1.The role and mechanisms ofω-3 polyunsaturated fatty acids in inducing cell apoptosis and anti-prolif-eration in multiple myeloma
Yu ZHAO ; Xiaoting ZHU ; Yinan WANG
Practical Oncology Journal 2016;30(6):516-522
Objective To explore the role and mechanisms of ω-3 polyunsaturated fatty acids (ω-3PUFA) alone or in combination with dexamethasone ( DEX) in inducing cell apoptosis and anti -proliferation in multiple myeloma(MM).Methods DEX resistance MM cell line MM1R were treated with different concentra-tions of Eicosapentaenoic acid(EPA)or Docosahexaenoic acid(DHA)alone or in combination with DEX for 24hrs or 48hrs.Cell proliferation was detected by MTT .Cell cycle and apoptosis were measured by flow cytometry .The levels of apoptosis related proteins were analyzed by Western blot .Results The proliferation of MM1R was in-hibited by different concentrations (10,20,50,100μM)of EPA or DHA alone or in combination with 10μM DEX in a dose-and time-dependent manner .Inhibition effect was significantly higher in combinative groups than in single agent groups(P<0.05).The percentage of G0/G1 phase and cell apoptosis rate in MM1R treated with dif-ferent concentrations of EPA or DHA alone was increased in a dose -dependent manner ,and being significantly higher in combinative groups than in single agent groups (P<0.05).The expressive levels of cleaved caspase -3 and Bax were up-regulated ,while pro-caspase-3 and BCL-2 were down-regulated in a dose-dependent manner.Conclusion ω-3PUFA can inhibit DEX resistant MM cell proliferation ,arrest cell cycle and induce cell apoptosis ,and has a synergistic anti -resistant effect in combination with DEX ,may serve as a new ,effective MM drugs.
2.Construction and evaluation of a novel dendrimer vector-DNA vaccine for schistosomiasis japonica
Xiaoting WANG ; Yinchang ZHU ; Qiuduan GAO ; Lingxiang GUO ; Xinsong LI
Chinese Journal of Schistosomiasis Control 2010;22(1):5-12
Objective To construct and evaluate a novel PAMAM dendrimer vector-DNA vaccine for schistosomiasis japonica.Methods Lysine was used to modify 4.0G PAMAM.and the modified product PAMAM-Lys was synthesized.Agarose gel electrophoresis was used to confirm the composite ratio of plasmid DNA and dendrimer.Micrestructure of the compound was observed by using transmission electronic microscopy,and the stability was analyzed by using electrophoresis.The viability of the cells transfected with dendrimers was evaluated by using a MTT technique in vitro.Fiftyty mice were immunized with purified plasmid pJW4303,pJW4303-Sj23 dendrimer PAMAM-Lys and compound PAMAM-Lys/pJW4303-Sj23,respectively.The specific antibodies of the mice in each group were detected to access the immunoreactivity.Results The agarese gel electrophoresis showed that when the charge ratio of the dendrimer vector and DNA was between 2 and 4,the positive and negative charges could be counteraeted completely,and the compound was blocked completely by DNA electrophoresis.The obscrvation results with transmission electronic microscopy showed that the composition of dendrimer vector and DNA caused shrink of DNA structure.Dendrimer-DNA compound had a good stability.MTT showed the modified dendrimer vector and DNA compound system produced a lower cell toxicity on 293T cell than the unmodified Ones.Thk levels of specific antibodies of the mice immunized with PAMAM-Lys/pJW4303Sj23 were significantly higher than those of the mice immunized with naked DNA vaccine(P<0.05).Conclusions The lysinemodified PAMAM-lys is an excellent vector,and has an appropriate biocompatibility.Lysine-modification can reduce the cell toxicity of PAMAM dendrimer significantly.PAMAM-Lys can enhance the immunoreactivity of DNA vacmine which merits further application in schistosomiasis DNA vaccine.
3.The role of spinal cord p300 in chronic constriction nerve injury-induced neuropathic pain in rats
Xiaoting TANG ; Xiaoyan ZHU ; Changsheng HUANG ; Qulian GUO
Journal of Chinese Physician 2014;16(12):1602-1605
Objective To explore the role of spinal cord p300 in neuropathic pain induced by chronic constriction nerve injury (CCI) in rats.Methods Thirty two Sprague-Dawley (SD) rats were randomly divided into sham and CCI groups,14 days after surgery,immuno-fluorescence staining and Western blot were used to detect distribution and expression of p300 protein.After rats were successfully implanted with an intrathecal catheter and accepted CCI surgery,another 24 rats were randomly divided into three groups (n =8):dimethyl sulfoxide (DMSO) group,p300 acetyltransferase inhibitor C646 group,and control C37 group.Each rat were administered through the intrathecal catheter from day 7 to 14 and mechanical withdraw threshold were tested.Results (1) The p300 positive cells were detected mainly in neurons,and p300 protein in spinal cord of CCI group were significantly higher than sham group (P <0.05).(2) C646 alleviated significantly neuropathic pain in rats,without significant changes in pain threshold after injection of C37 and DMSO.Conclusions The p300 protein in spinal cord was involved in the development of neuropathic pain in rats,the mechanism may be referred to its acetyltransferase activity.
4.Correlation Between Intravoxel Incoherent Motion and Prognostic Factors of Rectal Cancer
Haibin ZHU ; Xiaoting LI ; Shuai WANG ; Yingshi SUN
Chinese Journal of Medical Imaging 2017;25(3):211-215
Purpose To explore the correlation between quantitative parameters from intravoxel incoherent motion (IVIM) with prognostic factors of rectal adenocarcinoma.Materials and Methods Eighty-six patients with rectal adenocarcinoma who were underwent surgery without neoadjuvant therapy in our hospital between September 2015 and July 2016 were selected in this retrospective study.The image data included multiple b-values diffusion weighted imaging (DWI) examination and the corresponding D,D* and f values of the lesions.Relationships between the quantitative parameters and tumor pathology indexes including histological differentiation grade,tumor T/N stage,lymphangiovascular invasion state,the expression level of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (Her-2) were assessed.Results The average D values of different differentiation degree (high,middle and low) of rectal adenocarcinoma were (0.541±0.093)×10 3mm2/s,(0.490±0.156)×10-3mm2/s and (0.342 ± 0.147)× 10-3 mm2/s,and the difference was statistically significant (P<0.05).TheD values were significantly different between the lymphangiovascular invasion and non invasion state [(0.511 ±0.154)× 10-3 mm2/s vs (0.387±0.130)×10-3 mm2/s,P<0.05)].However,there were no significant differences in the mean D,D* and f values among different tumor T/N stage (P>0.05).The average f value of EGFR or Her-2 high expression group was higher than that of low expression group (0.379±0.076 vs 0.298±0.099,P<0.01;0.356±0.097 vs 0.298±0.098,P<0.05,respectively).Conclusion Quantitative parameters of IVIM in rectal adenocarci-noma can be used as noninvasive imaging biomarkers to predict the biologic behavior of tumor and the prognosis of the patients.
5.A case report of left middle posterior insula infarction
Xiaoting LIU ; Youling ZHU ; Min TANG ; Chunhua XI
Chinese Journal of Geriatrics 2017;36(8):936-937
6.Effects of quercitrin on the proliferation and the cytotoxicity of human γδT cells
Lu ZHENG ; Yongqiang CHEN ; Junquan LIU ; Zhonghai ZHOU ; Yang YANG ; Xiaoting LYU ; Yun ZHU ; Fuxing CHEN
Chinese Journal of Microbiology and Immunology 2014;(6):437-441
Objective To investigate the in vitro effects of quercitrin on the proliferation and the cytotoxicity of human γδT cells.Methods Peripheral blood mononuclear cells (PBMCs) were isolated from healthy subjects and cultured with isopentenyl pyrophosphate and IL -2 to induce human γδT cells.The hu-manγδT cells were cultured with quercitrin at various concentrations for 48 hours.CCK-8 kits were used to analyze the in vitro proliferation and cytotoxic activities of γδT cells.Flow cytometry was performed to meas-ure the expression of granzyme B and perforin in γδT cells.The expression of p-ERK, p-Akt and Bcl-2 at protein level were detected by Western blot .Results The percentage of human γδT cells in PBMCs was in-creased from (2.96±1.83)%to (88.94±2.36)%after 10 days of culture.The quercitrin at concentrations of 10 to 80 μg/ml could promote the growth of γδT cells and up-regulate the expression of granzyme B , per-forin, p-ERK, p-Akt and Bcl-2 in a dose dependent manner .The cytolytic activities of γδT cells against co-lonic carcinoma cells ( HCT116 ) were enhanced by quercitrin .Conclusion Quercitrin could promote the proliferation of γδT cells and enhance the expression of granzyme B and perforin at certain concentrations in vitro.ERK1/2 and Akt signal transduction systems might be involved in the process .
7.Application of copeptin and APACHE in assessment of acute paraquat poisoning
Jing LI ; Ye PENG ; Guoying MA ; Fantuo KONG ; Baoyue ZHU ; Xiaoting LIU ; Weizhan WANG
The Journal of Practical Medicine 2014;(13):2072-2074
Objective To study the value of copeptin and APACHE Ⅱ used for assessing acute paraquat poisoning (APP). Methods One hundred and twenty six APP patients were divided into survival group (n = 58) and death group (n = 68), with clinical death as the endpoint of observation. 3 mL blood was obtained from each subject at 2 h , 24 h and 7 d after admission for detecting the levels of copeptin , and APACHE Ⅱ scores were recorded at the same time. Results There was significant difference in dosages of paraquat taken in the death group and the survival group , but the differences were significant in the rescue time , the first time for hemoperfusion and the times for hemoperfusion. 2 h after admission , the death group and survival group had significant difference in elevated copeptin but no significant difference in scores by APACHE Ⅱ. 24 h after admission copeptin decreased to normal level in the survival group but maintained at a higher level in the death group, while the scores by APACHE Ⅱ had insignificant difference between two groups. 7 d after admission, copeptin kept at a higher level and the scores by APACHE Ⅱwere significantly increased in the death group , with significant differences compared to the survival group. The oral doses of pesticides the patients took were positively correlated with copeptin level and scores by APACHE Ⅱ. Conclusion Repeated detection of copeptin and APACHE Ⅱ score are of clinical importance for the assessment of prognosis of APP patients and reasonable distribution of medical resources.
8.Copeptin and ischemia modified albumin level changes and clinical significance of myocardial injury in patients with acute organophosphorus pesticide poisoning
Jing LI ; Xiaoting LIU ; Chunhui TIAN ; Fantuo KONG ; Baoyue ZHU ; Lan WANG ; Weizhan WANG
Chongqing Medicine 2014;(31):4190-4192
Objective To investigate the clinical value of copeptin and ischemia modified albumin combined determination in the early diagnosis and clinical significance in myocardial damage of acute organic phosphorus pesticide poisoning .Methods Eighty‐six cases of AOPP patients were divided into two groups :the myocardial injury group (50 cases) and non myocardial injury group (36 cases) ;30 healthy people were selected as the control group .3 mL of venous blood were collected for all subjects involved within one hour in admission ,and their cTnI ,IMA and copeptin levels were detected .Results Compared with the control group ,the copep‐tin levels of non myocardial injury group and myocardial injury group were elevated and there was significant difference (P< 0 .05) ;the difference between myocardial injury group and non myocardial injury groups was also significantly different (P< 0 .05) .Among them ,the comparison between severe and mild to moderate group revealed that the IMA and copeptin levels reduced obviously ,there was significant difference (P< 0 .05) ;in myocardial injury group ,the IMA and copeptin levels of patients in different poisoning de‐gree were negatively correlated .Conclusion Early determination of IMA and copeptin level has important significance in the early diagnosis of myocardial injury in patients with poisoning in AOPP ,and could provide guidance for clinical medication .
9.Effect of continuous aspiration of subglotlic secretions on the prevention of ventilator-associated pneumonia in mechanically ventilated patients:a prospective, randomized, controlled clinical trial
Gongshan YANG ; Haibo QIU ; Yunping ZHU ; Yingzi HUANG ; Xiaoting XU ; Liang GAO
Chinese Journal of Internal Medicine 2008;47(8):625-629
Objective To evaluate the effect of continuous aspiration of subglottic secretions (CASS) on the prevention of ventilator-associated pneumonia (VAP) in mechanically ventilated patients. Methods Patients ventilated mechanically at the ICU from October, 2004 to April,2006 were randomly divided into 2 groups: one group received CASS and the other did not (NASS group). CASS was performed immediately after admission for patients in the CASS group. The diagnosis d VAP was made based on clinical presentations, and the evaluation of YAP was done using simplified version of the clinical pulmonary infection score (CPIS). The general status of the patients, days of ventilated treatment, the volume of daily aspirated aubglottic secretions, the morbidity and timing of VAP, days of stay in ICU and mortality within 28 days of hospitalization were recorded. Results One hundred and one patients were included in the study. There were 48 patients in the CASS group who were treated with mechanical ventilation more than 48 hours,and 43 patients in the NASS group. There was no significant difference in the general status of the patients and days of ventilation between 2 groups with the averaged score of APACHE Ⅱ being 20.8± 6.1. The average of CPIS was of 5.6±1.0 when VAP was diagnosed. The mean volume of aspirated subglottic secretions within the first 24 hours in the CASS group (n=48) was (27.2±21.2)ml. The morbidity of VAP in the CASS and the NASS groups was 25.0% and 46. 5% respectively (P=0.032), and the length of time before the onset of VAP in these 2 groups was (7.3±4.2) days and (5.1±3.0) days respectively (P=0.100). There was a significant increase in the percentage of gram-positive cocci from the lower respiratory tracts in the NASS group compared with that in the CASS group (P=0.004). In the CASS group, the volume of the first daily aspirated subglottic secretions in patients with VAP was significantly less than that in patients without VAP(P =0.006). The morbidity of VAP in patients with failed early aspiration (the volume of first daily aspirated secretions≤20 ml) was significantly higher than that in patients in whom the aspiration was effective (P<0.01). The length of mechanical ventilation in patients with VAP was significantly longer than that in patients without VAP(P=0.000). The in-hospital mortality in patients with VAP was significantly higher than that in patients without VAP(P=0.009), and the mortality in 28 days after admission in patients with VAP was significantly higher than that in patients without VAP(P=0.035).Conclusion Effective continuous aspiration of subglottic secretions could significantly reduce the morbidity of early-onset VAP.
10.Roles of UⅡ/UT system played in innate immune inflammatory signal pathway TLR4-IRF3 in LPS-stimulated primary Kupffer cells
Wenjuan TU ; Xiaoting WANG ; Liangming LIU ; Tong ZHU ; Dongyu LIANG ; Zhiwen YANG ; Deyong GAO
Chinese Journal of Immunology 2014;(10):1313-1319
Objecitve:To investigate effects of urotensin Ⅱ( UⅡ)/UT system on innate immune inflammatory signal pathway TLR4-IRF3 in the lipopolysaccharide (LPS)-stimulated Kupffer cells (KCs).Methods: Rat KCs were isolated and cultured.Pro-in-flammatory cytokines including IL-6,IFN-βand IFN-γwere assayed by ELISA in culture supernatant of KCs.Cell surface TLR4 were tested with flow cytometry technique.Expression of IRF3 were tested with real-time PCR and Western blot.Results: Significant increases were showed in IL-6, IFN-βand IFN-γsecretion, TLR4-expressed positive rates and IRF3 mRNA levels in KCs after stimulated by LPS,but were inhibited via urantide pretreatment.In addition,LPS induced upregulation of nuclear IRF3 protein and downregulation of cytoplasm IRF3 protein in KCs,which were blocked by urantide pretreatment.Conclusion:UⅡ/UT system mediates immune inflammatory response in part through activating TLR 4-IRF3 pathway in LPS-stimulated KCs.