Cell Division Cycle 2 Protects Neonatal Rats Against Hyperoxia-Induced Bronchopulmonary Dysplasia

Purpose@#Hyperoxia-induced bronchopulmonary dysplasia (BPD) is a lung disease in preterm infants. We aimed to explore the role of cell division cycle 2 (CDC2) on histopathologic changes of lung tissues, as well as the viability, apoptosis, and inflammation of lung cells in rats with hyperoxia-induced BPD. @*Materials and Methods@#Hyperoxia-induced BPD in neonatal rats and hyperoxia-induced A549 cells were constructed. The mRNA expression of CDC2 was detected by qRT-PCR. The fibrosis score of lung tissues was evaluated by hematoxylin-eosin staining. The viability and apoptosis of A549 cells were detected by cell counting kit-8 assay and flow cytometry. The protein expressions of bcl-2, bax, and caspase-3 were measured by western blot. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β in A549 cells were detected by enzyme-linked immunosorbent assay. The pcDNA3.1-CDC2 was injected into rats to determine the role of CDC2 in hyperoxia-induced BPD in vivo. @*Results@#The expression of CDC2 was decreased in lung tissues of neonatal rats with hyperoxia-induced BPD and hyperoxia-induced A549 cells. The fibrosis score was increased in the lung tissues of neonatal rats with hyperoxia-induced BPD. Overexpression of CDC2 increased the viability and protein expression of bcl-2; and inhibited the apoptosis, inflammation, and protein expression of bax and caspase-3 in hyperoxia-induced A549 cells. Up-regulation of CDC2 alleviated the histopathologic changes in lung tissues of neonatal rats with hyperoxia-induced BPD. @*Conclusion@#Overexpression of CDC2 promoted the viability and inhibited the apoptosis and inflammation of hyperoxia-induced cells, and alleviated the histopathologic changes of lung tissues in neonatal rats with hyperoxia-induced BPD.

Effects on the expression of lipopolysaccharide-induced inflammatory cytokines mediated by bovine bactericidal/permeability-increasing protein / 生物工程学报

Bactericidal/permeability-increasing protein (BPI) can bind to and specifically neutralize lipopolysaccharide (LPS) from the outer membrane of Gram-negative bacteria. In order to evaluate potent LPS-neutralizing activity of bovine BPI, the full-length coding sequence (1 449bp) or 714 bp N-terminal coding sequence (BPI714) of bovine BPI was transfected into mHEK293 cells and the expression of LPS-induced inflammatory cytokines was studied. First, we constructed the lentiviral expression vectors and generated mHEK293 cells stably expressing recombinant bovine BPI or BPI714. Then, we detected the expression of IL-8, IL-1β, TNF-α, NF-κB-1 and NF-κB-2 genes by real-time PCR at 0, 1, 3, 6, 12, 24, 36 and 48 h post of LPS induction in cells with or without recombinant bovine BPI or BPI714 ectopic expression, respectively. In response to LPS, the robust abundance of inflammatory cytokines including IL-8, IL-1β, TNF-α and NF-κB-2 was observed in wild type mHEK293 cells at eachtime point. On the contrary, mRNA abundance of IL-8, TNF-α and NF-κB-2 in transfected mHEK293 cells showed no significant changes at each indicated time point. Our results demonstrated that recombinant bovine full length BPI or BPI714 down-regulated the expression of inflammatory cytokines and revealed that either of bovine BPI or BPI714 was able to inhibit the immune respond stimulated by LPS. This study provides evidence for further investigating the mechanisms and application of BPI/LPS-neutralizing activity and also documents a reliable approach for analysis of the efficacy of antibacterial proteins.

Application of SWO technique in IMRT plan of post-operative cervical cancer / 中华放射医学与防护杂志

Objective To investigate the impact of segment weight optimization(SWO) technique on the intensity modulated radiation therapy(IMRT) plan for post-operative cervical cancer regarding the number of segments,monitor units (MU),the target homogeneity index (HI),conformal index (CI) and dose distribution of target volume and normal tissues.Methods Ten patients with stage Ⅰ and Ⅱ cervical cancer after radical resection were randomly selected for this study.The initial IMRT treatment plans were generated using ELEKTA XIO 4.62 system based on the step and shoot method (S-IMRT plan).With the same directions of fields and optimization parameters,the SWO tool was introduced to optimize the IMRT plans further (SWO-IMRT plan).Then the number of segments and MU were compared between the S-IMRT plan and SWO-IMRT plan.By using the dose-volume histogram (DVH),the target homogeneity index (HI),conformal index (CI) and dose distribution in the volumes of target and normal tissues were also analyzed.Results Compared with S-IMRT plan,the average number of segments in SWO-IMRT plan was decreased from 96 ± 4 to 87 ± 4 (t =10.049,P ＜ 0.05),and MU was increased from(638.79±35.02)) cGy to (672.03 ±39.07) cGy (t =3.5952,P ＜0.05).The maximum and mean doses of the planning target volume (PTV) decreased (t =2.262,2.323,P ＜ 0.05).A reduction of the maximum dose in the spinal cord was also observed [from (3856.00 ± 112.14) cGy to (3750.00 ± 141.38) cGy,t =3.976,P ＜ 0.05].The values of V30,V40,V50 in bladders,rectal V30 and L-femoral V50 were reduced in the SWO-IMRTplan (t=4.223,5.801,7.534,2.451,2.269,3.976,P ＜0.05).However,there was no significant difference in target homogeneity index(HI),conformal index (CI),rectal V40,V50,L-femoral V30,V40,V50,R-femoral V40 and V50.Conclusions The application of SWO technique in the IMRT planning for cervical post-operative cancer could reduce the total number of segments,doses in the spinal cord and bladder,but increase the total number of MU.As a result,the spinal cord and bladder toxicity can be reduced which enables an opportunity for dose escalation of gross tumor volume (GTV).SWO technique provides clinicians with an optional optimization solution in IMRT plan for post-operative cervical cancer patients.