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Cheng P.,Huazhong University of Science and Technology | Chen K.,Huazhong University of Science and Technology | Yu W.,Huazhong University of Science and Technology | Gao S.,Huazhong University of Science and Technology | And 3 more authors.
Journal of the Neurological Sciences | Year: 2015

Current treatments to restore neurological deficits caused by axonal disconnection following central nervous system (CNS) injury are extremely limited. Protein phosphatase 2A (PP2A), one of the main serine-threonine phosphatases in mammalian cells, dephosphorylates collapsin response mediator protein-2 (CRMP2) in the developing CNS. In our study, we found that the major CNS inhibiting substrates, including chondroitin sulfate proteoglycans (CSPGs) and myelin associated glycoproteins (MAG), activated epidermal growth factor receptor (EGFR), but inactivated PP2A and downstream CRMP2. Both EGFR inactivation and PP2A activation promoted axon elongation in vitro in the presence of inhibitory substrates. EGFR blockage by AG1478 selectively attenuated the inactive form of PP2A in pY307 phosphorylation, thus increasing PP2A activity. EGFR activation by EGF attenuated PP2A activity, whereas mutation of Y307 to phenylalanine abolished the effect. Furthermore, PP2A activity was down-regulated immediately after spinal cord injury (SCI) in rats. Chronic application of d-erythro-sphingosine (DES), the PP2A agonist, to spinal cord-lesioned rats enhanced the activity of this phosphatase and dephosphorylated CRMP2 around the lesion. PP2A activation induced significant axon sprouting in the lesioned spinal cord and promoted function recovery after SCI. These findings suggest that PP2A works downstream of EGFR and dephosphorylates CRMP2 after CNS injury. Therefore, therapies targeting PP2A may be effective following SCI. © 2015 Elsevier B.V.

Cheng H.,Xian Jiaotong University | Zhan N.,Wuhan University | Ding D.,Hubei Maternity and Child Health Hospital | Liu X.,Soochow University of China | And 3 more authors.
Journal of Investigative Dermatology | Year: 2015

Previously, tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) had been known to be an inducer of apoptosis of keratinocytes by engaging the Fn14 receptor. However, the high-risk human papillomavirus (HPV) infection confers a proliferation advantage on keratinocytes that may consequently harbor tumorigenicity. This study was designed to investigate the cross-talk in keratinocytes between TWEAK/Fn14 signaling and HPV type 16 infection, which may cooperate in regulating cell-cycle progression. TWEAK and Fn14 expression was determined in anogenital warts and normal skin. Both primary keratinocytes and HaCaT cells were transfected with HPV16 E6/E7 genes. The results showed that Fn14 is highly expressed upon HPV16 transfection and accompanied by an increase in Ras GTPase activity and TNF-receptor-associated factor 2 (TRAF2) expression. Moreover, the E6/E7-transfected keratinocytes exhibit a shift of TNF receptor profile from type 1 to type 2 and weakened apoptotic response to TNF-α stimuli, when compared with the normal control. Surprisingly, significant increase in proliferation but not apoptosis was seen in E6/E7-positive keratinocytes, as TWEAK was additionally supplemented. In conclusion, the HPV16 infection in keratinocytes causes a switch of apoptotic to proliferative fate under TWEAK/Fn14 interaction, possibly by favoring Ras and TRAF2 activation and modulating TNF receptor expression.

Zhao S.,Qingdao University | Deng J.,Kunming Maternal and Child Health Hospital | Wang Y.,Hubei Maternity and Child Health Hospital | Bi S.,University of Sichuan | And 8 more authors.
Patient Preference and Adherence | Year: 2014

Background: Although surveys conducted in Western countries have shown that the levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena®) is well accepted by European women, its acceptance by Chinese women is not yet clearly known. The purpose of this study was to analyze the experiences and levels of satisfaction with Mirena among Chinese women living in 12 different cities.Methods: In total, 1,021 women who attended 21 medical centers for insertion of Mirena were invited to complete a questionnaire regarding their contraceptive decision at baseline (preinsertion), and two further questionnaires on their experience and satisfaction with Mirena at 3–6 months and 1 year after insertion.Results: At baseline, 36% of women self-reported heavy or very heavy menstrual bleeding, while 41% reported normal bleeding. The majority of women (98%) were satisfied with the preinsertion counseling, during which contraceptive reliability was identified as the most important reason for considering Mirena. Continuation rates for Mirena were 99% at 3–6 months and 93% at 12 months after insertion, and most women (92% and 93%, respectively) had less bleeding at these times. The percentage of women who rated Mirena as better than their previous contraceptive method was 63%. Overall, around 90% of respondents were very satisfied or rather satisfied with Mirena, and 64% stated that they would recommend it to their friends.Conclusion: These data suggest that continuation and satisfaction rates with Mirena were very high, and that the device is well accepted by Chinese women. © 2014 Zhao et al.

Cheng H.,Xian Jiaotong University | Xu M.,Xian Jiaotong University | Liu X.,Soochow University of China | Zou X.,Hubei Maternity and Child Health Hospital | And 2 more authors.
Experimental Dermatology | Year: 2016

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) has been reported to induce keratinocyte apoptosis in vitro by engaging its sole receptor of fibroblast growth factor-inducible 14 (Fn14). In this study, we explored the role of TWEAK/Fn14 pathway in the growth of psoriatic keratinocytes that is, however, characterized by suppressed apoptotic cell death. Skin tissues from the patients with psoriasis or healthy donors were determined for TWEAK and Fn14 expression, and primary keratinocytes were evaluated under the stimulation of psoriatic proinflammatory cytokines or plus TWEAK. The results showed that both TWEAK and Fn14 were highly expressed in psoriatic skins. Moreover, the stimulation of psoriatic cytokines enhanced Fn14 expression by keratinocytes in vitro, which expressed TNF receptor 2 predominantly and proliferated increasingly with the addition of TWEAK. Furthermore, TWEAK stimulation enhanced the synthesis of survivin, inhibitor of apoptosis protein 2 and cellular FLICE-inhibitory protein in lesional keratinocytes. Therefore, TWEAK/Fn14 interaction prefers to enhance proliferation but not apoptosis of keratinocytes under psoriatic inflammation. The activation of nuclear factor-κB signalling-dependent anti-apoptotic proteins and biased expression of TNF receptors may be responsible for such a novel principle in keratinocytes under psoriatic inflammation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Zou X.-Y.,Hubei Maternity and Child Health Hospital | Ding D.,Hubei Maternity and Child Health Hospital | Zhan N.,Wuhan University | Liu X.-M.,Soochow University of China | And 2 more authors.
Journal of Investigative Dermatology | Year: 2015

Glyoxalase I (GLO1) is a methylglyoxal detoxification enzyme being implicated in the progression of multiple malignancies. However, currently, the role of GLO1 in human nonmelanoma skin tumors remains unclear. To explore the expression of GLO1 in cutaneous neoplasms and its role in the pathogenesis of skin cancers, we determined the GLO1 expression in multiple subtypes of cutaneous neoplasms and cell lines harboring different tumorigenicity. Also, the GLO1 siRNA transfection was performed in squamous cell carcinoma (SCC)-13 cells or SCC in the xenograft model. The results show that GLO1 was overexpressed by SCC, basal cell carcinoma, and verrucous carcinoma but weakly expressed by several benign neoplasms. Human papilloma virus 16 E6/E7-transfected keratinocytes expressed more GLO1 than did normal keratinocytes, although both of them had lower levels of GLO1 than SCC-13 cells. Moreover, the knockdown of GLO1 by siRNA was related to enhanced apoptosis of SCC-13 cells in the presence of tumor necrosis factor-related apoptosis-inducing ligand and inhibited cell invasion and migration, which was mirrored by the suppressed growth of SCC xenografts in mice. Finally, the GLO1 regulation of SCC-13 cells might be relevant to methylglyoxal-induced p53 translocation. Therefore, GLO1 is prevailingly expressed in cutaneous neoplasms of higher malignancy and contributes to the progression of SCC. © 2015 The Society for Investigative Dermatology.

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