.Viral particles were collected and used to infect MSCs.The purified modified MSCs expressing the three kinds of genes were selected separately and were grafted in the striatum of the PD model rats in the lesion side.The MSCs genetically modified suvived well 12 weeks after transplantation.The improvements of the behavior were observed every week after transplantation.Compared with the control group,the rounds of asymmetric rotation after apomorphine administration decreased in the groups double or triple genes engineered MSCs grafted(p
6.The Influence of ?-Synuclein Overexpression on Mitochondrial Membrane Structure with Atomic Force Microscopy
Chun-Li ZHAO ; Yuan-Gang ZHU ; Chun-Li DUAN ; Ling-Ling LU ; Ling ZHANG ; Hui YANG ;
China Biotechnology 2006;0(11):-
Objective:To identify the effect of ?-synuclein overexpression on mitochondrial membrane structure with atomic force microscopy. Methods:?-syn expression was mediated by AAV (adeno-associated viral vector) and Recombinant AAV/?-syn and AAV/LacZ viral particles were stereotaxically injected in the left side of rat substantia nigra (SN) for rat model of ?-synuclein overexpression. Mitochondria were isolated from rats SN of Brain. Mitochondria were analysis with JC-1 staining,atomic force microscopy and Western blot. Results:By 16 weeks post-infection of AAV-?-syn,the level of ?-syn increased about 2 times in mitochondrial fraction with Western blot and mitochondrial membrane potential (??) decreased with JC-1 staining. Furthermore,mitochondria swelling and porous like structure formed on the mitochondrial membrane with atomic force microscopy. Conclusion:The data suggested that ?-syn could accumulate in mitochondria,might form mitochondrial membrane pores and lead to ?? decreases. ?-syn might lead to mitochondrial dysfunction in Parkinson's disease.
7.Study on the Role of ?-synuclein in Mitochondria Dysfunction Caused by Small Dosage Rotenone
Ling-Ling LU ; Yuan LIANG ; Chun-Li DUAN ; Chun-Li ZHAO ; Huan-Ying ZHAO ; Hui YANG ;
China Biotechnology 2006;0(12):-
Mitochondrial dysfunction has been implicated in the aetiology of sporadic Parkinson's disease but its role in the disease mechanism remains unclear.To investigate the effect of synuclein on mitochondrial dysfunction induced by rotenone.The human dopaminergic SH-SY5Y cells were used as a cell model.The cells over-expressed the wild-type ?-synuclein were treated with complex I inhibitor rotenone.The cell viability,complex I activity,Mitochondrial swelling and O2-content were tested at different time point-1w,2w,4w after rotenone treated.CCK-8 test results showed that the cell viability of overexpressed ?-synuclein(SH-SY5Y-Syn)was much lower than the control group(SH-SY5Y-Ctr).After administrating with rotenone about 1w or 2w the cell viability of SH-SY5Y-Syn became higher than that of SH-SY5Y-Ctr.On the 4th week the results were contrary to the first 2 weeks.Similar results were got when test the mitochondrial function.In the first 2 weeks after roteoone administrating,the mitochondrial function of SH-SY5Y-Syn was better than that of SH-SY5Y-Ctr.This suggest that the ?-synuclein could protect the mitochondrial against the injury induced by rotenone in the early stage-1w,2w,while this effect disappeared in the final stage-4w.
9.Inhibitory cells proliferation and induce cells apoptosis by TPT on HL-60 cell by c-myc
Fang WANG ; Ling SUN ; Hui SUN ; Xiaoping LE ; Xiaoqiang ZHAO
Journal of Leukemia & Lymphoma 2008;17(3):172-174
Objective The effects of TPT on the induction of apoptosis of leukemia cells and the regulation of c-myc in mRNA and protein level. Methods RT-PCR method was adopted to examine the expressions of the genes and immune histochemistry for the proteins of c-myc in HL-60 cells treated with TPT of optimal concentration and time. Results After HL-60 cells by TPT of 0.15 μmol/L for 12 h, the expression of c-myc mRNA decreased markedly assayed by RT-PCR. There was a significant difference between the TPT group and the control group(0.17±0.03 vs 1.11±0.25, P <0.05), expressive c-myc protein decreased assayed by evidently immunohistochemistry. The percentage of positive cells expressing c-myc protein was a significant difference between the TPT treated group and the control group (19.67 % vs 68.33 %, P<0.05). Conclusion TPT down-regulates endogenic c-myc mRNA and c-myc protein in HL-60 cells.
10.Bacteria Contens in Air of Tuberculosis Wads Before and After Use:A Comparative Study
Xiufeng ZHANG ; Hui ZHAO ; Huiquan XU ; Xiuling DU ; Ling YAN
Chinese Journal of Nosocomiology 2009;0(15):-
OBJECTIVE To detect the condition of bacteria of the air in wards of our hospital in order to reduce the possibility of air spread. METHODS Ten tuberculosis wards were chosen at random for study.Detected the bacteria content of the air in wards used before and after respectively and analysed the results. RESULTS The average of backgroud bacteria was 164 CFU/m 3 before the wards were used.Two years later,the average of bacteria increased to 682 CFU/m 3.The ratio was 1∶3:2 on average.There were significant differences between them. CONCLUSIONS Humen are the main facters that make the air polluted in these wards.The bacteria content will decline by good environment cleaning sanitation,ventilation and strengthening steriling management.Infection will decline in the hospital.