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Large size cerium (Ce3+)‐doped potassium chloride single crystal is grown by the resistance heating Czochralski method and characterized structurally, mechanically, and optically by carrying out X‐ray diffraction (XRD), micro‐hardness, photoluminescence (PL), PL excitation (PLE), thermo‐luminescence (TL), and decay time measurements. XRD measurements reveal the incorporation of Ce atoms into the KCl host lattice. Microhardness measurements indicate an improvement in the hardness due to Ce3+‐doping and a decrease of hardness with increasing temperature. Two intense PL emission peaks are observed at wavelengths 343 and 367 nm, attributed, respectively, to the 5d→2F5/2 and 5d→2F7/2 transitions of Ce3+. Energy level scheme for the Ce3+ ion in the KCl crystal is proposed through PL and PLE analyses. The observed TL glow curve of KCl:Ce3+ shows a sharp peak located at about 244 °C. XRD, PL, and TL studies confirm the trivalent state of Ce3+ ion in the KCl host lattice. The luminescence decay time of KCl:Ce3+ crystal is found to be 35.14 ± 0.17 ns. The present study indicates that the KCl:Ce3+ crystal grown exhibiting suitable PL and TL emissions is expected to be a potential material for radiation dosimetry and scintillation applications. [ABSTRACT FROM AUTHOR]

Inducible regulatory T cells (iTregs) are an important subset of Tregs and play a role in the maintenance of peripheral tolerance, and the occurrence of a number of diseases, including tumors and autoimmune diseases. However, the instability of iTregs is a major obstacle for their potential application in clinical trials. The underlying mechanism of iTreg instability remains largely unknown. In the present study, the expression level of microRNA (miRNA/miR)-30a in murine iTregs was evaluated using reverse transcription-quantitative PCR. miR-30a mimics and a miR-negative control (NC) were transiently transfected into iTregs using Nucleofector technology. The effects of miR-30a on the suppressive function of murine iTregs in vitro and in vivo were investigated using MTT, adoptive cell transfer (ACT) and flow cytometry assays, as well as a murine model of lung cancer. In the present study, it was identified that the expression level of miR-30a was lower in murine iTregs in vitro compared with natural (n)Tregs. Furthermore, compared with miR-NC, miR-30a mimics impaired the suppressive function of murine iTregs on murine CD4+ T cell proliferation in vitro, which was accompanied by the altered expression of cytotoxic T lymphocyte-associated antigen 4 and glucocorticoid induced tumor necrosis factor receptor, as well as transforming growth factor-β and interleukin-10. It was also observed that, compared with miR-NC, miR-30a mimics abrogated the suppressive effects of murine iTregs on murine CD8+ T cell function in vivo, producing an effective antitumor effect in mice bearing 3LL lung cancer cells in the ACT assay. From a mechanistic point, the expression level of suppressor of cytokine signaling 1, a putative target of miR-30a, was elevated, altering the activation of the Akt and STAT1 pathway in the miR-30a mimic transfected group compared with the miR-NC group, reducing the suppressive function of murine iTregs. The present study identified a role for miR-30a in the instability of iTregs and provided a novel insight into the development of therapeutic strategies for promoting T-cell immunity via the regulation of iTreg instability by targeting specific miRNAs. [ABSTRACT FROM AUTHOR]

Our recent evidence showed that prior expansion of CCR6+ Foxp3+ regulatory T cells (Tregs) was important for their dominant enrichment in tumor tissue, which was closely related to poor prognosis of breast cancer patients. However, the underlying regulation mechanism of expansion of CCR6+ Tregs in situ remains largely unknown. In this study, we reported that miR-21 was highly expressed in CCR6+ Tregs in tumor tissues from a murine breast cancer model. And silencing of miR-21 could significantly reduce the proliferation of CCR6+ Tregs in vitro. Adoptive cell-transfer assay further showed that silencing of miR-21 could alter the enrichment of CCR6+ Tregs in the tumor mass and endow effectively antitumor effect of CD8+ T cells using a murine breast cancer model. Mechanistic evidence showed that silencing of miR-21 enhanced the expression of its target phosphatase and tensin homolog deleted on chromosome ten (PTEN) and subsequently altered the activation of Akt pathway, which was ultimately responsible for reduced proliferation activity of CCR6+ Tregs. Finally, we further revealed that miR-21 was also highly expressed on CCR6+ Tregs in clinical breast cancer patients. Therefore, miR-21 can act as a fine tuner in the regulation of PTEN/Akt pathway transduction in the expansion of CCR6+ Tregs in tumor sites and provided a novel insight into the development of therapeutic strategies for promoting T-cell immunity by regulating distinct subset of Tregs through targeting specific miRNAs. [ABSTRACT FROM AUTHOR]

Recent evidence showed that limited activation of PI3K/Akt pathway was critical for induction and function sustainment of CD4+Foxp3+ regulatory T cells (Tregs). However, the underlying mechanism remains largely unknown. In this study, we reported that miR-126 was expressed in mouse and human Tregs. Further study showed that silencing of miR-126 using miR-126 antisense oligonucleotides ( ASO) could significantly reduce the induction of Tregs in vitro. Furthermore, miR-126 silencing could obviously reduce the expression of Foxp3 on Tregs, which was accompanied by decreased expression of CTLA-4 and GITR, as well as IL-10 and TGF-β, and impair its suppressive function. Mechanistic evidence showed that silencing of miR-126 enhanced the expression of its target p85β and subsequently altered the activation of PI3K/Akt pathway, which was ultimately responsible for reduced induction and suppressive function of Tregs. Finally, we further revealed that miR-126 silencing could impair the suppressive function of Tregs in vivo and endow effectively antitumour effect of CD8+T cells in adoptive cell transfer assay using a murine breast cancer model. Therefore, our study showed that miR-126 could act as fine-tuner in regulation of PI3K-Akt pathway transduction in the induction and sustained suppressive function of Tregs and provided a novel insight into the development of therapeutic strategies for promoting T-cell immunity by regulating Tregs through targeting specific mi RNAs. [ABSTRACT FROM AUTHOR]

Objective: To detect the expression of miR-126 in different tissues and organs and the change of peripheral blood glucose in microRNA-126 knock down (miR-126 KD) mouse, and to explore the pathological significance., Methods: Total RNAs were isolated from twelve kinds of tissues and organs in wild-type mouse (WT) and miR-126 KD mouse respectively. Th en, the expression level of miR-126 was detected by real-time PCR assay. Th e levels of peripheral blood glucose and body weight of miR-126 KD mice were measured. Th e pathologic changes of pancreas and lung tissue were observed by HE staining., Results: Compared with the WT mice, the relative expression of miR-126 in spleen, liver, muscle and lung from the miR-126 KD mice were dramatically decreased respectively (P<0.05). The level of peripheral blood glucose in the miR-126 KD mouse increased significantly at seven week and sixteen week after the birth (P<0.05). HE staining showed that the pathological structure of pancreas and liver were abnormal. The body weight of miR-126 KD mice was increased obviously from thirteen week after birth (P<0.05)., Conclusion: Peripheral blood glucose levels in the miR-126 KD mouse were dramatically elevated, which might be related to the pathological changes in the structure of pancreas and liver. These results suggest that miR-126 may play an important role in the metabolism of blood glucose and the development of type 2 diabetes mellitus.

Backgroud. CCR6(+) CD4(+) regulatory T cells (CCR6(+) Tregs), a distinct Tregs subset, played an important role in various immune diseases. Recent evidence showed that microRNAs (miRNAs) are vital regulators in the function of immune cells. However, the potential role of miRNAs in the function of CCR6(+) Tregs remains largely unknown. In this study, we detected the expression profile of miRNAs in CCR6(+) Tregs. Materials and Methods. The expression profile of miRNAs as well as genes in CCR6(+) Tregs or CCR6(-) Tregs from Balb/c mice were detected by microarray. The signaling pathways were analyzed using the Keggs pathway library. Results. We found that there were 58 miRNAs significantly upregulated and 62 downregulated up to 2 fold in CCR6(+) Tregs compared with CCR6(-) Tregs. Moreover, 1,391 genes were observed with 3 fold change and 20 signaling pathways were enriched using the Keggs pathway library. Conclusion. The present data showed CCR6(+) Tregs expressed specific miRNAs pattern, which provides insight into the role of miRNAs in the biological function of distinct Tregs subsets.

Objective: To investigate the effect of microRNA-7 (miR-7) over-expression on the growth of human lung cancer cells in vivo and in vitro and explore its possible mechanism., Methods: The eukaryotic expression vector of pcDNA3.1 encoding miR-7 (p-miR-7) was transiently transfected into human lung cancer 95D cells in vitro. The proliferation of cells was detected by MTT assay and colony formation assay. Moreover, the expressions of nuclear antigen Ki-67 and CGG binding protein 1 (CGGBP1) were detected by immunofluorescence assay. Human lung cancer model in nude mice was established. Next, p-miR-7 vector was directly injected into local tumor tissue. Then, tumor size was measured and the survival time of mice was observed. The expression level of miR-7 in the tumor tissue was determined by real-time PCR. Finally, the expressions of Ki-67 and CGGBP1 were detected by immunohistochemistry., Results: Over-expression of miR-7 could significantly inhibit the growth of 95D cells in vitro (P<0.05), accompanied by the remarkably reduced expressions of Ki-67 and CGGBP1 (P<0.05). Moreover, compared with those in control group, the expression level of miR-7 increased significantly in p-miR-7 injected group (P<0.05). Meanwhile, the growth of tumors in injected group was slower than in the control group. Consistently, the survival time of mice was dramatically prolonged in p-miR-7 injected group (P<0.05). The expression levels of Ki-67 and CGGBP1 also remarkably decreased in tumor tissue (P<0.05)., Conclusion: Over-expression of miR-7 could significantly inhibit the growth of human lung cancer cells in vivo and in vitro, which might be related to the down-regulated expression of tumor growth-associated protein CGGBP1.