Gingival mesenchymal stem cells inhibited senescence of type Ⅱ alveolar epithelial cells and prevented radiation-induced pulmonary fibrosis / 中华放射医学与防护杂志

Objective:To investigate whether transplantation of gingival mesenchymal stem cells (GMSCs) can inhibit radiation-induced senescence of alveolar epithelial cells type Ⅱ (AECⅡ) and its role in the prevention of radiation-induced pulmonary fibrosis (RIPF).Methods:Mouse type Ⅱ alveolar epithelial cells (MLE12) were irradiated with 6 Gy X-rays and then co-cultured with GMSCs. The extent of cellular senescence of MLE12 cells was assessed by cell morphology, β-Gal staining, and senescence secretion-associated phenotype (SASP) assay. RIPF model was constructed by unilaterally irradiating the right chest of C57BL/6 mice with 17 Gy X-rays. GMSCs were transplanted 1 d after irradiation. At 180 d after irradiation, the pulmonary organ ratio, HE staining, and Masson staining were used to assess intra-pulmonary structure and interstitial collagen deposition in the lung. β-Gal immunohistochemistry and immunofluorescence co-localization with AECⅡ were measured to assess the degree of cellular senescence in the lung. The SASP expression changes in lung tissue were detected by qRT-PCR. The protein expressions in P53-P21 and P16 pathways were detected by Western blot assay. P21 expression in AECⅡ was detected by immunofluorescence co-localization assay.Results:GMSCs effectively inhibited radiation-induced senescence of MLE12 cells, reduced the ratio of radiation-elevated β-Gal positive cells by 11.8% ( t=6.72, P<0.05), and decreased the expressions of SASP (IL-6, IL-8, IL-1β) ( t=28.43, 28.43, 4.82, P<0.05). GMSCs transplantation improved the survival rate of irradiated mice, prevented radiation-induced alveolar structural collapse thickening and collagen deposition, reduced the number of senescent cells in the irradiated lung tissues by 23.9% ( t=21.83, P<0.05), and inhibited the expressions of SASP ( t=8.86, 20.63, P<0.05). GMSCs also inhibited the expression of P53-P21, P16-related proteins in MLE12 cells and lung tissues of mice after irradiation. Conclusions:GMSCs inhibit senescence-related P53-P21 and P16 pathways, prevent radiation-induced AECⅡ senescence, as well as the development of RIPF.

Role of umbilical cord mesenchymal stem cell transplantation in alleviating alveolar cell senescence / 中国辐射卫生

Objective@#To investigate whether the transplantation of umbilical cord mesenchymal stem cells (UC-MSCs) can alleviate radiation-induced pulmonary fibrosis (RIPF) and attenuate intrapulmonary cellular senescence in mice with RIPF.@*Methods@#The C57BL/6 mice were unilaterally irradiated with 17 Gy in the right lung to construct RIPF models. UC- MSCs were injected into the caudal vein at 3 months after radiation, and samples were taken at 6 months. The survival rate of mice was recorded, and the lung organ ratio was calculated. Lung structure and collagen deposition were observed by hem- atoxylin-eosin  staining  and  Masson  staining.  The  expression  of  senescence  secretion-associated  phenotype  (SASP)  was measured by quantitative real-time polymerase chain reaction. Intrapulmonary cellular senescence was assessed by β-Gal im- munohistochemistry. The expression of key proteins in the P53-P21 and P16 pathways was measured by Western blot. P21 expression in the lung was measured by tissue immunofluorescence.@*Results@#Compared with the untreated group, RIPF mice treated with UC-MSCs showed an improved survivalrate, reduced collagen deposition, and an improvement incollapse and thickening of alveolar structure. Increased β-Gal-positive senescent cells and high expression of SASP (IL-6, IL-8, IL- 1β) in the lung of RIPF mice were all reduced after UC-MSC treatment. The abnormally increased levels of P53, p-P53, P21 and P16 proteins in RIPF mice were reduced by UC-MSC treatment.@*Conclusion@#UC-MSCs may reduce cellular senes- cence in fibrotic lungs and alleviate RIPF by inhibiting P53-P21 and P16 pathways, which is expected to be used for the treatment of radiation-induced lung injury.

Progress in the treatment of radiation-induced pulmonary fibrosis with mesenchymal stem cells / 中华放射医学与防护杂志

Radiation-induced pulmonary fibrosis (RIPF) is a common complication of thoracic tumor radiotherapy. The main manifestation of radiation-induced pulmonary fibrosis is chronic progressive consolidation of pulmonary interstitium, which may cause the lung physiology function reduced or even lost. Furthermore, it can be lethal forrespiratory failure in severe cases. Recent studies have found that mesenchymal stem cells (MSC) play an important role in the modulation of proliferation and the activation of immune cells in lung inflammation. In addition, MSC can also play a part in the treatment of RIPF by differentiating into functional cells and secreting cytokines. Therefore, MSC has a good application prospect in RIPF as a cell therapy method. This article reviews the molecular mechanisms, influencing factors and current status of MSC therapy in RIPF.

Biomechanical Characteristics and Sports Risk Analysis on Foot-Ankle Joints of Badminton Players at the Moment of Landing / 医用生物力学

Objective To explore the influence of biomechanical characteristics of badminton players on sports risk at the moment of foot and ankle landing, so as to provide references basis for avoiding the sports risk of high-frequency and high-intensity landing of ankle joint of beginners. Methods Using three-dimensional force measuring platform and motion capture system, the kinematic and dynamic data of 30 badminton beginners (experimental group) and 30 high-level athletes (control group) at the kick-off (1 step) moment during ankle landing were collected. Results The angles of metatarsal flexion and dorsiflexion in experimental group were significantly smaller than those in control group, and the angles of varus and internal rotation in experimental group were significantly larger than those in control group. The left-right forces in experimental group were significantly larger than those in control group, and there was no significant difference in anterior-posterior force and vertical force between experimental group and control group. The valgus and external rotation torque of experimental group were significantly higher than those of control group, and the internal rotation torque of control group was significantly higher than that of experimental group. Conclusions Compared with beginners, the ankle movement of professional athletes has good dynamic stability and flexibility, the cushioning task can be completed with a smaller range of movement and force in left-right direction, and the angle of metatarsal flexion and dorsiflexion of professional athletes is relatively increased. It is also the embodiment of good training effect, so that the buffer time is slightly longer to prevent the impact of sudden landing of the ankle.

Functional mechanism of SIRT1 gene in tumor / 国际肿瘤学杂志

Sirtuin 1 (SIRT1),the Ⅲ class deacetylation enzyme,is a kind of NAD + dependent histone deacetylation enzyme.The role of SIRT1 in tumor has the duality.It can inhibit inflammation,tumor angiogenesis and interact with tumor related gene to inhibit tumor development.However,it can also regulate tumor related genes,and epithelial-mesenchymal transition,promote tumor cell proliferation and tolerance of radiotherapy and chemotherapy,and maintain the stemness of cancer stem cells to promote tumor proliferation,invasion and metastasis.

microRNA-140 suppresses the migration and invasion of colorectal cancer cells through targeting Smad3 / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effect of microRNA-140 (miR-140) on the migration and invasion of colorectal cancer (CRC) cells and the possible mechanism.</p><p><b>METHODS</b>miR-140 mimics, miR-140 specific inhibitor or small interfering RNA (siRNA) against Smad3 were transfected into human CRC cell line RKO cells respectively, using Oligofectamine or Lipofectamine2000. Quantitative real-time PCR (real-time PCR) was used to measure the expression levels of miR-140 and Smad3 mRNA. Smad3 protein was analyzed by Western blot. The in vitro cell migrating and invasive abilities were determined by wound-healing and Transwell chamber assay after up-regulating or down-regulating miR-140 or knocking down Smad3.</p><p><b>RESULTS</b>The Western blot assays showed that the Smad3 protein level was significantly reduced after up-regulating miR-140 (0.04 ± 0.01), compared with that of (0.47 ± 0.02, P < 0.05) in the control group and that of (0.52 ± 0.06) in the negative control group (P < 0.05 for both). The results of real-time PCR indicated that no significant difference was found in the levels of Smad3 mRNA between miR-140 transfection and NC groups (1.11 ± 0.13 vs. 1.00 ± 0.06, P > 0.05). The wound-healing assay showed that the migrating ability was dramatically attenuated by miR-140 compared with that in the control and NC groups, whereas no significance was found when compared with that of the Smad3 siRNA transfected cells. The number of cells migrating through Transwell chamber without matrigel in the miR-140 group was (76.2 ± 4.4), remarkably lowered than that in the control (267.1 ± 4.9) and NC (336.1 ± 5.7) groups (P < 0.05 for both), but no significant difference between the miR-140 (76.2 ± 4.4) and Smad3 siRNA (83.5 ± 7.3) groups. Transwell chamber with matrigel assay showed that number of cells penetrating through the membrane was (109.5 ± 7.4) in the miR-140 group, significantly lower than that in the control (403.1 ± 5.1) and NC (392.6 ± 8.4) groups (P < 0.05 for both), while Smad3 siRNA transfection had a similar effect (138.8 ± 3.6)(P > 0.05). Down-regulation of miR-140 increased the level of smad3 protein expression, and partially reversed the inhibition of the cell migration and invasion mediated by miR-140. Co-transfection of miR-140 inhibitor and Smad3 siRNA had no significant effect on the Smad3 protein expression and the abilities of cell migration and invasion.</p><p><b>CONCLUSIONS</b>miR-140 regulates the Smad3 expression at the post-transcriptional level. miR-140 suppresses the migrating and invasive abilities of CRC cells, possibly through down-regulation of Smad3. The findings of this study suggest that miR-140 may have a unique potential as a possible biomarker candidate for diagnosis and therapy of tumor metastasis.</p>