Chemoresistance in gastric cancer is attributed to the overexpression of excision repair cross-complementing 1 (ERCC1) caused by microRNA-122 dysregulation.

MicroRNAs are deemed as key regulators of gene expression. In particular, the elevated expression of excision repair cross-complementing 1 (ERCC1) significantly reduced the effectiveness of gastric cancer treatment by cisplatin (CDDP)-based therapies. In this paper, qRT-PCR and western blot were adopted to measure miR-122 and ERCC1 messenger RNA (mRNA) expression in all samples. Luciferase assay was carried out to verify the role of ERCC1 as a target of miR-122. The CCK-8 assay was carried out to study the effect of ERCC1 and miR-122 on cell survival and apoptosis. The results demonstrated that miR-122 expression was reduced in cisplatin-resistant gastric cancer. Using bioinformatic analysis, miR-122 was shown to target the 3'-UTR of human ERCC1. A dual-luciferase assay demonstrated that miR-122 downregulated ERCC1 expression, while the mutations in ERCC1 3'-UTR abolished its interaction with miR-122. Transfection of miR-122 mimics decreased the levels of ERCC1 mRNA and protein expression, while the transfection of miR-122 inhibitors increased the levels of both ERCC1 mRNA and protein expression. Furthermore, we found that overexpressed miR-122 promoted the proliferation of MKN74 cells and reduced their apoptotic by targeting ERCC1. In addition, the levels of miR-122 and ERCC1 were negatively correlated in gastric cancer samples. In summary, the reduced miR-122 expression may play an essential role in the induction of cisplatin-resistance by increasing ERCC1 expression.

Licoricidin improves neurological dysfunction after traumatic brain injury in mice via regulating FoxO3/Wnt/ß-catenin pathway.

Traumatic brain injury (TBI) is a major cause of death and disability around the world with no effective treatments currently. The present study was aimed to investigate the neuroprotective effect of licoricidin, one of the major components of licorice extract, on TBI mice and further explore the underlying mechanism. Male C57BL/6 mice were modeled by a modified weight-drop method to mimic TBI. All animals received treatment 30 min after TBI. The modified Neurological Severity Score (NSS) tests were performed at 2 h and 1-3 days after TBI. The brain edema was analyzed by dry-wet weight method. The malonaldehyde (MDA) levels and the activities of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and catalase (CAT) were determined by Elisa. Apoptotic neurons were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) immunofluorescence and the expression of apoptotic proteins were measured by western blot. Activation of the FoxO3/Wnt/ß-catenin was evaluated by western blot. The results showed that treatment with licoricidin could significantly decline the NSS scores and reduce the brain edema, hence promote the recovery of neurological function in TBI mice. It also elevated the phosphorylation of p66shc, brought down the levels of MDA, as well as antagonized the decrement in activities of GSH-PX, SOD and CAT induced by TBI. Moreover, licoricidin decreased the TUNEL positive neurons, downregulated the expression of Cyt-C, cleaved-Caspase-3, cleaved-Caspase-9 and Bax and upregulated the Bcl-2, attenuated cellular apoptosis. Licoricidin decreased the expression of FoxO3 and increased the Wnt/ß-catenin in TBI mice. In conclusion, Licoricidin exerted neuroprotective effect on TBI model and the effect was possibly due to its antioxidative effect and antiapoptotic effect via regulating the FoxO3/Wnt/ß-catenin pathway. Licoricidin may be a candidate drug for TBI therapy.

Day-1 PELOD-2 and day-1 "quick" PELOD-2 scores in children with sepsis in the PICU.

OBJECTIVES: This study aimed to evaluate the predictive validity of the day-1 PELOD-2 and day-1 "quick" PELOD-2 (qPELOD-2) scores for in-hospital mortality in children with sepsis in a pediatric intensive care unit (PICU) of a developing country. METHODS: The data of 516 children diagnosed as sepsis were retrospectively analyzed. The children were divided into survival group and non-survival group, according to the clinical outcome 28 days after admission. Day-1 PELOD-2, day-1 qPELOD-2, pediatric SOFA (pSOFA), and P-MODS were collected and scored. Receiver operating characteristic (ROC) curves were plotted, and the efficiency of the day-1 PELOD-2, day-1 qPELOD-2 score, pSOFA, and P-MODS for predicting death were evaluated by the area under the ROC curve (AUC). RESULTS: The day-1 PELOD-2 score, day-1 qPELOD-2 score, pSOFA, and P-MODS in the non-survivor group were significantly higher than those in the survivor group. ROC curve analysis showed that the AUCs of the day-1 PELOD-2 score, day-1 qPELOD-2 score, pSOFA, and P-MODS for predicting the prognosis of children with sepsis in the PICU were 0.916, 0.802, 0.937, and 0.761, respectively (all p < 0.05). CONCLUSIONS: Both the day-1 PELOD-2 score and day-1 qPELOD-2 score were effective and able to assess the prognosis of children with sepsis in a PICU of a developing country. Additionally, the day-1 PELOD-2 score was superior to the day-1 qPELOD-2 score. Further studies are needed to verify the usefulness of the day-1 qPELOD-2 score, particularly outside of the PICU.

Sign inversions of circularly polarized luminescence for helical compounds by chemically fine-tuning operations.

Sign inversions of circularly polarized luminescence (CPL) for the hydro[5]helicene and [5]helicene derivatives were discovered and studied experimentally and theoretically. The inverted CPL signs from the hydro[5]helicene to [5]helicene derivatives were realized by one-step oxidation. The introduction of triphenylamine (TPA) subunits into the helical skeletons also led to the sign inversion of CPL only when there existed an enhanced intramolecular charge-transfer state with a small enough Egap.

Inhibitory effects of petasin on human colon carcinoma cells mediated by inactivation of Akt/mTOR pathway.

BACKGROUND: Colorectal cancer is the third most common cancer worldwide and still lack of effective therapy so far. Petasin, a natural product found in plants of the genus Petasites, has been reported to possess anticancer activity. The present study aimed to investigate the anticolon cancer activity of petasin both in vitro and in vivo. The molecular mechanism of petasin was also further explored. METHODS: Caco-2, LoVo, SW-620, and HT-29 cell lines were used to detect the inhibitory effect of petasin on colon cancer proliferation. Cell viability was determined using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis was analyzed by flow cytometry. Hoechst 33258 staining was used to visualize morphological changes. Cell migration was assessed using a wound-healing migration assay, and cell invasion was investigated using Transwell chambers. Western blotting assays were employed to evaluate the expression levels of proteins in the protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling pathway. Finally, in vivo activity of petasin was evaluated using the SW-620 subcutaneous tumor model established in Balb/c nude mice. Twelve rats were randomly divided into control group and 10 mg/kg petasin group. The tumor volume was calculated every 7 days for 28 days. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was performed to assess the apoptotic effect of petasin. Differences between two groups were assessed by analysis of independent-sample t tests. RESULTS: Petasin significantly inhibited the proliferation of human colon carcinoma cell lines, induced apoptosis, and suppressed migration and invasion in SW-620 cells. Western blotting results showed that petasin decreased the phosphorylation of Akt (1.01 ±â€Š0.16 vs. 0.74 ±â€Š0.06, P = 0.042), mTOR (0.71 ±â€Š0.12 vs. 0.32 ±â€Š0.11, P = 0.013), and P70S6K (1.23 ±â€Š0.21 vs. 0.85 ±â€Š0.14, P = 0.008), elevated the expression of caspase-3 (0.41 ±â€Š0.09 vs. 0.74 ±â€Š0.12, P = 0.018) and caspase-9 (1.10 ±â€Š0.27 vs. 1.98 ±â€Š0.22, P = 0.009), decreased the Bcl-2 protein (2.75 ±â€Š0.47 vs. 1.51 ±â€Š0.36, P = 0.008), downregulated the expression of matrix metalloproteinase (MMP)-3 (1.51 ±â€Š0.31 vs. 0.82 ±â€Š0.11, P = 0.021) and MMP-9 (1.56 ±â€Š0.32 vs. 0.94 ±â€Š0.15, P = 0.039) in SW-620 cell. In vivo, 10 mg/kg petasin inhibited tumor growth in Balb/c nude mice (924.18 ±â€Š101.23 vs. 577.67 ±â€Š75.12 mm at day 28, P = 0.001) and induced apoptosis (3.6 ±â€Š0.7% vs. 36.0 ±â€Š4.9%, P = 0.001) in tumor tissues. CONCLUSIONS: Petasin inhibits the proliferation of colon cancer SW-620 cells via inactivating the Akt/mTOR pathway. Our findings suggest petasin as a potential candidate for colon cancer therapy.

Intense blue circularly polarized luminescence from helical aromatic esters.

A new class of chiral organic molecules was synthesized with CPL properties based on helical aromatic esters. The molecules not only show blue fluorescence with high quantum yields in solution and films, but also exhibit intense CPL with large glum.

Day-1 PELOD-2 and day-1 quick PELOD-2 scores in children with sepsis in the PICU / Desempenhos dos escores PELOD-2 no dia 1 e quick PELOD-2 no dia 1 em crianças com sepse na UTIP

Abstract Objectives: This study aimed to evaluate the predictive validity of the day-1 PELOD-2 and day-1 "quick" PELOD-2 (qPELOD-2) scores for in-hospital mortality in children with sepsis in a pediatric intensive care unit (PICU) of a developing country. Methods: The data of 516 children diagnosed as sepsis were retrospectively analyzed. The children were divided into survival group and non-survival group, according to the clinical outcome 28 days after admission. Day-1 PELOD-2, day-1 qPELOD-2, pediatric SOFA (pSOFA), and P-MODS were collected and scored. Receiver operating characteristic (ROC) curves were plotted, and the efficiency of the day-1 PELOD-2, day-1 qPELOD-2 score, pSOFA, and P-MODS for predicting death were evaluated by the area under the ROC curve (AUC). Results: The day-1 PELOD-2 score, day-1 qPELOD-2 score, pSOFA, and P-MODS in the non-survivor group were significantly higher than those in the survivor group. ROC curve analysis showed that the AUCs of the day-1 PELOD-2 score, day-1 qPELOD-2 score, pSOFA, and P-MODS for predicting the prognosis of children with sepsis in the PICU were 0.916, 0.802, 0.937, and 0.761, respectively (all p < 0.05). Conclusions: Both the day-1 PELOD-2 score and day-1 qPELOD-2 score were effective and able to assess the prognosis of children with sepsis in a PICU of a developing country. Additionally, the day-1 PELOD-2 score was superior to the day-1 qPELOD-2 score. Further studies are needed to verify the usefulness of the day-1 qPELOD-2 score, particularly outside of the PICU.

Resumo Objetivos: A finalidade de nosso estudo foi avaliar a validade preditiva dos escores PELOD-2 no dia 1 e "quick" PELOD-2 no dia 1 com relação à mortalidade hospitalar em crianças com sepse em uma UTIP de um país em desenvolvimento. Métodos: Foram analisados retrospectivamente os dados de 516 crianças diagnosticadas com sepse. As crianças foram divididas em grupo sobrevida e grupo não sobrevida de acordo com o desfecho clínico de 28 dias após internação. Foram coletadas e pontuadas as variáveis PELOD-2 no dia 1, qPELOD-2 no dia 1, pediatric Sequential Organ Failure Assessment (pSOFA) e Pediatric Multiple Organ Dysfunction Score (P-MODS). A curva da característica de operação do receptor (ROC) foi plotada e a eficiência preditiva do PELOD-2 no dia 1, o escore qPELOD-2 no dia 1, pSOFA, P-MODS com relação a óbito foram avaliados pela área abaixo da curva (AUC) da curva ROC. Resultados: O escore PELOD-2 no dia 1, escore qPELOD-2 no dia 1, pSOFA e P-MODS no grupo não sobrevida foram significativamente maiores do que os no grupo sobrevida. A análise preditiva da curva ROC mostrou que as AUCs do escore PELOD-2 no dia 1, escore qPELOD-2 no dia 1, pSOFA e P-MODS com relação ao prognóstico de crianças com sepse na UTIP foi 0,916, 0,802, 0,937 e 0,761, respectivamente (todas p < 0,05). Conclusões: Tanto o escore PELOD-2 no dia 1 e o escore qPELOD-2 no dia 1 foram válidos e conseguiram avaliar o prognóstico de crianças com sepse em uma UTIP de um país em desenvolvimento. Além disso, o escore PELOD-2 no dia 1 foi superior ao escore qPELOD-2 no dia 1. São necessários estudos adicionais para verificar a utilidade do escore qPELOD-2 no dia 1, principalmente fora da UTIP.

Helicobacter pylori enhances CIP2A expression and cell proliferation via JNK2/ATF2 signaling in human gastric cancer cells.

Helicobacter pylori (H. pylori) infection plays an important role in the development of gastric carcinomas. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a novel human oncoprotein that functions as an important regulator of cell growth and malignant transformation. In the present study, we aimed to investigate the potential mechanisms by which H. pylori upregulates the expression of CIP2A and the functional impact of H. pylori-induced CIP2A in gastric cancer cells. We demonstrated that infection of MKN-45 cells with H. pylori led to a marked increase in the expression of CIP2A at the mRNA and protein levels. H. pylori-induced CIP2A was associated with increased cell proliferation. In addition, H. pylori was found to activate the JNK2 pathway. Importantly, both H. pylori-induced CIP2A production and cell proliferation were partially reversed by inhibition of JNK2 signaling. Similarly, the blockade of H. pylori-induced CIP2A expression by siRNA against CIP2A also inhibited cell proliferation. Thus, H. pylori appears to stimulate the expression of CIP2A and proliferation of gastric cancer cells via JNK2 signaling. These findings suggest that H. pylori-induced upregulation of CIP2A contributes to the development and progression of gastric cancer. Further in vivo studies are warranted to explore the biological role of CIP2A and its interaction with JNK2 signaling in gastric cancer.

Notch2 regulates matrix metallopeptidase 9 via PI3K/AKT signaling in human gastric carcinoma cell MKN-45.

AIM: To clarify the role of activated Notch2 in the invasiveness of gastric cancer. METHODS: To investigate the invasiveness of silencing Notch2 gene expression, we established a Notch2 small interfering RNA (siRNA) transfected cell line using the MKN-45 gastric cancer cell line. After the successful transfection confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, migration and invasion assays were employed to evaluate the aggressiveness of the gastric cancer. RT-PCR and Western blottings were employed to confirm the down-regulation of Notch2 and to evaluate the expression of epithelial mesenchymal transition-related gene matrix metallopeptidase 9 (MMP9), Akt, p-Akt. To confirm the relationship between PI3K-Akt and MMP9, the PI3K inhibitor LY294002 was used to treat MKN-45 cells. RESULTS: Notch2 expression was dramatically decreased after Notch2 siRNA transfection (100.00% ± 9.74% vs 11.61% ± 3.85%, P < 0.01 by qRT-PCR). There was also a marked reduction of Notch target gene Hes1 (100.00% ± 4.74% vs 61.61% ± 3.58%, P < 0.05) at the mRNA, indicating an inhibition of Notch signaling. Inhibition of Notch signaling was also confirmed by the marked reduction of Notch2 intracellular domain at the protein levels (100.00% ± 9.74% vs 65.61% ± 7.58%, P < 0.05). Down-regulation of Notch2 by siRNA enhanced tumor cell invasion (100.00% ± 21.64% vs 162.22% ± 16.84%, P < 0.05) and expression of MMP9 (1.56 fold, P < 0.05), and activated the pro-MMP9 protein to its active form (1.48 fold, P < 0.05). There was no significant difference in the protein levels of Akt between the two groups (100.00% ± 10.87% vs 96.61% ± 7.33%, P > 0.05), while down-regulation of Notch2 elevated p-Akt expression (100.00% ± 9.87% vs 154.61% ± 13.10%, P < 0.05). Furthermore, p-Akt and MMP9 was down-regulated in response to the inhibitor LY294002 (p-Akt 100.00% ± 8.87% vs 58.27% ± 5.01%, P < 0.05; MMP9 100.00% ± 9.17% vs 50.03% ± 4.88%, P < 0.05). CONCLUSION: Notch2 may negatively regulate cell invasion by inhibiting the PI3K-Akt signaling pathway in gastric cancer.