Background and Aim. Interleukin-6 (IL-6) modulates neurons–glia crosstalk and subsequently triggers hyperalgesia. This study is aimed at investigating whether the interaction between protein kinase C epsilon (PKCε) and signal transducer and activator of transcription 3 (STAT3) mediated IL-6-induced hyperalgesia and neurocyte activation. Methods. A rat hyperalgesia model was induced using an intraplantar injection of Freund’s complete adjuvant (FCA) or an intrathecal injection of IL-6. Mechanical allodynia was evaluated using von Frey filament tests after intrathecal injections of T-5224 (c-Fos/AP-1 inhibitor), minocycline (Mino, a specific microglia inhibitor), L-2-aminoadipic acid (LAA, an astroglial toxin), PKCε inhibitor peptide, APTSTAT3-9R (STAT3 inhibitor), or anti-IL-6 antibody. The c-Fos, GFAP, Iba-1, PKCε, STAT3, pSTAT3Tyr705 and pSTAT3Ser727, and IL-6 expression at the spinal cord level was assessed by Western blot analysis. The interactive effects of PKCε and STAT3 were determined using immunofluorescence staining and immunoprecipitation in vivo and in vitro. Interleukin-6 promoter activity was examined using luciferase assays. Results. T-5224, Mino, and LAA attenuated FCA- or IL-6-mediated inflammatory pain, with a decrease in c-Fos, GFAP, Iba-1, PKCε, and IL-6 expression. PKCε inhibitor peptide and APTSTAT3-9R reversed FCA-induced nociceptive behavior, while decreasing pSTAT3Ser727, IL-6, c-Fos, GFAP, and Iba-1 expression and PKCε and STAT3 coexpression. Interleukin-6 promoter activity increased in the presence of PKCε and STAT3. The interaction with PKCε increased on phosphorylating STAT3 at Ser727 but not at Tyr705. Conclusion. STAT3 phosphorylation at Ser 727 and the interaction with PKCε contribute to hyperalgesia via the IL-6-mediated signaling pathway, thus regulating neuron–glia crosstalk during inflammatory pain.

Kidney renal clear cell carcinoma (KIRC) is the most common primary renal neoplasms. Currently, there are few molecular indicators and therapeutic targets that can be used in diagnostic and prognostic assessment. In this study, we identified the C19orf10 expression in KIRC specimens and explored the diagnostic and prognostic value of C19orf10 in KIRC using TCGA and CPTAC database. Loss-of- and gain-of- function of C19orf10 was performed to investigate the roles of C19orf10 on KIRC cell viability, proliferation, migration and invasion via CCK-8, Edu incorporation and Transwell assays respectively. C19orf10 was overexpressed in KIRC tissues and the elevated C19orf10 expression was closely associated with clinicopathological characteristics of KIRC including histological grade, TNM stage, metastatic status. Silencing C19orf10 significantly suppressed the viability, proliferation, migration and invasion ability, while overexpression of C19orf10 promoted the progression and malignant phenotype in KIRC cells. Furthermore, C19orf10 exerted its carcinogenic function by regulating ZO-1 and PTEN/Akt signaling pathway. Moreover, the Kaplan–Meier survival analysis, Cox regression analysis and receiver operating curve analysis showed that patients with C19orf10 overexpression have poor survival time. C19orf10 could discriminate KIRC patients with high-risk from low-risk. Taken together, C19orf10 contributes to KIRC development via ZO-1 and PTEN/Akt signaling pathway and C19orf10 could serve as a potential diagnostic and prognostic candidate and therapeutic target of KIRC.

Pregnancy-associated plasma protein A (PAPP-A) is a proteolytic enzyme produced by the placenta. The expression and role of PAPP-A in renal cell carcinoma (RCC) remain elusive. The aim of this study was to investigate the role and the molecular mechanisms of PAPP-A in RCC. Initially, we evaluated the expression of PAPP-A in samples from patients with RCC and cell lines by quantitative PCR, western blot and immunohistochemical staining, and examined the role of PAPP-A in RCC cells by cell viability, colony formation and Transwell assays. Next, we investigated the molecular mechanisms regulating the tumor suppressor function of PAPP-A. Our results demonstrated that PAPP-A is expressed at low levels in RCC tissues and cells. Clinical data analysis revealed a significant correlation between PAPP-A expression and RCC-related death (P < 0.0115). Overexpression of PAPP-A inhibited viability, proliferation, migration and invasion of RCC cells. Furthermore, PAPP-A overexpression significantly increased phosphorylation of c-Jun N-terminal kinase and decreased the expression of cyclin D1, phosphorylated glycogen synthase kinase-3b and b-catenin. This study is the first to report that downregulation of PAPP-A is associated with poor prognosis in patients with RCC. In conclusion, PAPP-A may serve as a novel prognostic marker and potentially as a therapeutic target in patients with RCC.Renal cell carcinoma (RCC) comprises 2% to 3% of all adult malignancies; RCC has had a high incidence rate in recent years and accounts for~80% of primary renal malignancies [1]. Clear cell RCC (ccRCC) accounts for about 80% of RCCs and is the most aggressive subtype of RCC. Partial nephrectomy is the most effective therapeutic method for early and local RCC. However, up to 30% of patients experience development of metastases after surgery [2]. The mechanism of RCC formation and progression remains unclear. Therefore, exploring new targets associated with tumorigenesis may improve the potential therapeutic strategies and the therapeutic response of RCC.

RESUMENEn el contexto de la globalización económica, la internacionalización de la educación superior se perfila como una tendencia que está modificando las agendas de reforma educativa de este nivel en todos los países. En el caso de China, las políticas adoptadas en los años pasados han tratado de ampliar el nivel de internacionalización de las instituciones superiores, pero aún son escasos los estudios destinados a profundizar en esta temática. Este artículo trata de contribuir al conocimiento de esta cuestión por medio de una revisión de la normativa, las estadísticas oficiales y las publicaciones existentes sobre el proceso de internacionalización de la educación superior en el país. El repaso a la situación actual de dicho proceso permite detectar algunos éxitos conseguidos durante los últimos años, pero pone también de manifiesto la existencia de problemas, por lo que cabe plantear algunas líneas de reflexión que pueden proponerse para el desarrollo futuro de las políticas de este ámbito. PALABRAS CLAVE:Internacionalización, Educación superior, China. ABSTRACTIn the context of economic globalization, the internationalization of higher education appears as a tendency that is modifying the educational reform agendas at this level in all countries. In the case of China, the policies adopted in recent years have been * Universidad Complutense de Madrid (España).