Theoretical and experimental investigation of Al3+ ion-suppressed phase-separation structures in rare-earth-doped high-phosphorus silica glasses.

Rare-earth-doped silica-based composite glasses (Re-SCGs) are widely used as high-quality laser gain media in defense, aerospace, energy, power, and medical applications. The variable regional chemical environments of Re-SCGs can induce new photoluminescence properties of rare-earth ions but can cause the selective aggregation of rare-earth ions, limiting the application of Re-SCGs in the field of high-power lasers. Here, topological engineering is proposed to adjust the degree of cross-linking of phase-separation network chains in Re-SCGs. A combination of experimental and theoretical characterization techniques suggested that the selective aggregation of rare-earth ions originates from the formation of phase-separated structures in glasses. The decomposition of nanoscale phase separation structures to the sub-nanometer scale, enabled by incorporating Al3+ ions, not only maintains the high luminescence efficiency of rare earth ions but also increases light transmittance and reduces light scattering. Furthermore, our investigation encompassed the exploration of the inhibitory mechanism of Al3+ ions on phase-separation structures, as well as their influence on the spectral characteristics of Re-SCGs. This work provides a new design concept for composite glass materials doped with rare-earth ions and could broaden their application in the field of high-power lasers.

Saikosaponin A Inhibits Growth of Human Bladder Carcinoma T24 and 5637 Cells Both in Vitro and in Vivo.

Saikosaponin A (SSA)-a natural compound extracted from Radix bupleuri-possesses antitumor properties in several types of carcinomas. However, the role of SSA on bladder cancer and the mechanisms remain unclear. In this study, we have described the effect of SSA on human bladder cancer cell lines T24 and 5637 in the context of the regulation of mitochondrial pathways of apoptosis. In vitro, the Cell Counting Kit-8 (CCK-8) assay and cell wound healing assays were used to determine the proliferative effect of SSA treatment. Flow cytometry and Western blotting were performed to evaluate the apoptosis and related mechanisms. To further confirm that apoptosis is mediated through Caspase activation, Hoechst 33258 fluorescence staining assay was done after cells were treated with SSA and caspase inhibitor-Z-VAD-FMK. In vivo, an orthotopic xenograft mice model was adopted to evaluate the effect of SSA. The tumors were analyzed by hematoxylin-eosin (H&E) staining, immunohistochemical analysis, and Western blotting. In vitro, the results with CCK-8 assay showed obvious SSA-induced suppression in cell growth in a dose- and time-dependent manner. Flow cytometry analysis, Hoechst 33258 fluorescence staining assay and the assessment of the changes in the B-cell lymphoma 2 (Bcl-2) family protein expression level revealed that SSA could significantly induce cell apoptosis, which was associated with apoptosis via the mitochondrial pathways. In vivo, the results revealed a reduction in cell proliferation. In conclusion, our data suggest that SSA inhibits the growth of bladder cancer cells by activating the mitochondrial apoptosis pathway and inducing cell apoptosis.

Tectorigenin enhances PDX1 expression and protects pancreatic ß-cells by activating ERK and reducing ER stress.

Pancreas/duodenum homeobox protein 1 (PDX1) is an important transcription factor that regulates islet ß-cell proliferation, differentiation, and function. Reduced expression of PDX1 is thought to contribute to ß-cell loss and dysfunction in diabetes. Thus, promoting PDX1 expression can be an effective strategy to preserve ß-cell mass and function. Previously, we established a PDX1 promoter-dependent luciferase system to screen agents that can promote PDX1 expression. Natural compound tectorigenin (TG) was identified as a promising candidate that could enhance the activity of the promoter for the PDX1 gene. In this study, we first demonstrated that TG could promote the expression of PDX1 in ß-cells via activating extracellular signal-related kinase (ERK), as indicated by increased phosphorylation of ERK; this effect was observed under either normal or glucotoxic/lipotoxic conditions. We then found that TG could suppress induced apoptosis and improved the viability of ß-cells under glucotoxicity and lipotoxicity by activation of ERK and reduction of reactive oxygen species and endoplasmic reticulum (ER) stress. These effects held true in vivo as well: prophylactic or therapeutic use of TG could obviously inhibit ER stress and decrease islet ß-cell apoptosis in the pancreas of mice given a high-fat/high-sucrose diet (HFHSD), thus dramatically maintaining or restoring ß-cell mass and islet size, respectively. Accordingly, both prophylactic and therapeutic use of TG improved HFHSD-impaired glucose metabolism in mice, as evidenced by ameliorating hyperglycemia and glucose intolerance. Taken together, TG, as an agent promoting PDX1 expression exhibits strong protective effects on islet ß-cells both in vitro and in vivo.

20(S)-25-methoxyl-dammarane-3ß, 12ß, 20-triol negatively regulates activation of STAT3 and ERK pathways and exhibits anti-cancer effects in HepG2 cells.

The pro-inflammatory cytokine interleukin 6 (IL-6), via activating its downstream JAK/STAT3 and Ras/ERK signaling pathways, is involved in cell growth, proliferation and anti-apoptotic activities in various malignancies. To screen inhibitors of IL-6 signaling, we constructed a STAT3 and ERK dual-pathway responsive luciferase reporter vector (Co.RE). Among several candidates, the natural compound 20(S)-25-methoxyl-dammarane-3ß, 12ß, 20-triol (25-OCH3-PPD, GS25) was identified to clearly inhibit the luciferase activity of Co.RE. GS25 was confirmed to indeed inhibit activation of both STAT3 and ERK pathways and expression of downstream target genes of IL-6, and to predominantly decrease the viability of HepG2 cells via induction of cell cycle arrest and apoptosis. Interestingly, GS25 showed preferential inhibition of HepG2 cell viability relative to normal liver L02 cells. Further investigation showed that GS25 could not induce apoptosis and block activation of STAT3 and ERK pathways in L02 cells as efficiently as in HepG2 cells, which may result in differential effects of GS25 on malignant and normal liver cells. In addition, GS25 was found to potently suppress the expression of endogenous STAT3 at a higher concentration and dramatically induce p38 phosphorylation in HepG2 cells, which could mediate its anti-cancer effects. Finally, we demonstrated that GS25 also inhibited tumor growth in HepG2 xenograft mice. Taken together, these findings indicate that GS25 elicits its anti-cancer effects on HepG2 cells through multiple mechanisms and has the potential to be used as an inhibitor of IL-6 signaling. Thus, GS25 may be developed as a treatment for hepatocarcinoma with low toxicity on normal liver tissues as well as other inflammation-associated diseases.

Synthesis and antitumor activity of novel 2-substituted indoline imidazolium salt derivatives.

A series of novel 2-substituted indoline imidazolium salt derivatives has been prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the existence of a substituted benzimidazole ring and substitution of the imidazolyl-3-position with a naphthylacyl or 2-naphthylmethyl group were vital for modulating the cytotoxic activity. Compound 25 was found to be the most potent derivative with IC50 values of 0.24-1.18 µM, and exhibited cytotoxic activity selectively against MCF-7, SW480, SMMC-7721 and HL-60 cell lines, while compound 26 showed powerful inhibitory activities selectively against SMMC-7721 and A549 cell lines. Compound 25 can induce G2/M phase cell cycle arrest and apoptosis in SMMC-7721 cells.

Apolipoprotein A5 and apolipoprotein C3 single nucleotide polymorphisms are correlated with an increased risk of coronary heart disease: a case-control and meta-analysis study.

BACKGROUND: Triglycerides (TGs) are proatherogenic lipoproteins involving the risk of coronary heart disease (CHD), while apolipoprotein A5 (APOA5) and apolipoprotein C3 (APOC3) are main lipoproteins composing TG-rich lipoproteins. In this study, we aim to explore the correlation of CHD with APOA5 -1131 T > C and APOC3 -455 T > C single nucleotide polymorphisms (SNPs). METHODS: A sum of 210 CHD patients, hospitalized between Jan. 2013 and Mar. 2015 at China-Japan Union Hospital, Jilin University, were selected as our case group and 223 healthy individuals who had physical examination at same hospital at the same period were selected as control group. The frequency distribution of genotypes of APOA5 -1131 T > C and APOC3 -455 T > C SNPs were measured by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The Stata 12.0 software was utilized for statistical analyses. RESULTS: There was no significant difference on age and sex between case and control group (P > 0.05). History of smoking, drinking, hypertension and diabetes mellitus, body mass index and levels of TG and fasting blood sugar in case group were shown to be higher than control group (P < 0.05), while levels of total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in case group were lower than control group (P < 0.05). Both CC and TC' + CC frequencies of APOA5 -1131 T > C and APOC3 -455 T > C in case group were higher compared to control group (both P < 0.05). Additionally, T allele frequencies of the two SNPs in case group were lower than control group, while C allele in case group has higher frequencies compared to control group (both P < 0.05). The results of meta-analysis under allele and dominant models showed that APOA5 -1131 T > C and APOC3 -455 T > C SNPs are likely to increase the risk of CHD (both P < 0.05). CONCLUSION: APOA5 -1131 T > C and APOC3 -455 T > C SNPs may play potent roles in the development and progression of CHD.

Synthesis and cytotoxic activity of novel 1-((indol-3-yl)methyl)-1H-imidazolium salts.

A series of novel 1-((indol-3-yl)methyl)-1H-imidazolium salts were prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the 5,6-dimethyl-benzimidazole ring, and substitution of the imidazolyl-3-position with a naphthylacyl or 4-bromophenacyl group, were vital for modulating inhibitory activity of cell growth. In particular, 1-((N-Boc-indol-3-yl)methyl)-3-(2-naphthylacyl)-1H-5,6-dimethyl-benzimidazolium bromide was found to be the most potent derivative and more selective against myeloid liver carcinoma (SMMC-7721), lung carcinoma (A549) and breast carcinoma (MCF-7), with IC50 values 1.9-fold, 1.7-fold and 4.8-fold lower than DDP. This compound can induce significant cell apoptosis in SMMC-7721 cells.

Three new compounds from the stem bark of Juglans mandshurica.

Three new compounds, 3,6-dihydroxy-4,5-dimethoxy-1,8-naphalic anhydride (1), 3,4,5,6-tetrahydroxy-1,8-naphalic anhydride (2), and methyl (7E,9E)-6,11-dioxononadeca-7,9-dienoate (3), were isolated from the stem bark of Juglans mandshurica. Their structures were elucidated on the basis of spectroscopic evidence, including 1D and 2D NMR, HR-TOF-MS, and by comparison with the literature data.

To explore the protective effect of gastrodin on PC12 cells against oxidative stress induced by lead acetate based on network pharmacology.

Objective: Screening and predicting potential targets for gastrodin antioxidant stress based on network pharmacology methods, and exploring the effect of gastrodin on lead acetate induced oxidative stress in PC12 cells through cell experiments. Methods: Through the Pharmaper database Predict the target of action of gastrodin. Through OMIM and GeneCards to collect oxidative stress targets from database, and intersect with drug targets to obtain drug disease intersection targets; Construct a PPI network diagram using the STRING database. Perform GO enrichment analysis and KEGG pathway enrichment analysis on intersection targets through the DAVID platform. Lead acetate (PbAc) exposure was used to establish a lead poisoning cell model, and intracellular ROS levels, ALB, AKT1, and Caspase-3 levels were measured. Results: A total of 288 targets of gastrodin action, 638 targets related to oxidative stress, and 62 drug disease intersection targets were obtained, among which core targets such as ALB, AKT1, CASP3 may be closely related to oxidative stress. KEGG pathway analysis showed that gastrodin antioxidant stress mainly involved in lipid, cancer pathway and other signaling pathways. The results of the cell experiment showed that 50 µM is the optimal effective concentration for PbAc induced ROS production in PC12 cells. Gastrodin significantly increased the ROS content of PC12 cells treated with PbAc, Upregulation of ALB expression and downregulation of AKT1 and CASP3 expression. Conclusions: Gastrodin may alleviate PbAc-induced ROS in PC12 cells, indicating potential protective effects against oxidative stress. Further studies are needed to confirm these findings and explore the underlying mechanisms.

Berberine Alleviates Ischemic Brain Injury by Enhancing Autophagic Flux via Facilitation of TFEB Nuclear Translocation.

Berberine has been demonstrated to alleviate cerebral ischemia/reperfusion injury, but its neuroprotective mechanism has yet to be understood. Studies have indicated that ischemic neuronal damage was frequently driven by autophagic/lysosomal dysfunction, which could be restored by boosting transcription factor EB (TFEB) nuclear translocation. Therefore, this study investigated the pharmacological effects of berberine on TFEB-regulated autophagic/lysosomal signaling in neurons after cerebral stroke. A rat model of ischemic stroke and a neuronal ischemia model in HT22 cells were prepared using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD), respectively. Berberine was pre-administered at a dose of 100[Formula: see text]mg/kg/d for three days in rats and 90[Formula: see text][Formula: see text]M in HT22 neurons for 12[Formula: see text]h. 24[Formula: see text]h after MCAO and 2[Formula: see text]h after OGD, the penumbral tissues and OGD neurons were obtained to detect nuclear and cytoplasmic TFEB, and the key proteins in the autophagic/lysosomal pathway were examined using western blot and immunofluorescence, respectively. Meanwhile, neuron survival, infarct volume, and neurological deficits were assessed to evaluate the therapeutic efficacy. The results showed that berberine prominently facilitated TFEB nuclear translocation, as indicated by increased nuclear expression in penumbral neurons as well as in OGD HT22 cells. Consequently, both autophagic activity and lysosomal capacity were simultaneously augmented to alleviate the ischemic injury. However, berberine-conferred neuroprotection could be greatly counteracted by lysosomal inhibitor Bafilomycin A1 (Baf-A1). Meanwhile, autophagy inhibitor 3-Methyladenine (3-MA) also slightly neutralized the pharmacological effect of berberine on ameliorating autophagic/lysosomal dysfunction. Our study suggests that berberine-induced neuroprotection against ischemic stroke is elicited by enhancing autophagic flux via facilitation of TFEB nuclear translocation in neurons.

Elucidating the crosstalk mechanism between IFN-gamma and IL-6 via mathematical modelling.

BACKGROUND: Interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) are multifunctional cytokines that regulate immune responses, cell proliferation, and tumour development and progression, which frequently have functionally opposing roles. The cellular responses to both cytokines are activated via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. During the past 10 years, the crosstalk mechanism between the IFN-gamma and IL-6 pathways has been studied widely and several biological hypotheses have been proposed, but the kinetics and detailed crosstalk mechanism remain unclear. RESULTS: Using established mathematical models and new experimental observations of the crosstalk between the IFN-gamma and IL-6 pathways, we constructed a new crosstalk model that considers three possible crosstalk levels: (1) the competition between STAT1 and STAT3 for common receptor docking sites; (2) the mutual negative regulation between SOCS1 and SOCS3; and (3) the negative regulatory effects of the formation of STAT1/3 heterodimers. A number of simulations were tested to explore the consequences of cross-regulation between the two pathways. The simulation results agreed well with the experimental data, thereby demonstrating the effectiveness and correctness of the model. CONCLUSION: In this study, we developed a crosstalk model of the IFN-gamma and IL-6 pathways to theoretically investigate their cross-regulation mechanism. The simulation experiments showed the importance of the three crosstalk levels between the two pathways. In particular, the unbalanced competition between STAT1 and STAT3 for IFNR and gp130 led to preferential activation of IFN-gamma and IL-6, while at the same time the formation of STAT1/3 heterodimers enhanced preferential signal transduction by sequestering a fraction of the activated STATs. The model provided a good explanation of the experimental observations and provided insights that may inform further research to facilitate a better understanding of the cross-regulation mechanism between the two pathways.

A new compound from liquid fermentation broth of Armillaria mellea and the determination of its absolute configuration.

A new 2,5-diketopiperazine, (R)-2-(2-(furan-2-yl)-oxoethyl)-octahydropyrrolo[1,2-a]pyrazine-1,4-dione, and seven known compounds were isolated from the ethyl acetate extract of liquid fermentation broth of Armillaria mellea. The structures of the isolated compounds were established from NMR and HR-MS data. The absolute configuration of the new compound was established by comparing the experimental electronic circular dichroism (ECD) spectrum with the calculated ECD data.

Juglanthraquinone C, a novel natural compound derived from Juglans mandshurica Maxim, induces S phase arrest and apoptosis in HepG2 cells.

Juglanthraquinone C (1,5-dihydroxy-9,10-anthraquinone-3-carboxylic acid, JC), a naturally occurring anthraquinone isolated from the stem bark of Juglans mandshurica, shows strong cytotoxicity in various human cancer cells in vitro. Here, we first performed a structure-activity relationship study of six anthraquinone compounds (JC, rhein, emodin, aloe-emodin, physcion and chrysophanol) to exploit the relationship between their structural features and activity. The results showed that JC exhibited the strongest cytotoxicity of all compounds evaluated. Next, we used JC to treat several human cancer cell lines and found that JC showed an inhibitory effect on cell viability in dose-dependent (2.5-10 µg/ml JC) and time-dependent (24-48 h) manners. Importantly, the inhibitory effect of JC on HepG2 (human hepatocellular carcinoma) cells was more significant as shown by an IC(50) value of 9 ± 1.4 µg/ml, and 36 ± 1.2 µg/ml in L02 (human normal liver) cells. Further study suggested that JC-induced inhibition HepG2 cell proliferation was associated with S phase arrest, decreased protein expression of proliferation marker Ki67, cyclin A and cyclin-dependent kinase (CDK) 2, and increased expression of cyclin E and CDK inhibitory protein Cip1/p21. In addition, JC significantly triggered apoptosis in HepG2 cells, which was characterized by increased chromatin condensation and DNA fragmentation, activation of caspase-9 and -3, and induction of a higher Bax/Bcl2 ratio. Collectively, our study demonstrated that JC can efficiently inhibit proliferation and induce apoptosis in HepG2 cells.

Testes-specific protease 50 (TSP50) promotes cell proliferation through the activation of the nuclear factor κB (NF-κB) signalling pathway.

TSP50 (testes-specific protease 50) is a testis-specific expression protein, which is expressed abnormally at high levels in breast cancer tissues. This makes it an attractive molecular marker and a potential target for diagnosis and therapy; however, the biological function of TSP50 is still unclear. In the present study, we show that overexpression of TSP50 in CHO (Chinese-hamster ovary) cells markedly increased cell proliferation and colony formation. Mechanistic studies have revealed that TSP50 can enhance the level of TNFα (tumour necrosis factor α)- and PMA-induced NF-κB (nuclear factor κB)-responsive reporter activity, IκB (inhibitor of NF-κB) α degradation and p65 nuclear translocation. In addition, the knockdown of endogenous TSP50 in MDA-MB-231 cells greatly inhibited NF-κB activity. Co-immunoprecipitation studies demonstrated an interaction of TSP50 with the NF-κB-IκBα complex, but not with the IKK (IκB kinase) α/ß-IKKγ complex, which suggested that TSP50, as a novel type of protease, promoted the degradation of IκBα proteins by binding to the NF-κB-IκBα complex. Our results also revealed that TSP50 can enhance the expression of NF-κB target genes involved in cell proliferation. Furthermore, overexpression of a dominant-negative IκB mutant that is resistant to proteasome-mediated degradation significantly reversed TSP50-induced cell proliferation, colony formation and tumour formation in nude mice. Taken together, the results of the present study suggest that TSP50 promotes cell proliferation, at least partially, through activation of the NF-κB signalling pathway.

Virtual screening of specific insulin-like growth factor 1 receptor (IGF1R) inhibitors from the National Cancer Institute (NCI) molecular database.

Insulin-like growth factor 1 receptor (IGF1R) is an attractive drug target for cancer therapy and research on IGF1R inhibitors has had success in clinical trials. A particular challenge in the development of specific IGF1R inhibitors is interference from insulin receptor (IR), which has a nearly identical sequence. A few potent inhibitors that are selective for IGF1R have been discovered experimentally with the aid of computational methods. However, studies on the rapid identification of IGF1R-selective inhibitors using virtual screening and confidence-level inspections of ligands that show different interactions with IGF1R and IR in docking analysis are rare. In this study, we established virtual screening and binding-mode prediction workflows based on benchmark results of IGF1R and several kinase receptors with IGF1R-like structures. We used comprehensive analysis of the known complexes of IGF1R and IR with their binding ligands to screen specific IGF1R inhibitors. Using these workflows, 17 of 139,735 compounds in the NCI (National Cancer Institute) database were identified as potential specific inhibitors of IGF1R. Calculations of the potential of mean force (PMF) with GROMACS were further conducted for three of the identified compounds to assess their binding affinity differences towards IGF1R and IR.

17ßH-Periplogenin, a cardiac aglycone from the root bark of Periploca sepium Bunge.

The title compound {systematic name: 4-[(3S,5S,8R,9S,10R,13R,14S,17S)-3,5,14-trihy-droxy-10,13-dimethyl-hexa-deca-hydro-1H-cyclo-penta-[a]phenanthren-17-yl]furan-2(5H)-one}, C(23)H(34)O(5), was isolated from the roots of Periploca sepium Bunge, a famous Chinese traditional herbal medicine. The three six-membered rings adopt chair conformations, the cyclo-pentane ring displays an approximate envelope conformation (with the C atom bearing the methyl substituent at the flap) and the five-membered lactone ring adopts an essentially planar [maximum deviation of 0.004 (8) Å] conformation. In the crystal, mol-ecules are linked into helical chains along [010] by O-H⋯O hydrogen bonds and weak C-H⋯O inter-actions. Two intra-molecular O-H⋯O hydrogen bonds are also present.

[Infrared multiphoton quantum cutting phenomena of rare earth materials].

Infrared quantum cutting of rare earth ion is an international hot research field. It is significant for the enhancement of solar cell efficiency and for the reduction of solar cell price. The present paper summarizes the research significance of infrared quantum cutting of rare earth ion. Based on the summarization of general principle and loss mechanism of solar cell, the possible method to enhance the solar cell efficiency by infrared quantum cutting is analyzed. Meanwhile, the present paper summarizes the infrared quantum cutting phenomena of Er3+ ion single-doped material. There is intense 4I13/2 --> 4I15/2 infrared quantum cutting luminescence of Er3+ ion when the 2H11/2 energy level is excited. The intense {2H11/2 --> 4I9/2, 4I15/2 --> 4I13/2} cross energy transfer is the main reason for the result in the high quantum cutting efficiency when the 2H11/2 energy level is excited.

[Cooperative downconversion in Tb (0.7 ) Yb (5) : FOV oxyfluoride nanophase vitroceramics].

The present article reports the infrared quantum cutting study of the nanophase oxyfluoride vitroceramics Tb(0.7)Yb (5.0) : FOV. The visible to infrared fluorescence emission spectra, excitation spectra and fluorescence lifetime were measured carefully. The infrared quantum cutting phenomenon {1([5 D4 --> 7 F6](Tb3+), 2([2 F7/2 --> 2 F5/2](Yb3+)} was analyzed based on the above experiments. It was found that the theoretical quantum cutting efficiency is about 121.35% when 5D4 level is excited by 487.0nm light, and about 136.27% when (5D3, 5G6) levels are excited by 378.0 nm light respectively. Meanwhile, it is first time for the present paper to find a cooperative downconversion phenomenon {2([(5D3, 5G6) --> 5D4] (Tb3+), 1([2 F7/2 --> 2 F5/2] (Yb3+)}. That is, the authors found for the first time that the donor Tb3+ ion releases two pieces of energy [(5D3, 5G6) --> 5D4] of small energy photon to produce a middle energy photon [2 F5/2 --> 2 F7/2] of acceptor Yb3+ ion.

[Spectroscopic properties of Pr3+ doped transparent oxyfluoride vitroceramics].

In the present paper, the room-temperature absorption spectrum of Pr+ -doped transparent oxyfluoride vitroceramics (Pr(0.2):FOV) was studied systematically. The optical characterisation of Pr(0.2):FOV was performed. The standard and modified Judd-Ofelt theories were used to determine the J-O intensity parameters. The problems with standard Judd-Ofelt theorie for Pr3+ were discussed. Based on the intensity parameters, some predicted optical parameters, such as the spontaneous radiative transition probabilities, radiative lifetimes, branching ratios and integrated emission cross section were calculated. And the application of Pr:FOV was analyzed. Especially there are large oscillator strength and large integrated emission cross section in the transitions of (3)P0-->(3)H4, (3)P1-->(3)H5 and (3)P0-->(3)H6, (3)P0-->(3)F2. So, they are more worthy of attention. The obtained spectroscopic results show the potential application of the Pr3+ -doped oxyfluoride vitroceramics for solid-state lasers.

Basic FGF downregulates TSP50 expression via the ERK/Sp1 pathway.

Previous studies demonstrated that the expression of testes-specific protease 50 (TSP50) was increased in breast cancer cells and that overexpression of TSP50 can promote tumorigenesis. Thus, it is important to identify the regulatory mechanisms of TSP50 for tumor therapy. In this study, we elucidated the mechanism underlying TSP50 downregulation by basic fibroblast growth factor (bFGF). We used MDA-MB-231 and HEK293T cell lines to address this issue. RT-PCR and promoter activity assays indicated that bFGF downregulates TSP50 expression via transcriptional activation. We next investigated the signaling pathway that mediated the effect of bFGF on TSP50 transcription, and identified that bFGF induced the phosphorylation of ERK and Sp1. An ERK inhibitor suppressed Sp1 phosphorylation and bFGF-reduced TSP50 expression at the mRNA level. In addition, the dominant negative (DN) mutants of ERK and Sp1 both suppressed the reduction of TSP50 by bFGF. Deletion and mutation analyses indicated that the Sp1 site, located within the +237/+239 region of the human TSP50 promoter, is the major responsive element for bFGF. Taken together, our results strongly suggest that bFGF mediates TSP50 downregulation by ERK activation, leading to the phosphorylation of Sp1 in this process.