2.Icariin induces apoptosis of esophageal cancer cell through enhancing Fas-FasL expression activity
Xin JI ; Chong WANG ; Jie LI ; Xiaole YUE
Chongqing Medicine 2016;45(12):1608-1611
Objective To investigate the inhibitory effect of icariin(ICA) on the xenograft tumors growth of esophageal car‐cinoma and to preliminarily investigate its mechanism .Methods The MTT assay and Giemsa staining were applied to detect and observe the in vitro inhibitory effect of ICA on esophagus cancer cell lines Eca‐109 and TE‐13 .The xenograft tumor model of nude mouse esophagus cancer cell was constructed and divided into 3 groups ,6 cases in each group .Each mouse in the experimental group was intraperitoneally injected by ICA 50 mg/kg ;while the control group was injected by the same volume of normal saline and the positive control group was injected by cis‐platinum 2 mg/kg ,once every 2 days ,a total of 14 days .The tumor volume was measured once per 3 d .After experiment ,the tumor weight was measured;the TUNEL staining was used to observe the morphological chan‐ges and cell apoptosis of tumor tissue in each group .The changes of Fas and FasL protein expression in tumor tissues were analyzed by immunohistochemistry .The FasL and IFN‐γlevels in peripheral blood were tested by the ELISA assay .Results ICA exerted no obvious inhibitory effect on the proliferation of Eca‐109 and TE‐13 cell in vitro .The average volume and weight of xenografts tumor had statistical difference between the experimental group and the positive control group (P<0 .05) .The TUNEL staining results showed that the tumor tissues had obvious apoptosis ,the number of apoptosis cells was significantly increased compared with the control group(P<0 .05) .The immunohistochemistry experimental results showed that the expression of Fas and FasL was signifi‐cantly increased(P<0 .05) .The ELISA experimental results demonstrated that the FasL and IFN‐γlevels of peripheral blood in the experimental group were significantly increased(P<0 .05) .Conclusion ICA had no obvious inhibitory effect on esophageal cancer cell proliferation in vitro ,but could induce in vivo apoptosis through the Fas expression and secretion of FasL and IFN‐γ,thus plays the role of anti‐esophageal cancer .
3.Construction of biotin-modified polymeric micelles for pancreatic cancer targeted photodynamic therapy.
Chun-yue DENG ; Ying-ying LONG ; Sha LIU ; Zhang-bao CHEN ; Chong LI
Acta Pharmaceutica Sinica 2015;50(8):1038-1044
In this study, we explored the feasibility of biotin-mediated modified polymeric micelles for pancreatic cancer targeted photodynamic therapy. Poly (ethylene glycol)-distearoyl phosphatidyl ethanolamine (mPEG2000-DSPE) served as the drug-loaded material, biotin-poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine (Biotin-PEG3400-DSPE) as the functional material and the polymeric micelles were prepared by a thin-film hydration method. The targeting capability of micelles was investigated by cell uptake assay in vitro and fluorescence imaging in vivo and the amounts of Biotin-PEG-DSPE were optimized accordingly. Hypocrellin B (HB), a novel photosensitizer was then encapsulated in biotinylated polymeric micelles and the anti-tumor efficacy was evaluated systemically in vitro and in vivo. The results showed that micelles with 5 mol % Biotin-PEG-DSPE demonstrated the best targeting capability than those with 20 mol % or 0.5 mol % of corresponding materials. This formulation has a small particle size [mean diameter of (36.74 ± 2.16) nm] with a homogeneous distribution and high encapsulation efficiency (80.06 ± 0.19) %. The following pharmacodynamics assays showed that the biotinylated micelles significantly enhanced the cytotoxicity of HB against tumor cells in vitro and inhibited tumor growth in vivo, suggesting a promising potential of this formulation for treatment of pancreatic cancer, especially those poorly permeable, or insensitive to radiotherapy and chemotherapy.
Animals
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Antineoplastic Agents
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chemistry
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Biotin
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Drug Carriers
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chemistry
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Drug Screening Assays, Antitumor
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Humans
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Micelles
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Pancreatic Neoplasms
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drug therapy
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Photochemotherapy
4.Effect of temperature sensitive umbilical cord mesenchymal stem cell therapy combined with mild hypothermia on cognitive function in rats of severe traumatic brain injury
Xiaohong LI ; Chong CHEN ; Yue TU ; Jingjing WANG ; Sai ZHANG ; Hongtao SUN
Chinese Journal of Trauma 2014;30(5):455-459
Objective To investigate the effect of temperature sensitive umbilical cord mesenchymal stem cells (tsUCMSCs) transplantation under mild hypothermia environment on cognitive function of rats after severe traumatic brain injury (TBI).Methods Thirty-six male SD rats weighing (300 ± 20)g were subjected to severe TBI by fluid percussion device (2.5 atm) and managed with tsUCMSCs combined with mild hypothermia.Rats were divided into three groups:sham operation group,TBI group,and TBI + tsUCMSCs + mild hypothermia group (TBI + intervention group) according the random number table,with 12 rats per group.Latency to the platform and the time in targeted quadrant were recorded to evaluate the learning and memory with Morris water maze.Population spike (PS) and excitatory postsynaptic potential (EPSP) of long-term potential (LTP) were examined to evaluate synaptic plasticity of hippocampus.Phosphorylated Tau at Thr231 and phosphorylated GSK3 at Ser9 were detected by Western blot.Results Latency to the platform [(15.9 ±3.2) s vs (8.08 ±2.69) s,P<0.01]was prolonged and time in targeted quadrant [(14.4 ± 3.0) s vs (36.3 ± 5.7) s,P < 0.01] was shortened in TBI group at day 28 compared with sham operation group.Whereas,latency to the platform [(10.7 ± 2.8) s,at Ser9 were detected by Western blot.Results Latency to the platform [(15.9 ± 3.2) s vs (8.08 ± 2.69) s,P < 0.01] was prolonged and time in targeted quadrant [(14.4 ± 3.0) svs (36.3 ± 5.7) s,P <0.01] was shortened in TBI group at day 28 compared with sham operation group.Whereas,latency to the platform [(10.7 ± 2.8) s,P < 0.01] and time in targeted quadrant [(29.4 ± 4.4) s,P < 0.05 |were reversed in TBI + intervention group.PS and EPSP of LTP were elevated in TBI group,but the elevation was suppressed in TBI + intervention group.Meanwhile,Tau hyperphosphorylation (0.80 ± 1.00vs 1.24 ±0.13,P<0.05) and GSK3 deactivation (3.01 ±0.41 vs 1.27 ±0.22,P <0.01) were significantly reversed in TBI + intervention group compared with TBI group.Conclusion Combination of tsUCMSCs and mild hypothermia therapy can improve the TBI-induced cognitive deficit.
5.Effect and mechanism of mild hypothermia in increasing proliferation and differentiation of endogenous neural stem cells after traumatic brain injury
Xiaohong LI ; Chong CHEN ; Xia ZHAO ; Haiqian LIANG ; Mingliang ZHAO ; Sai ZHANG ; Yue TU
Chinese Journal of Trauma 2014;30(6):500-503
Objective To investigate the effect of mild hypothermia on proliferation and differentiation of neural stem cells (NGCs) in hippocampal subgranular zone after traumatic brain injury (TBI) and the underlying mechanism.Methods SD rats were divided into sham-injured group (only left dura mater exposed),hypothermia group (sham injury + mild hypothermia therapy for 72 hours),TBI group (unilateral fluid percussion was used to generate severe TBI),and TBI + hypothermia group (TBI + mild hypothermia therapy for 72 hours) according to the random number table,with 8 rats per group.Hippocampal homogenates or brain tissues were harvested after BrdU (100 mg/kg) was intraperitoneally administered to rats once a day for 7 days postTBI.Expressions of BrdU and double cortin in hippocampal subgranular zone were respectively detected by immunohistochemical or immunofiuorescence staining.Level of Sirt1 (silence information regulatory proteins,Sirt1) in hippocampus was detected by Western blot.Results BrdU-and double cortin-positive cells in rat hippocampal subgranular zone greatly increased at 7 days after TBI in comparison with sham-injured group (P < 0.01).Moreover,BrdU and double cortin in rat hippocampal subgranular zone in TBI + hypothermia group was significantly higherthan that in TBI group [(257.4 ± 34.3) vs (196.4 ± 23.8) ; (346.4 ± 42.2) vs (245.7 ± 33.2),P <0.01].Moreover,mild hypothermia reversed TBI-induced over-expression of Sirt1 [(0.62 ± 0.075) vs(1.18 ± 0.11),P < 0.01].Conclusion Mild hypothermia therapy can promote proliferation andneuronal differentiation of NSCs in hippocampal subgranular zone after TBI and the possible mechanismmay relate to the inhibition of over-expression of Sia1.
6.Silence regulatory protein 1 promotes axonal outgrowth in vitro
Haiqian LIANG ; Xiaohong LI ; Jingjing WANG ; Yue TU ; Chong CHEN ; Sai ZHANG
Chinese Journal of Nervous and Mental Diseases 2014;(6):321-324
Objective To investigate the effect of silence regulatory protein 1 (Sirt1) on axonal outgrowth. Methods The hippocampal neurons was first isolated in vitro from rat embryos. The distribution and expression of Sirt1 were then detected 72 h later. The down-regulation of Sirt1 was induced by RNAi technology and up-regulation of Sirt1 was in-duced by overexpression of Sirt1 and resveratrol (RES). Immunofluorescence staining was used to examine the axon length. Results Immunofluorescence staining showed that Sirt 1 was located in neuronal cell body and neurite, especially in the distal axons. Down-regulation of Sirt1 significantly decreased axonal length compared with siRNA control group [(178.3 ± 3.2) μm vs. (110.2 ± 18.30) μm, P< 0.01 ]; Overexpression of Sirt1 significantly increased axonal length com-pared with eGFP control group [(178.3±3.2)μm vs (310.6±39.5)μm, P<0.01 ];Activation of Sirt1 by RES treatment al-so significantly increased axonal length compared with vehicle control group (DMSO treated group) [(291.7±13.2)μm vs. (525.1±49.1)μm, P<0.01 ]. Conclusions Sirt1 plays a key role in axonal growth which may be used as a potential thera-peutic target of axon regeneration.
7.Dynamic changes of brain cavity in rats after traumatic brain injury detected by MRI-based three-dimensional reconstruction
Feng FU ; Mingliang ZHAO ; Xiaohong LI ; Chong CHEN ; Lina WANG ; Hongtao SUN ; Yue TU ; Sai ZHANG
Chinese Journal of Tissue Engineering Research 2016;20(40):5946-5952
BACKGROUND:Currently, morphological observations of brain cavity after traumatic brain injury (TBI) via cadavers or animal specimen are difficult to obtain dynamic changes.
OBJECTIVE:To explore the application effect of MRI-based three-dimensional (3D) reconstruction for evaluating the prognosis of TBI.
METHODS:Five male Sprague-Dawley rats were enrol ed to establish TBI models by Electronic Cortical Contusion Injury (eCCI), and scanned by 3.0T MRI with Rat-coil to obtain the DICOM date of brain at 1 day, 1, 2 and 3 months after modeling. Brain cavities were 3-dimensional y reconstructed by Mimics16.0 software, and analyzed in the Meshmixer software.
RESULTS AND CONCLUSION:(1) The outline of reconstruction model image was clear, and could be observed and measured from different sides and perspectives. (2) The cavity volume and surface area at different time points after TBI showed significant differences between each other except that at 2 and 3 months (P<0.05). (3) The results of cavity change suggested that the cavity tended to be regular after 3 months of TBI. (4) In conclusion, 3D reconstruction software Mimics combining with model analysis software Meshmixer can conveniently and quickly obtain the cavity model, and provide an intuitive way for evaluating the dynamic variations of the brain cavity after TBI.
8.The influence of overexpression of NeuroD1 on transdifferentiation of spinal cord reactive astrocytes into neurons
Wenbo KANG ; Chong CHEN ; Xiaohong LI ; Jingjing WANG ; Yue TU ; Sai ZHANG ; Haiqian LIANG
Chinese Journal of Nervous and Mental Diseases 2015;(9):564-568
Objective To investigate the effect of the overexpression of NeuroD1 on mediating transdifferentiation of spinal reactive astrocytes into neurons. Methods Spinal cord astrocytes were cultured from the SD rat, and reactive astrocytes were prepared by scratches treatment. Cells were divided into blank groups (NV group), control virus group (GFP group) and NeuroD1 virus group (NeuroD1 group). At 7 d after scratches treatment, GFP and NeuroD1 groups were infected with retroviruses carrying the GFP gene and and GFP gene plus NeuroD1 gene, respectively,whereas NV group was not infected with the virus. Twenty-four hours late, the culture medium were replaced by neuron conditioned medi?um. Cell morphology was examined at 1, 2, 3, 5, 7 and 14 d. DCX positive and NeuN positive cells were detected at 7 d and 14 d after infection by using immunofluorescence staining method, respectively. Results After replacement with the neuron conditioned medium, the nucleus was obviously plump, the cytoplasm was thin and neurites was reduced and ex?tended. Compared with the NeuroD1 group, neurites of NV group and GFP group were shorter with many branches and the nucleus was smaller. At 7 d after infection, cell morphology of NV group and GFP group gradually recovered, but cell morphology of NeuroD1 group did not. Compared with NV group and GFP group, NeuroD1 group had more DCX(9.84 ± 2.06%)and NeuN(8.25±2.78%)positive cells [F values 40.107 for DCX and 21.73 for NeuN (P<0.05)]. Conclusion The overexpression of NeuroD1 can mediate the transdifferentiation of spinal reactive astrocytes into neurons.
9.Application research and design strategy on smart responsive mesoporous silica anti-tumor nanodelivery systems
Biao LI ; Ying-chong CHEN ; Bao-de SHEN ; Wen-ting WU ; Qin ZHENG ; Peng-fei YUE
Acta Pharmaceutica Sinica 2023;58(3):494-505
Malignant tumors are major diseases that endanger human health. Due to their complex and variable microenvironment, most anti-tumor drugs cannot precisely reach the focal tissue and be released in a controlled manner. Intelligent responsive nano carriers have become a hot spot in the field of anti-tumor drug delivery systems. As an excellent nano material, mesoporous silica has the advantages of non-toxic, stable, adjustable pore volume and pore diameter, and easy functional modification on the surface. By virtue of its perceptive response to the tumor microenvironment or physiological changes, it can achieve the targeted drug release or controlled drug release of the drug delivery system in the tissue, making it an ideal carrier for intelligent response drug delivery system. In this paper, we review the design strategies and current research status of smart responsive anti-tumor drug delivery systems based on mesoporous silica, in order to provide a reference for the development of anti-tumor drug nanoformulations.
10.Locking compression plate (LCP) combined with minimally invasive percutaneous plate osteosynthesis (MIPPO) for the treatment of Pilon fracture.
Qin LI ; Wen-bo ZHAO ; Chong-qi TU ; Tian-fu YANG ; Yue FANG ; Hui ZHANG ; Lei LIU
China Journal of Orthopaedics and Traumatology 2014;27(12):1029-1032
OBJECTIVETo summarize clinical outcomes of locking compression plate (LCP) combined with minimally invasive percutaneous plate osteosynthesis (MIPPO) for the treatment of Pilon fracture.
METHODSFrom January 2009 to December 2012, Pilon fracture patients treated by LCP with MIPPO were retrospectively analyzed. All open fractures, pathologic fractures and those who had limb vascular disease or nerve injury were excluded. Thirty-eight patients were enrolled, including 29 males and 9 females aged from 21 to 78 years old with an average of 48 years old. According to AO classification, 20 cases were type B, 18 cases were type C. Operative time, blood loss, reduction quality, time of fracture healing complications and postoperative ankle joint function were applied for evaluating clinical outcomes, AOFAS scoring were used for assessing postoperative clinical effects.
RESULTSAll patients were followed up from 13 to 24 months (averaged 18 months). All patients obtained bone union without any plate failures or loss of fixation/reduction. One patient occurred superficial wound infection, and resolved with antibiotics and local wound care. Postoperative average AOFAS score was 81 (ranged 65 to 97).
CONCLUSIONLCP with MIPPO for Pilon fratcure has advantages of less invasion, fewer complications and satisfactory ankle function.
Adult ; Aged ; Bone Plates ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; methods ; Retrospective Studies ; Tibial Fractures ; surgery