BACKGROUND:Bone marrow mesenchymal stem cels have a therapeutic effect on acute lung injury, but the mechanism is unclear. If the mechanism is understood, the majority of patients with acute lung injury can obtain a benefit. OBJECTIVE:To explore the possible mechanism underlying bone marrow mesenchymal stem cels in the treatment of acute lung injury with sepsis in rats. METHODS: (1) Thirty-six adult Wistar rats were randomly divided into three groups, sham operation group (sham group), sepsis group and bone marrow mesenchymal stem cels group (cel treatment group). In the sepsis and cel treatment groups, animal models of sepsis with acute lung injury were established by cecal ligation and puncture, while in the sham group, the cecum was not ligated and punctured. Then, 1 mL normal saline was injected via the femoral vein in the sepsis and sham groups, and 1 mL bone marrow mesenchymal stem cel suspension (1×109/L) was injected into the cel treatment group. After 6 hours, interleukin 10 and macrophage inflammatory protein-2 levels in serum were measured in the three groups. Lung tissues were taken for pathological observation using hematoxylin-eosin staining. (2) Rat alveolar macrophages were obtained by bronchoalveolar lavage, seeded into 24-wel culture plates, and divided into three groups: control group (group A), sepsis model group (group B) and intervention group of bone marrow mesenchymal stem cels (group C). Normal saline, septic plasma, and co-intervention of septic plasma and mesenchymal stem cels were used in the groups A, B, C, respectively. Then, cels in the three groups were cultured in a 5% CO2 incubator at 37℃ for 1 hour. After that, alveolar macrophages were taken to detect whether nuclear factor-κB (P65) protein entered into the nucleus using laser scanning confocal microscopy. RESULTS AND CONCLUSION: (1) The results of animal experiments showed that compared with the sham group, the macrophage inflammatory protein-2 levels in the sepsis group and cel treatment group were significantly increased (P < 0.05), but the macrophage inflammatory protein-2 level in the cel treatment group was significantly lower than that in the sepsis group (P < 0.05); there were no significant differences in serum interleukin 10 levels among the three groups (P > 0.05); inflammatory cel infiltration, interstitial pulmonary edema and pulmonary hemorrhage existed in the sepsis and cel treatment groups, but these symptoms were significantly reduced in the cel treatment group compared with the sepsis group. (2) Results from cel experiments showed that compared with the group A, in group B and group C, the number of nuclear factor-κB (P65) proteins into the nucleus was significantly higher (P < 0.05), but it was lower in the group C than the group B (P < 0.05). These findings indicate that bone marrow mesenchymal stem cels in acute lung injury with sepsis can regulate nuclear factor-κB (P65) protein of alveolar macrophages into the nucleus, reduce expression of macrophage inflammatory protein-2, and thereby play a protective role in the lungvia reducing neutrophil infiltration. Temporarily, this study cannot explain whether bone marrow mesenchymal stem cels have an effect on interleukin 10.

OBJECTIVEIn order to investigate the potential mechanisms in troglitazone-induced apoptosis in HT29 cells, the effects of PPARγ and POX-induced ROS were explored.

METHODS[3- (4, 5)-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay, Annexin V and PI staining using FACS, plasmid transfection, ROS formation detected by DCFH staining, RNA interference, RT-PCR & RT-QPCR, and Western blotting analyses were employed to investigate the apoptotic effect of troglitazone and the potential role of PPARγ pathway and POX-induced ROS formation in HT29 cells.

RESULTSTroglitazone was found to inhibit the growth of HT29 cells by induction of apoptosis. During this process, mitochondria related pathways including ROS formation, POX expression and cytochrome c release increased, which were inhibited by pretreatment with GW9662, a specific antagonist of PPARγ. These results illustrated that POX upregulation and ROS formation in apoptosis induced by troglitazone was modulated in PPARγ-dependent pattern. Furthermore, the inhibition of ROS and apoptosis after POX siRNA used in troglitazone-treated HT29 cells indicated that POX be essential in the ROS formation and PPARγ-dependent apoptosis induced by troglitazone.

CONCLUSIONThe findings from this study showed that troglitazone-induced apoptosis was mediated by POX-induced ROS formation, at least partly, via PPARγ activation.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Chromans ; pharmacology ; Cytochromes c ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; HT29 Cells ; Humans ; PPAR gamma ; metabolism ; Proline Oxidase ; metabolism ; Reactive Oxygen Species ; metabolism ; Thiazolidinediones ; pharmacology

BACKGROUND: After general thoracic surgery, a chest tube is usually placed for closed drainage to expel gas accumulation in the thoracic cavity and fluid accumulation to promote lung re-expansion. It can also be observed whether there is active bleeding after the operation and whether there is a pulmonary leak. The conventional drainage of the chest cavity is connected with a water-sealed drainage bottle, and the patient condition is judged by observing the drainage situation and the fluctuation of the water column, which is a very classic method. However, the water-sealed bottle has the disadvantages of being easy to overturn and inconvenient to carry, which is not conducive to the early activities of patients. Under the concept of accelerated rehabilitation, our center applied a new type of anhydrous thorax negative pressure drainage device and achieved good results. The purpose of this study was to observe the effect of a new type of anhydrous thoracic negative pressure drainage device in patients after thoracic surgery. METHODS: Retrospective analysis of patients who underwent lung surgery in the First Affiliated Hospital of Zhejiang University Medical College from January 2018 to December 2019, patients were divided into two groups. One group of patients used a traditional closed-chest drainage water-sealed bottle as a control group, and the other group used a new type of anhydrous negative-pressure drainage bottle as an experimental group. Patients' gender, age, hypertension, diabetes, smoking history, surgical incisions and surgical methods, and the length of hospital stay and postoperative hospital stay were calculated. RESULTS: There were no statistical differences in age, gender, comorbidities (hypertension, diabetes, smoking history), scope of surgery, and duration of surgery between the two groups of patients, but there were statistical differences in surgical incisions between the two groups of patients (P=0.01). We found that patients using the new waterless negative pressure drainage device were shorter than patients with water negative pressure drainage device in terms of postoperative hospital stay and total hospitalization time, and the difference was statistically significant (P=0.02, P=0.04). CONCLUSIONS The new type of anhydrous thoracic negative pressure drainage device has a good effect on the rapid recovery and advancement after thoracic surgery.