ABSTRACT
Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling, in which hyperproliferation of pulmonary artery smooth muscle cells (PASMCs) plays an important role. The cysteine 674 (C674) in the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) is the critical redox regulatory cysteine to regulate SERCA2 activity. Heterozygous SERCA2 C674S knock-in mice (SKI), where one copy of C674 was substituted by serine to represent partial C674 oxidative inactivation, developed significant pulmonary vascular remodeling resembling human PH, and their right ventricular systolic pressure modestly increased with age. In PASMCs, substitution of C674 activated inositol requiring enzyme 1 alpha (IRE1α) and spliced X-box binding protein 1 (XBP1s) pathway, accelerated cell cycle and cell proliferation, which reversed by IRE1α/XBP1s pathway inhibitor 4μ8C. In addition, suppressing the IRE1α/XBP1s pathway prevented pulmonary vascular remodeling caused by substitution of C674. Similar to SERCA2a, SERCA2b is also important to restrict the proliferation of PASMCs. Our study articulates the causal effect of C674 oxidative inactivation on the development of pulmonary vascular remodeling and PH, emphasizing the importance of C674 in restricting PASMC proliferation to maintain pulmonary vascular homeostasis. Moreover, the IRE1α/XBP1s pathway and SERCA2 might be potential targets for PH therapy.
ABSTRACT
Objective To evaluate the clinical value of endoscopic ultrasonography and CT in the diagnosis of patients with pancreatic and periampullary tumors.Methods From February 2010 to January 2016,89 patients with suspected pancreatic and periampullary tumors in Yinzhou Hospital Affiliated to Medical College of Ningbo University were selected in this study.Endoscopic ultrasonography and CT were performed in 89 patients.Endoscopic ultrasonography and CT examination results were compared with surgical and pathological results ,and the sensitivity, specificity and accuracy of the two methods were recorded and compared.Results By pathological examination , 69 cases were diagnosed as pancreatic and periampullary tumors.The sensitivity of endoscopic ultrasonography was 95.65%(66/69),the specificity was 95.00%(19/20),and the accuracy was 95.51%(85/89).The sensitivity of CT diagnosis was 85.51%(59/69),and the specificity was 90.00%(18/20),and the accuracy was 86.52%(77/89).The sensitivity and accuracy of endoscopic ultrasonography were significantly higher than those of CT ,and the differences were statistically significant (χ2＝4.161,4.395,P ＝0.041,0.036).And there was no statistically significant difference in the specificity of endoscopic ultrasonography and CT (χ2＝0.360,P＝0.548).Conclusion Endoscopic ultrasonography and CT examination have high specificity in the diagnosis of patients with pancreatic and periampullary tumors,however,the sensitivity and accuracy of endoscopic ultrasonography are higher than CT ,the clinical appropriate diagnostic methods can be chosen according to the actual condition of the patients .
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Objective To investigate the significance of serum Let-7b in prostate cancer (PCa). Methods From July 2015 to September 2016, 72 patients with PCa (PCa group) and 34 healthy people (control group) were selected. The Let- 7b was detected by Western blot and fluorescence quantitative polymerase chain reaction (PCR), and the Let-7b was compared between 2 groups. Results The Let-7b in PCa group was significantly lower than that of control group (0.81 ±0.38 vs.1.31 ±0.34), and there was statistical difference (P<0.01). In PCa group, the Let- 7b in patients with TNM T3 and T4 stage was significantly lower than that in patients with TNM T1 and T2 stage (0.74 ± 0.39 vs. 0.88 ± 0.38), and there was statistical difference (P<0.05); the Let-7b in patients with hormone dependence was significantly higher than that in patients with hormone resistance (1.03 ± 0.40 vs. 0.64 ± 0.27), and there was statistical difference (P<0.05). Receiver operating characteristics curve analysis result showed that Let-7b sensitivity and specificity were 72.2％ and 88.2％ in the diagnosis of PCa. Conclusions Let-7b can indicate the degree of malignancy of the tumor and the hormone resistance. For patients with the high risk of early diagnosis of refractory PCa, the patients′ individualized treatment plan could be adjusted.
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Objective To study the expression and clinical significance of miR-183-5p, TβRⅠ and TβRⅡ in esophageal squamous cell carcinoma (ESCC). Methods The mRNA and protein expression of miR-183-5p, TβRⅠ and TβRⅡ were examined in ESCC cell lines ECA-109, TE-1, normal esophageal epithelial cells, tumor tissues and tumor-free tissues from 72 ESCC patients. Their clinical significance and the relationship between miR-183-5p and the latter two were analyzed. The effects of miR-183-5p on the expression of TβRⅠand TβRⅡ in ECA-109 cells and the cell functions of ECA-109 were also investigated. Results Compared with the normal esophageal epithelia cells, ESCC cell lines TE-1 and ECA-109 were statistically characterized by a high expression of miR-183-5p (all P<0.05) and low expression of TβRⅠand TβRⅡ(all P<0.05). The expression of miR-183-5p in ESCC tissues was higher than that in adjacent normal tissues, while the expressions of TβRⅠ and TβRⅡ were lower (all P< 0.05). The expression of miR-183-5p was closely related to sex, tumor differentiation, tumor staging, distant metastasis, lymphatic metastasis, and tumor location (all P<0.05). TβRⅠlevel was associated with sex, lymph node metastasis and tumor size (all P<0.05). Experimental data showed the negative correlation between the expression of miR-183-5p and TβRⅠin ESCC tissues (r= -0.521, P< 0.05). Over expression of miR-183-5p significantly inhibited the expression of TβRⅠ in ECA-109 cells (P< 0.05) and promoted the growth, invasion and metastasis of ECA-109 cells (P< 0.05). Low expression of miR-183-5p significantly promoted the expression of TβRⅠ in ECA-109 cells (P< 0.05), and suppressed the growth, invasion and metastasis of ECA-109 cells (P< 0.05). There was no significant change in the expression of TβRⅡ in the transfection experiments. Conclusion MiR-183-5p is closely related to the abnormal expression of TβRⅠ, which may exert an important role in the progression of lymphatic metastasis.