Pulmonary hypertension is a kind of progressive pulmonary vascular diseases in which there is excessive vasoconstriction and abnormal pulmonary vascular remodeling, and then a gradual increase in pulmonary arterial pressure, and it eventually leads to right ventricular failure and even death. The pathogenesis of pulmonary hypertension is still uncertain, but some studies suggest that Hippo pathway or some components of the Hippo pathway may be involved in the progress of pulmonary hypertension. In this review, we describe the mechanism of the Hippo pathway or some components of the Hippo pathway in the progress of pulmonary hypertension.
Objective To investigate the therapeutic effects of retinal angiomatosis in different clinical stages. To discuss the indication of vitrectomy for retinal hemangioblastoma. Methods The clinical data of 22 cases (33 eyes) were retrospectively analyzed. The retinal hemangiomas were divided into 5 stages according to their degrees of development from simple angioma without vessel dilation to feeder vessel dilation and intra-retinal exudates, local retinal detachment, massive retinal detachment and co mplication occurrence in proper order. The methods of treatment were laser photo coagulation, trans－scleral cryotherapy and vitrectomy. 13 eyes were treated with laser photocoagulation, 5 eyes with cryotherapy combined with laser and 11 eye s with vitrectomy. Tumor resection and silicone oil tamponade was performed in 3 eyes during vitrectomy. The patients were followed up for 46 months on average. Visual acuity (VA), the condition of the hemangioma and retina was compared pre- and post-operation respectively. Results In all 13 eyes treated with laser photocoagulation the hemangiomas regressed and the retina remained attached. VA improved in 2 eyes, and remained unchanged in 11 eyes. Cryother apy combined with laser photocoagulation was performed on 5 eyes. In this group, 4 eyesprime; hemangiomas regressed and no new hemangiomas occurred, proliferative vitreous retinopathy and vitreous hemorrhage was observed in 1 eye which vitrecto my was performed later. VA improved in 2 eyes, unchanged in 2 eyes and decreased in 1 eye. In the 11 eyes treated with vitreoretinal surgery, new hemangiomas wa s found in 1 eye, exudative retinal detachment was caused by hemangiomas in 2 eyes, proliferative vitreous retinopathy was observed in 2 eyes, and the retina re mained attached in 8 eyes. VA improved in 3 eyes, unimproved in 3 eyes, and decreased in 5 eyes. In the 3 eyes with surgical resection of retinal hemangioma during vitrectomy, 2 eyesprime; retina remained attached, 1 eye had exu dative retinal detachment and no new hemangiomas occurred. VA improved in 2 eyes and decreased in 1 eye. Conclusions Laser photocoagulation or combined with cryotherapy is effective in treating the hemangiomas in early stage. Vitrectomy is advisable for late stage of retinal angiomatosis, especially with vitreous hemorrhage, epiretinal membrane, proliferation and large scale of r etinal detachment. Surgical resection of isolated large retinal hemangioblastoma may be useful for selected patients. (Chin J Ocul Fundus Dis,2008,24:107-110)
ObjectiveTo investigate regulation mechanism of glypican-3 (GPC3) on Hippo signaling pathway and its effects on biological behavior of hepatocellular carcinoma Huh7 cells. MethodsShort hairpin RNAs (shRNA) targeting GPC3 and Yes-associated protein 1 (YAP1) genes were constructed. All of the shRNAs were transfected into Huh7 cells by liposome transfection in order to screen out the stable expression cell lines. The expressions of GPC3 and YAP1 in Huh7 cells were detected by PCR and Western blot in order to screen out the effective shRNAs. The proliferation, invasion, and apoptosis of Huh7 cells were detected by Edu cell proliferation assay, transwell, and flow cytometry. GPC3 shRNA transfection experiments were divided into 6 groups:non-transfection group, empty vector group, GPC3-714-shRNA group, GPC3-647-shRNA group, GPC3-1718-shRNA group, and GPC3-2134-shRNA group. YAP1 shRNA transfection experiments were divided into 6 groups:non-transfection group, empty vector group, YAP1-906-shRNA group, YAP1-1363-shRNA group, YAP1-1666-shRNA group, and YAP1-2895-shRNA group. GPC3 regulation experiments were divided into 5 groups:non-transfection group, empty vector group, GPC3-1718-shRNA group, GPC3-1718-shRNA+ rhYAP1 group, and YAP1-1666-shRNA group. Results① GPC3-1718-shRNA and YAP1-1666-shRNA plasmids were successfully constructed to silence the expressions of GPC3 and YAP1. ② The expressions of GPC3 mRNA and protein in each transfection group were significantly lower than those in the non-transfection group (P<0.05) and the empty vector group (P<0.05), while which in the GPC3-1718-shRNA group was significantly lower than those in all the other transfection groups (P<0.05). The expressions of YAP1 mRNA and protein in each transfection group were significantly lower than those in the non-transfection group and empty vector group (P<0.05), while which in the YAP1-1666-shRNA group was significantly lower than those in all the other transfection groups (P<0.05). ③ The expressions of YAP1 mRNA and protein in the GPC3-1718-shRNA group and the YAP1-1666-shRNA group were significantly lower than those in the non-transfection group (P<0.05) and the empty vector group (P<0.05), while which in the GPC3-1718-shRNA+rhYAP1 group were significantly higher than those in the GPC3-1718-shRNA group (P<0.05) and the YAP1-1666-shRNA group (P<0.05). ④ Compared with the non-transfection group and the empty vector group, the abilities of cell proliferation and invasion in the GPC3-1718-shRNA group and the YAP1-1666-shRNA group were significantly decreased, and the cell apoptosis was significantly increased (P<0.05); The cell proliferation, invasion, and apoptosis in the GPC3-1718-shRNA+rhYAP1 group were significantly improved (P<0.05). ConclusionGPC3 is likely to affect biological behavior of hepatocellular carcinoma Huh7 cells through regulation of YAP1 in Hippo signaling pathway.
The classical Hippo pathway leads to the phosphorylation of downstream effector molecules Hippo-Yes-associated protein (Yap) and transcriptional coactivator PDZ-binding motif (Taz) serine sites through a kinase response, thereby promoting cell proliferation, controlling cell polarity, changing cytoskeleton, it plays an important regulatory role in various pathophysiological processes such as epithelial-mesenchymal transition and inhibition of cell contact. Studies have shown that Yap/Taz can affect the progression of vitreoretinal diseases, opening up new prospects for the pathogenesis and clinical treatment of diabetic retinopathy, proliferative vitreoretinopathy, and retinal ischemia-reperfusion injury. Exploring the molecular mechanism of Yap/Taz provides a possible therapeutic target for future research in the treatment of retinal fibrosis diseases such as diabetic retinopathy and proliferative vitreoretinopathy. At the same time, regulating the activity of local Yap/Taz in the retina will also become an effective therapeutic target for damage-repair in retinal ischemia-reperfusion injury. However, Yap inhibitors have potential retinal toxicity and are still in the preclinical development stage. Further research on the mechanism of action and clinical safety of Yap inhibitors will provide new methods for the treatment of retinal diseases.
Objective To investigate the expression of SAPCD2 in the lung adenocarcinoma cells, and to study the effect of SAPCD2 regulating Hippo signaling pathway on the proliferation, invasion, migration and apoptosis of the lung adenocarcinoma cells and its mechanism. Methods Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression levels of SAPCD2 mRNA and protein in four types of lung cancer cells (HCC827, H1650, SK-MES-1, A549) and human normal lung epithelial cells (BESA-2B), respectively. Then, lung cancer cells with relatively high levels of SAPCD2 expression were selected for subsequent experiments. The experiment cells were divided into a normal control group (NC group), a si-SAPCD2 group, and a pathway inhibitor group (si-SAPCD2+XMU-MP-1 group). Firstly, SAPCD2 mRNA was silenced using small interfering RNA (siRNA) technology, and then qRT-PCR was used to detect the expression of SAPCD2 in transfected lung cancer cells; using clone plate assay to detect the proliferation of lung cancer cells after silencing; using flow cytometry to detect the apoptosis of lung cancer cells after silencing; observe the number of lung cancer cells at different stages through cell cycle experiments; then Transwell experiment was used to analyze the effect of silencing SAPCD2 on the migration and invasion of lung cancer cell migration. Finally, Western blot was used to detect the expression of ki-67, Bcl-2, Caspase-3, NF2, P-MST1, P-LATS1, P-YAP, YAP, and TAZ proteins.Results SAPCD2 had the highest expression level in lung adenocarcinoma A549 cells (P<0.01). Silencing SAPCD2 significantly decreased the proliferation ability of A549 cells (P<0.01), inhibited their migration (P<0.05) and invasion (P<0.01), and promoted A549 cell apoptosis (P<0.01); more than half of the cells remained in the G0/G1 phase. Compared with the NC group, A549 cells showed a significant increase in G0/G1 phase cells (P<0.01), a significant decrease in G2/M and S phase cells (P<0.01), and a significant increase in the proportion of early apoptotic cells (P<0.01). Western blot results showed that silencing SAPCD2 down-regulated the expression of ki-67, Bcl-2, YAP, and TAZ proteins compared to the NC group (P<0.01), and up-regulated the expression of Caspase-3, NF2, P-MST1, P-LATS1, and P-YAP proteins (P<0.01). Conclusions The expression of SAPCD2 in lung adenocarcinoma A549 cells is significantly higher than that in normal lung epithelial cells (BESA-2B), which promotes the proliferation, migration and invasion of A549 cells and inhibits apoptosis. The mechanism may be related to the inhibition of Hippo signaling pathway.
ObjectiveTo summarize the research progress of Hippo signaling pathway in triple negative breast cancer (TNBC). MethodLiteratures about studies the role of Hippo signaling pathway in cancer stem cells, epithelial-mesenchymal transformation, tumorigenesis and development, distant metastasis, treatment resistance, and treatment strategies were retrieved. ResultsIn TNBC, overexpression of Yes-associated protein and PDZ-binding motif could promote the development of tumor stem cells, induce epithelial-mesenchymal transformation of TNBC cells, and promote tumor development, distant metastasis, and chemotherapy resistance. ConclusionHippo/Yes-associated protein axis plays an important role in carcinogenesis and progression of TNBC, and targeting Hippo signaling pathway might be a potential therapeutic target for TNBC.
Objective To explore the expression of yes-associated protein 1 (YAP1), as a key protein of Hippo signal pathway, in rats with brain injury. Methods A total of 18 Sprague Dawley rats were randomly divided into three groups: normal group, sham operation group and brain injury group. The expression of YAP1 in rats with brain injury was detected by immunochemistry, quantitative polymerase chainreaction and Western blotting. Result Seventy-two hours after the brain injury, the expression level of YAP1 in protein and gene increased significantly in brain injury group, compared with those in the normal and sham operation group (P<0.05). Conclusion The expression of YAP1 increases in rats with brain injury, which maybe a new target for therapy.
ObjectiveTo investigate the effectiveness of Bernese osteotomy for the treatment of developmental dysplasia of the hip (DDH) in adults. MethodsBetween August 2012 and April 2014, 16 patients with DDH were treated with Bernese osteotomy by S-P approach, and the clinical data were retrospectively analyzed. There were 4 males and 12 females with an average age of 27.8 years (range, 18-35 years). The left side was involved in 6 cases and the right side in 10 cases. The visual analogue scale (VAS) score was 4.8±0.5, and the Harris hip score was 81.2±5.4. The lateral center edge (CE) angle (the angle between the vertical center of the femoral head and the lateral edge of the acetabulum) was (6.5±8.7)°;the horizontal tilt angle was (25.6±5.9)°;and the femoral head extrusion index was 36.5%±6.5%. According to the Tonnis osteoarthritis classification, 12 hips were rated as Grade 0, 3 hips as Grade I, and 1 hip as Grade II. ResultsThe operation time was 90-135 minutes;the intraoperative blood loss was 400-800 mL;10 cases accepted blood transfusion and the amount of blood transfusion was 200-600 mL;the postoperative drainage volume was 100-300 mL;and the hospitalization time was 7-12 days. All the cases achieved primary healing of incision with no early complications. Two cases had numb in the lateral femoral cutaneous nerve innervating area. All patients were followed up 12-26 months (mean, 20 months). The X-ray examination showed osseous healing at osteotomy site, and the healing time was 12-16 weeks (mean, 13.5 weeks). No acetabulum fracture, heterotopic ossification, osteonecrosis, and internal fixation loosening occurred during follow-up. No progression of osteoarthritis or acetabular cystic change was observed. At last follow-up, the lateral CE angle was (27.7±6.8)°;the horizontal tilt angle was (16.2±4.8)°;the femoral head extrusion index was 19.7%±5.3%;VAS score was 0.8±0.3;the Harris hip score was 96.8±6.7;and all showed significant differences when compared with preoperative ones (P<0.05). ConclusionFor DDH adults, Bernese osteotomy can effectively increase the acetabulum tolerance, improve the joint function, and slow progress in osteoarthritis, and the short-term effectiveness is satisfactory.
Objective To evaluate the clinical valueof the revision of total hip replacement(THR), to analyse the reason of the rev isions, and to discuss the main difficulties and measures to manage it.Methods From June 1998 to January 2002, 15 cases (15 hips) were revised on totalhip replacement. The reasons for revision in the cases were as follows:failure of primary operative techenique, loosening and sinking of the components, displacement of the prosthesis, erosion of the acetabulum, as well as fracture of the femoral stem. The main difficulties of the revision were:poor health condition of the patients; the remove of the prosthesis of the primary THR,especially the broken femoral stem and the cements; the loss of localbone. The measures to remove the broken femoral stem were described.ResultsAll cases were followed up 2.4 years on average: 2 patients died from heart disease and cerebrovascular disease respectively, while the good results were achieved in the others.No infection, dislocation, loosening, and other complications occurred. The good effects were related with following factors:mild degree of illness; no severe bone defect; most of the first femoral head replacement.Conclusion The revision of THRis a more difficult operation, so that the special instrument and equipment andoperative experience are required.
Objective To evaluate the values of magnetic resonance imaging (MRI) in the diagnosis of acetabular labral tears (ALT) by meta-analysis. Methods The studies concerning the diagnosis of ALT tears by using MRI from January 1990 to October 2016 were searched in the databases such as CBM, VIP, WanFang Data, CNKI, PubMed, EMbase, The Cochrane Library and Web of Science. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies by using the QUADAS-2 tool. Then, meta-analysis was performed by using Stata 12.0 software. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (–LR) and the diagnostic odds ratio (DOR) were calculated, and the summary receiver operating characteristic curve (SROC) was drawn and the area under the carve was calculated. Results A total of 25 studies from 21 articles were included, involving 1 123 hips from 1 099 patients. The results of meta-analysis showed that, the pooled Sen, Spe, +LR, –LR, DOR and area under SROC curve of MRI for diagnosing ALT were 0.66 (95% CI 0.38 to 0.86), 0.72 (95% CI 0.47 to 0.89), 2.37 (95% CI 1.18 to 4.67), 0.48 (95% CI 0.25 to 0.92), 4.97 (95% CI 1.60 to 15.47), 0.75 (95% CI 0.71 to 0.79). The pooled Sen, Spe, +LR, –LR, DOR and area under SROC curve of MRA for diagnosing ALT were 0.86 (95% CI 0.80 to 0.90), 0.71 (95% CI 0.55 to 0.83), 2.91 (95% CI 1.77 to 4.80), 0.20 (95% CI 0.13 to 0.32), 14.44 (95% CI 5.80 to 35.95), 0.87 (95% CI 0.84 to 0.90), respectively. Conclusion MRI is efficiency diagnostic method for acetabular labral tears.