Transforming growth factor-beta 1 (TGF-β1) plays important roles in the endothelial-to-mesenchymal transition (EndMT). Recently, long noncoding RNAs (lncRNAs) have been identified to be involved in the physiological and pathological processes of human diseases. However, the role of endothelial lncRNAs in the TGF-β1-mediated control of angiogenesis and its underlying mechanism remains largely unclear. In this study, we first demonstrated that TGF-β1 induced EndMT; promoted cell viability, proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Second, our study displayed that TGF-β1 upregulated the lncRNA UCA1 expression in HUVECs, knocked down UCA1 with small interfering RNAs, and inhibited the function of TGF-β1 in HUVECs. Third, our study showed that UCA1 was located in the cytoplasm and absorbed miR-455 in TGF-β1-treated HUVECs. Further, the miR-455 inhibitor restored the role of the inhibited UCA1 in HUVECs treated with TGF-β1. Fourth, our study revealed that miR-455 inhibited ZEB1 expression, and overexpression of ZEB1 restored the role of miR-455 in HUVECs treated with TGF-β1. Finally, our study revealed that UCA1 exerted its role via regulating the UCA1/miR-455/ZEB1 regulatory axis in HUVECs treated with TGF-β1. Collectively, our study identified the role of the UCA1/miR-455/ZEB1 pathway in HUVECs treated with TGF-β1 and indicated the potential therapeutic role of this regulatory axis in angiogenesis.
Polycystin-2 (PC2), which is a transmembrane protein encoded by the PKD2 gene, plays an important role in kidney disease, but its role in lipopolysaccharide (LPS)-induced acute lung injury (ALI) is unclear. We overexpressed PKD2 in lung epithelial cells in vitro and in vivo and examined the role of PKD2 in the inflammatory response induced by LPS in vitro and in vivo. Overexpression of PKD2 significantly decreased production of the inflammatory factors TNF-α, IL-1β, and IL-6 in LPS-treated lung epithelial cells. Moreover, pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, reversed the inhibitory effect of PKD2 overexpression on the secretion of inflammatory factors in LPS-treated lung epithelial cells. We further demonstrated that overexpression of PKD2 could inhibit LPS-induced downregulation of the LC3BII protein levels and upregulation of SQSTM1/P62 protein levels in lung epithelial cells. Moreover, we found that LPS-induced changes in the lung wet/dry (W/D) weight ratio and levels of the inflammatory cytokines TNF-α, IL-6 and IL-1β in the lung tissue were significantly decreased in mice whose alveolar epithelial cells overexpressed PKD2. However, the protective effects of PKD2 overexpression against LPS-induced ALI were reversed by 3-MA pretreatment. Our study suggests that overexpression of PKD2 in the epithelium may alleviate LPS-induced ALI by activating autophagy.
Objective To explore the advantage of warm liquid lavaging in laparoscopy surgery.Methods 60 cases of gynecologic patients ungerwent laparoscopy surgery were randomily divided into experimental group and control group,each consisting of 30 cases.38℃ natrii chloride using to wash abdominal cavity during operation in experimental group,while control group using room temperature natrii chloride.The incidence of shivering rate and change of body temperature were compared between two group.Results The body temperature in experimental group was higher than that in control group 30 mins during operation and operative accomplishment,but the incidence of shivering rate in experimental group was less than that in control group(P0.01).Conclusion Using warm liquid washing abdominal cavity during operation in laparoscopy surgery can reduce complications.
Abstract Transient global cerebral ischemia (tGCI) is a cerebrovascular disorder that can cause apoptotic neuronal damage and functional deficits. Basic fibroblast growth factor (bFGF) was reported to be highly expressed in the central nervous system (CNS) and to exert neuroprotective effects against different CNS diseases. However, the effects of bFGF on tGCI have not been studied intensively. This study was conducted to investigate the effect of bFGF and its underlying mechanism in an animal model of tGCI. After intracerebroventricular (i.c.v.) injection of bFGF, functional improvement was observed, and the number of viable neurons increased in the ischemia-vulnerable hippocampal CA1 region. Apoptosis was induced after tGCI and could be attenuated by bFGF treatment via inhibition of p53 mitochondrial translocation. In addition, autophagy was activated during this process, and bFGF could inhibit activation of autophagy through the mTOR pathway. Rapamycin, an activator of autophagy, was utilized to explore the relationship among bFGF, apoptosis, and autophagy. Apoptosis deteriorated after rapamycin treatment, which indicated that excessive autophagy could contribute to the apoptosis process. In conclusion, these results demonstrate that bFGF could exert neuroprotective effects in the hippocampal CA1 region by suppressing excessive autophagy via the mTOR pathway and inhibiting apoptosis by preventing p53 mitochondrial translocation. Furthermore, our results suggest that bFGF may be a promising therapeutic agent to for treating tGCI in response to major adverse events, including cardiac arrest, shock, extracorporeal circulation, traumatic hemorrhage, and asphyxiation.
Objective To investigate the regulatory effects of PTEN-PI3K/AKT pathway on the apoptosis of gastric cancer MKN28 cells and the possible mechanisms. Methods The specific sequence of PTEN was transfected to MKN28 cells by eukaryotic expression vector （transfection group）, and then vacant vector （negative control group） and PBS （blank control group） were transfected to the MKN28 cells, respectively. The effects of FFEN-PI3K/AKT pathway on the apoptosis of MKN28 cells and the expressions of PI3K, AKT, Caspase-3 and Caspase-9 were investigated. The growth curve and apoptosis of the MKN28 cells were detected by MTF assay and TUNEL staining, respectively, and the protein expression was detected by the Western blot. MKN28 cells which did not transfeeted by the PTEN were processed by inhibitor of PI3K （LY294002） （treated group）, and MKN28 cells in the control group were processed by PBS. The expressions of apoptosis protein and apoptosis-related protein were detected after inhibition of PI3K. All data were analyzed using the t test. Results The model of over-expression of PTEN was obtained and transfected into MKN28 cells. The survival of MKN28 cells in the transfection group was significantly inhibited in a time-dependant manner （ r = 0. 938, P 〈 0.05 ）. The mean apoptotic rate of the transfection rate was 27.86% ± 4.78% , which was significantly higher than 0.01% ± 0.01% of the negative control group （ t = 9. 527, P 〈 0.05）. The protein expression of PI3K in the transfection group was 0.25 ±0.03, which was significantly lower than 0.93 ± 0.16 of the blank control group and 0.96 ± 0. 15 of the negative control group （ t = 7. 235, 8. 883, P 〈 0.05 ）. The protein expression of P-AKT in the transfection group was 0.21 ± 0.03, which was significantly lower than 0.93 _± 0.13 of the blank control group and 0.91 ± 0.12 of the negative control group （t = 9. 347, 9. 802, P 〈 0.05）. The expressions of Caspase-3 and Caspase-9 of the transfection group were 0.86 ±0.11 and 0.87-±0.12, which were significantly higher than 0.16 ±0.03 and 0.18 ± 0.04 of the negative control group, and 0.15 ±0.02 and 0.16 ±0.03 of the blank control group （t = 10. 634, 10. 999, 9.448, 9. 942, P 〈 0.05）. The apoptotic rate of the MKN28 cells of the treated group was 28.60% ±_ 4.50% , which was significantly higher than 0.12% ± 0.06% of the control group （ t = 10. 961, P 〈 0.05 ）. The protein expression of PI3K and P-AKT of the treated group were 0. 18 ± 0.02 and 0. 11 ± 0.01, which were significantly lower than 0.93± 0.14 and 0.90 ± 0.12 of the control group （ t = 9. 186, 11. 363, P 〈 0.05 ）. The protein expression of PTEN of the treated group was 1.15 _± 0.15, which was significantly higher than 0.21 ± 0.08 of the control group （t = 9. 577, P 〈 0.05 ）. The relative expressions of Caspase-3 and Caspase-9 of the treated group were 0.86 ：t：0.12 and 0.88 0.11, which were significantly higher than 0.25 ±0.02 and 0.21 ±0.03 of the control group （t = 8. 685, 10. 178, P 〈 0.05）. Conclusions Over-expression of PTEN may enhance the apoptosis of gastric cancer cells through inhibition of PI3K/AKT pathway. Inhibition of PI3K can enhance the expression of PTEN. PI3K and FFEN regulate the apoptosis of gastric cancer cells.
Key words:
Gastric neoplasms ; PTEN ; PI3K; AKT; Apoptosis
Abstract Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life‐threatening disease with a high mortality rate, which was a common complication of fat embolism syndrome (FES). Ursodeoxycholic acid (UDCA) has been reported to exert potent anti‐inflammatory effects under various conditions. In vivo , perinephric fat was injected via tail vein to establish a rat FES model, the anti‐inflammatory effects of UDCA on FES‐induced lung injury were investigated through histological examination, ELISA, qRT‐PCR, Western blot and immunofluorescence. In vitro , human lung microvascular endothelial cells (HPMECs) were employed to understand the protective effects of UDCA. The extent of ALI/ARDS was evaluated and validated by reduced PaO 2 /FiO 2 ratios, increased lung wet/dry (W/D) ratios and impaired alveolar‐capillary barrier, up‐regulation of ALI‐related proteins in lung tissues (including myeloperoxidase [MPO], vascular cell adhesion molecule 1 [VCAM‐1], intercellular cell adhesion molecule‐1 [ICAM‐1]), elevated protein concentration and increased proinflammatory cytokines levels (TNF‐α and IL‐1β) in bronchoalveolar lavage fluid (BALF). Pre‐treatment with UDCA remarkably alleviated these pathologic and biochemical changes of FES‐induced ALI/ARDS; our data demonstrated that pre‐treatment with UDCA attenuated the pathologic and biochemical changes of FES‐induced ARDS, which provided a possible preventive therapy for lung injury caused by FES.
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by diffuse inflammation of the lung parenchyma and refractory hypoxemia. Butorphanol is commonly used clinically for perioperative pain relief, but whether butorphanol can regulate LPS-induced alveolar macrophage polarization is unclear. In this study, we observed that butorphanol markedly attenuated sepsis-induced lung tissue injury and mortality in mice. Moreover, butorphanol also decreased the expression of M1 phenotype markers (TNF-α, IL-6, IL-1β and iNOS) and enhanced the expression of M2 marker (CD206) in alveolar macrophages in the bronchoalveolar lavage fluid (BALF) of LPS-stimulated mice. Butorphanol administration reduced LPS-induced numbers of proinflammatory (M1) macrophages and increased numbers of anti-inflammatory (M2) macrophages in the lungs of mice. Furthermore, we found that butorphanol-mediated suppression of the LPS-induced increases in M1 phenotype marker expression (TNF-α, IL-6, IL-1β and iNOS) in bone marrow-derived macrophages (BMDMs), and this effect was reversed by κ-opioid receptor (KOR) antagonists. Moreover, butorphanol inhibited the interaction of TLR4 with MyD88 and further suppressed NF-κB and MAPKs activation. In addition, butorphanol prevented the Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF)-mediated IFN signaling pathway. These effects were ameliorated by KOR antagonists. Thus, butorphanol may promote macrophage polarization from a proinflammatory to an anti-inflammatory phenotype secondary to the inhibition of NF-κB, MAPKs, and the TRIF-mediated IFN signaling pathway through κ receptors.
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