1.Role of paxillin in colorectal carcinoma and its relationship to clinicopathological features.
Hongfang YIN ; Quanwen ZHANG ; Xin WANG ; Ting LI ; Yuanlian WAN ; Yucun LIU ; Jing ZHU
Chinese Medical Journal 2014;127(3):423-429
BACKGROUNDColorectal carcinoma is one of the most common malignant tumors. Despite advances in therapy, mortality is still very high. The aim of this study was to evaluate the expression of paxillin in the human colon adenocarcinoma cell line SW480 and its role in cell cycle and apoptosis. We also investigated the expression of paxillin in colorectal carcinoma tissues and its relationship to clinicopathological features and survival.
METHODSPaxillin short hairpin RNA (shRNA) was constructed and transfected into the colon adenocarcinoma cell line SW480. The influence of paxillin shRNA on the cell cycle and cell apoptosis was analyzed by flow cytometry. Immunohistochemistry staining was used to assess the expression of paxillin and its association with the expression of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, p53 and Bcl-2 in 102 patients with primary colorectal carcinoma. Western blotting was also used to investigate the expression of paxillin. Medical records were reviewed and a clinicopathological analysis was performed.
RESULTSIn vitro, the percentage of cells in S phase was (45.23±1.05)%, (43.53±1.23)%, and (36.13±0.57)% in the blank control group, negative control group, and paxillin shRNA group respectively. It was significantly decreased in the paxillin shRNA group (P = 0.000). The early apoptosis index of the paxillin shRNA group (17.2±1.18%) was significantly increased compared to the control shRNA group ((13.17±1.15)%, P = 0.013). Paxillin was positive in 71 (69.6%) patients, and it was found to be overexpressed in tumor tissues compared with normal adjacent tissues. Paxillin positive rate was higher in patients who are less than 50-years old (100.0% vs. 65.6%, P = 0.016). Paxillin expression was associated with a high histologic grade of carcinoma (81.4% vs. 61.0%, P = 0.031), a high rate of regional lymph node metastasis (22.5% vs. 13.0%, P = 0.031), mesenteric artery lymph node metastasis (100.0% vs. 64.8%, P = 0.008), distant metastasis (94.1% vs. 64.7%, P = 0.016) and a high Tumor Node Metastasis (TNM) stage (94.1%, 73.2%, 60.0%, and 50%, P = 0.030). Multivariate analyses revealed that recurrence was associated with the rate of regional lymph node metastasis (P = 0.001) and paxillin expression (P = 0.024). Multivariate analysis indicated that the overall survival is related to the TNM stage (P = 0.000).
CONCLUSIONSIn vitro, paxillin may promote cell proliferation and inhibit apoptosis in SW480 cells. Paxillin may be a potential metastasis predictor, and an independent prognosis factor of recurrence. It may also be related to poor patient outcomes, but was not an independent predictor of survival.
Apoptosis ; genetics ; physiology ; Biomarkers, Tumor ; genetics ; metabolism ; Carcinoembryonic Antigen ; metabolism ; Cell Cycle ; genetics ; physiology ; Cell Line, Tumor ; Cell Proliferation ; Colorectal Neoplasms ; genetics ; metabolism ; Female ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Male ; Paxillin ; genetics ; metabolism ; RNA, Small Interfering ; genetics
2. The clinical application of ultra-pulsed CO2 laser skin abrasion combined with micro-skin grafting in the treatment of skin depigmentation
Shuai CHEN ; Minghuo XU ; Ping JIANG ; Huifeng SONG ; Quanwen GAO ; Fang WANG ; Ruijuan ZHANG ; Jiajia ZENG
Chinese Journal of Plastic Surgery 2019;35(5):441-446
Objective:
To explore the clinical application of ultra-pulsed CO2 laser skin abrasion combined with micro-skin graft in the treatment of skin depigmentation.
Methods:
From January 2010 to June 2014, depigmented skin specimens were used for ultra-pulsed CO2 laser skin abrasion treatment, at 0, 10, 20, 30, 40, 50, 60 mJ. HE stain was performed to observe the abrasion depth under the 100 times microscope view. The most appropriate parameter was set to completely remove the epidermis, and leave dermis undamaged. From January 2011 to December 2017, 16 patients with skin depigmentation, 12 males and 4 females, aged 12-47 years, were treated with super-pulsed carbon dioxide laser and autologous microdermis transplantation. At 1, 3, 6 and 12 months after the operation, patients′ photos were record. The color improvement was analyzed using Image-Pro Plus 6.0 software.
Results:
The laser energy for complete epidermis removal is different at different sites. It is 50 mJ for back skin, 40 mJ for face and hand skin and 30 mJ for neck skin. After one year of follow-up, there was no hypertrophy scar caused by over-abrasion in all 16 patients. Combined with the micro-skingrafting, 15 patients with skin depigmentation were completely resolved, with more than 90%color improvement rate. The improvement rate was 75% in a patient with un-uniform appearance, due to part failure of micro-skin graft. The neck movement and uncertain fixation were the reasons.
Conclusions
The appropriate energy parameters can control the abrasion depth to avoid the hypertrophic scar. Combined with micro-skin graft, the depigmentation area can be improved with uniform color and reliable effect.
3. Subunit strategy for perineal defect reconstruction
Hao NIU ; Huifeng SONG ; Minghuo XU ; Quanwen GAO ; Baoguo CHEN ; Shuai CHEN ; Jue WANG ; Fang WANG ; Jiang WU ; Ruijuan ZHANG
Chinese Journal of Plastic Surgery 2019;35(5):436-440
Objective:
To explore the subunit strategy for perineal defect reconstruction and flap selection.
Methods:
This is a respective study of 21 patients, with perineal defect, during January 2008 to December 2018. All patients were admitted to the fifth section of Burn and Plastic Surgery in the Fourth Medical Center of the People′s Liberation Army General Hospital. There were 10 males and 11 females, aged from 4 to 68 years old, with the mean age of 26.4 years. The causes of injury included burn (
4.Non-canonical STING-PERK pathway dependent epigenetic regulation of vascular endothelial dysfunction via integrating IRF3 and NF-κB in inflammatory response.
Xuesong LI ; Xiang CHEN ; Longbin ZHENG ; Minghong CHEN ; Yunjia ZHANG ; Ruigong ZHU ; Jiajing CHEN ; Jiaming GU ; Quanwen YIN ; Hong JIANG ; Xuan WU ; Xian JI ; Xin TANG ; Mengdie DONG ; Qingguo LI ; Yuanqing GAO ; Hongshan CHEN
Acta Pharmaceutica Sinica B 2023;13(12):4765-4784
Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.