Drug resistance remains a major clinical obstacle to successful treatment in ovarian cancer patients, and the evidence of microRNAs involvement in drug resistance has been emerging recently. In this report, we investigated the role of let-7e in the development of cisplatin-resistant ovarian cancer. On the cellular level, let-7e expression was significantly reduced in cisplatin-resistant human epithelial ovarian cancer (EOC) cell line A2780/CP compared with parental A2780 cell and decreased in a concentration-dependent manner in A2780, SKOV3 and ES2 cells treated with cisplatin. Overexpression of let-7e by transfection of agomir could resensitize A2780/CP and reduce the expression of cisplatin-resistant-related proteins enhancer of zeste 2 (EZH2) and cyclin D1 (CCND1), whereas let-7e inhibitors increased resistance to cisplatin in parental A2780 cells. Quantitative methylation-specific PCR analysis showed hypermethylation of the CpG island adjacent to let-7e in A2780/CP cells, and demethylation treatment with 5-aza-CdR or transfection of pYr-let-7e-shRNA plasmid containing unmethylated let-7e DNA sequence could restore let-7e expression and partly reduce the chemoresistance. In addition, cisplatin combined with let-7e agomirs inhibited the growth of A2780/CP xenograft more effectively than cisplatin alone. Diminished expression of EZH2 and CCND1 and higher cisplatin concentrations in tumor tissue of mice subjected to administration of let-7e agomirs in addition to cisplatin were revealed by immunohistochemistry and atomic absorption spectroscopy, respectively. Taken together, our findings suggest that let-7e may act as a promising therapeutic target for improvement of the sensibility to cisplatin in EOC.
A study was conducted to investigate the effect of different monochromatic lights on growth performance and hematological response of growing broiler chickens. A total of 360 one-day-old broiler chicks were randomly divided into 6 lighting treatments, which were replicated 6 times with 10 chicks in each replicate. Six light treatments include incandescent bulbs (as a control) and light-emitting diode white light, blue light, red light, green light, and yellow light (YL). The birds were provided with similar nutritional specifications and environmental management facilities, except for the lights throughout the experimental period. Growth performance was evaluated in terms of BW, BW gain, feed intake, and feed conversion ratio at weekly intervals. At the end of 5 wk, 2 birds from each replicate were randomly selected for blood collection to determine hematological response. The BW and feed intake was numerically higher in YL at 5 wk of age. But interestingly, this did not result in improved feed conversion ratio in YL; nevertheless, numerical values were lower in YL at 5 wk (P > 0.05). Red blood cells, blood platelet count, and percent hematocrit were numerically higher under YL, whereas white blood cell counts and percent hemoglobin remained unaffected due to light treatments. It was concluded that monochromatic light is a potential light source that might provide a beneficial effect on growth performance but is inconclusive for hematological measures of broilers.
Cardamonin has been demonstrated to have an inhibitory effect in many cancers, but its underlying mechanism remains elusive. Here, we studied, for the first time, the mechanism of cardamonin-induced nasopharyngeal carcinoma cell death both in vitro and in vivo. In our study, we showed that cardamonin inhibited cancer cell growth by inducing G2/M phase cell cycle arrest and apoptosis via accumulation of ROS. NF-κB activation was involved in breaking cellular redox homeostasis. Therefore, our results provided new insight into the mechanism of the antitumor effect of cardamonin, supporting cardamonin as a prospective therapeutic drug in nasopharyngeal carcinoma by modulating intracellular redox balance.
The role of monochromatic lights was investigated on meat quality in 1-d-old straight-run broiler chicks (n = 360), divided into 6 light sources with 6 replicates having 10 chicks in each replicate. Six light sources were described as incandescent bulbs (IBL, as a control) and light-emitting diode (LED) light colors as white light (WL), blue light, red light (RL), green light, and yellow light. Among LED groups, the RL increased the concentration of monounsaturated fatty acids (P < 0.001), saturated fatty acids (P < 0.001), and the saturated:polyunsaturated fatty acid ratio (P < 0.001), but reduced the concentration of polyunsaturated fatty acid, n-3 fatty acid, and n-6 fatty acid. The IBL increased the n-3 and sulfur-containing amino acids but reduced the n-6:n-3 nonessential amino acids. The WL improved the concentration of most of the essential amino acids (P < 0.01) and nonessential amino acids (P < 0.01) of breast meat. It can be extracted that the light produced by LED responded similar to the IBL light in influencing nutrient contents of meat. Moreover, LED is not decisive in improving fatty acid composition of meat. However, the role of IBL in reducing n-6:n-3 ratio and enhancing n-3 cannot be neglected. Among LED, WL is helpful in improving essential and nonessential amino acid contents of broiler meat.
Existing evidence has shown that circulating Epstein-Barr virus (EBV)-miR-BART13-3p is highly expressed in plasma of nasopharyngeal carcinoma (NPC) patients, especially among patients with advanced diseases. However, the exact role that EBV-miR-BART13-3p plays in the development of NPC remains poorly understood. Here we show that up-regulated expression of EBV-miR-BART13-3p leads to increased capacity in migration and invasion of NPC cells in vitro and causes tumor metastasis in vivo. Furthermore, we find that EBV-miR-BART13-3p directly targets ABI2, known as a tumor suppressor and a cell migration inhibitor, drives epithelial-mesenchymal transition (EMT) by activating c-JUN/SLUG signaling pathway. Silencing ABI2 shows similar effects to overexpression of EBV-miR-BART13-3p, whereas reconstitution of ABI2 resulted in a phenotypic reversion, highlighting the role of ABI2 in EBV-miR-BART13-3p-driven metastasis in NPC. Besides, expression levels of ABI2 in NPC tissue samples correlate with N stages of NPC patients. Taken together, these results suggest a novel mechanism by which ABI2 downregulation by EBV-miR-BART13-3p promotes EMT and metastasis of NPC via upregulating c-JUN/SLUG signaling pathway.
The present experiment was conducted to evaluate the impact of various levels and forms of α-lipoic acid (ALA) on blood biochemistry, immune and stress response, and antibody titers in broiler chickens. The four levels (7.5, 15, 75, and 150 ppm) and 2 sources (powder, P-ALA and encapsulated, E-ALA) of ALA along with negative (C-) and positive control (C+; contains antibiotics) diets consisted of 10 dietary treatments, and these treatments were allocated to 1,200 1-d-old chicks and were replicated 12 times with 10 birds per replicate. Among the blood biochemistry parameters, creatinine levels were almost 3 times lower in E-ALA-supplemented diets compared to the C- diet (0.09 vs. 0.25 mg/dL; P<0.0001). Neither level nor source of ALA affected blood urea nitrogen (BUN), total protein (TP), albumin, globulin, or albumin to globulin ratio (AGR). The supplemented diets decreased serum levels of the liver enzymes aspartate-aminotransferase (AST; P<0.006) and alanine-aminotransferase (ALT; P<0.0003). The Newcastle disease virus (NDV) antibody response in supplemented groups was poor at day zero (P<0.0001) but increased by d 14 (P<0.03). Birds did not respond to infectious bronchitis virus (IBV) vaccination at any observed stage (P>0.05). The concentration of cortisol was reduced in chickens fed ALA-supplemented diets as compared to the C- diet (P<0.001). Results suggest that ALA-supplemented diets ameliorated blood biochemistry profiles and immune responses and reduced stress in broiler chickens. The encapsulated form of ALA was more effective than the powder form.
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