Although many models have been proposed to accurately predict the response of drugs in cell lines recent years, understanding the genome related to drug response is also the key for completing oncology precision medicine. In this paper, based on the cancer cell line gene expression and the drug response data, we established a reliable and accurate drug response prediction model and found predictor genes for some drugs of interest. To this end, we first performed pre-selection of genes based on the Pearson correlation coefficient and then used ElasticNet regression model for drug response prediction and fine gene selection. To find more reliable set of predictor genes, we performed regression twice for each drug, one with IC50 and the other with area under the curve (AUC) (or activity area). For the 12 drugs we tested, the predictive performance in terms of Pearson correlation coefficient exceeded 0.6 and the highest one was 17-AAG for which Pearson correlation coefficient was 0.811 for IC50 and 0.81 for AUC. We identify common predictor genes for IC50 and AUC, with which the performance was similar to those with genes separately found for IC50 and AUC, but with much smaller number of predictor genes. By using only common predictor genes, the highest performance was AZD6244 (0.8016 for IC50, 0.7945 for AUC) with 321 predictor genes.

Although many models have been proposed to accurately predict the response of drugs in cell lines recent years, understanding the genome related to drug response is also the key for completing oncology precision medicine. In this paper, based on the cancer cell line gene expression and the drug response data, we established a reliable and accurate drug response prediction model and found predictor genes for some drugs of interest. To this end, we first performed pre-selection of genes based on the Pearson correlation coefficient and then used ElasticNet regression model for drug response prediction and fine gene selection. To find more reliable set of predictor genes, we performed regression twice for each drug, one with IC50 and the other with area under the curve (AUC) (or activity area). For the 12 drugs we tested, the predictive performance in terms of Pearson correlation coefficient exceeded 0.6 and the highest one was 17-AAG for which Pearson correlation coefficient was 0.811 for IC50 and 0.81 for AUC. We identify common predictor genes for IC50 and AUC, with which the performance was similar to those with genes separately found for IC50 and AUC, but with much smaller number of predictor genes. By using only common predictor genes, the highest performance was AZD6244 (0.8016 for IC50, 0.7945 for AUC) with 321 predictor genes.

A total of 535 4th∼6th grade students in the Gyeonggi area were surveyed in an effort to increase vegetable preference and intake. They were divided into 3 groups according to the frequency of salad consumption (High-frequency group, HF, more than once a week G; Intermediate-frequency, IFG, 1∼3 times/month;Low-frequency group, LFG, less than once a month). The proportion of subjects who preferred salad over other vegetable dishes was much lower in the LFG than in the other groups. Compared to the HFG, more students in the LFG gave ‘dressing’ as the main reason for their preferring salads, and ‘because of vegetables in salad’ and ‘not knowing the necessity of eating salad’ as the main reasons. Compared to the HFG and MFG, the proportion of students responding ‘less than twice a week’ for vegetable and fruit consumption and ‘more than 2 hours/day on the internet/games’ was higher, while the preferences for namul, salads, saengchae, baechukimchi, chonggakkimchi, nabakkimchi, and fruits were lower in the LFG. The numbers of unfamiliar vegetables and dressings were lower in the HFG than in the other groups and were negatively correlated with the frequency of fruit and vegetable consumption and the preferences for aengchaes, bokkeum, salad, and namul. Also, this study compared the preferences for 14 vegetables and 9 dressings as ingredients of salads by gender, grade, and frequency of eating salads.

A total of 535 4th∼6th grade students in the Gyeonggi area were surveyed in an effort to increase vegetable preference and intake. They were divided into 3 groups according to the frequency of salad consumption (High-frequency group, HF, more than once a week G; Intermediate-frequency, IFG, 1∼3 times/month;Low-frequency group, LFG, less than once a month). The proportion of subjects who preferred salad over other vegetable dishes was much lower in the LFG than in the other groups. Compared to the HFG, more students in the LFG gave ‘dressing’ as the main reason for their preferring salads, and ‘because of vegetables in salad’ and ‘not knowing the necessity of eating salad’ as the main reasons. Compared to the HFG and MFG, the proportion of students responding ‘less than twice a week’ for vegetable and fruit consumption and ‘more than 2 hours/day on the internet/games’ was higher, while the preferences for namul, salads, saengchae, baechukimchi, chonggakkimchi, nabakkimchi, and fruits were lower in the LFG. The numbers of unfamiliar vegetables and dressings were lower in the HFG than in the other groups and were negatively correlated with the frequency of fruit and vegetable consumption and the preferences for aengchaes, bokkeum, salad, and namul. Also, this study compared the preferences for 14 vegetables and 9 dressings as ingredients of salads by gender, grade, and frequency of eating salads.

A total of 535 4th∼6th grade students in the Gyeonggi area were surveyed in an effort to increase vegetable preference and intake. They were divided into 3 groups according to the frequency of salad consumption (High-frequency group, HF, more than once a week G; Intermediate-frequency, IFG, 1∼3 times/month;Low-frequency group, LFG, less than once a month). The proportion of subjects who preferred salad over other vegetable dishes was much lower in the LFG than in the other groups. Compared to the HFG, more students in the LFG gave ‘dressing’ as the main reason for their preferring salads, and ‘because of vegetables in salad’ and ‘not knowing the necessity of eating salad’ as the main reasons. Compared to the HFG and MFG, the proportion of students responding ‘less than twice a week’ for vegetable and fruit consumption and ‘more than 2 hours/day on the internet/games’ was higher, while the preferences for namul, salads, saengchae, baechukimchi, chonggakkimchi, nabakkimchi, and fruits were lower in the LFG. The numbers of unfamiliar vegetables and dressings were lower in the HFG than in the other groups and were negatively correlated with the frequency of fruit and vegetable consumption and the preferences for aengchaes, bokkeum, salad, and namul. Also, this study compared the preferences for 14 vegetables and 9 dressings as ingredients of salads by gender, grade, and frequency of eating salads.

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer's disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Abeta) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Abeta-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Abeta-induced neurotoxicity. In mice with Abeta-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Abeta-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 microg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.
Acetylcholinesterase ; Alzheimer Disease ; Amyloid ; Animals ; Calcium ; Cholinergic Antagonists ; Dementia ; Herbal Medicine ; Hippocampus ; Homeostasis ; Houttuynia* ; Inhibitory Concentration 50 ; Memory ; Mice ; Neurons ; Phosphorylation ; Rats ; Tauopathies ; Water

BACKGROUND AND OBJECTIVES: Treatment with mesenchymal stem cells (MSC) in spinal cord injury (SCI) has been highlighted as therapeutic candidate for SCI. Although astrogliosis is a major phenomenon after SCI, the role of astrogliosis is still controversial. In this study, we determined whether acute transplantation of MSC improves the outcome of SCI through modulating astrogliosis. METHODS: Bone marrow derived rat MSCs were induced neural differentiation and transplanted after acute SCI rats. Matrix metalloproteinase (MMP) and neuro-inflammatory pathway were analyzed for acute astrogliosis at 1, 3 and 7 d after SCI in RT-PCR- and western blot analysis. Functional outcome was assessed serially at postoperative 1 d and weekly for 4 weeks. Histopathologic analysis was undertaken at 7 and 28 d following injury in immunohistochemistry. RESULTS: Transplantation of MSCs decreased IL-1α, CXCL-2, CXCL-10, TNF-α and TGF-β in a rat model of contusive SCI. Protein level of NF-κB p65 was slightly decreased while level of STAT-3 was increased. In immunohistochemistry, MSC transplantation increased acute astrogliosis whereas attenuated scar formation with increased sparing white matter of spinal cord lesions. In RT-PCR analysis, mRNA levels of MMP2 was significantly increased in MSC transplanted rats. In BBB locomotor scale, the rats of MSC treated group exhibited improvement of functional recovery. CONCLUSIONS: Transplantation of MSC reduces the inflammatory reaction and modulates astrogliosis via MMP2/STAT3 pathway leading to improve functional recovery after SCI in rats.
Animals ; Blotting, Western ; Bone Marrow ; Cicatrix ; Immunohistochemistry ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; Models, Animal ; Rats ; RNA, Messenger ; Spinal Cord Injuries ; Spinal Cord ; White Matter

BACKGROUND: Idiopathic pulmonary fibrosis involves irreversible alveolar destruction. Although alveolar epithelial type II cells are key functional participants within the lung parenchyma, how epithelial cells are affected upon bleomycin (BLM) exposure remains unknown. In this study, we determined whether BLM could induce cell cycle arrest via regulation of Schlafen (SLFN) family genes, a group of cell cycle regulators known to mediate growth-inhibitory responses and apoptosis in alveolar epithelial type II cells. METHODS: Mouse AE II cell line MLE-12 were exposed to 1–10 µg/mL BLM and 0.01–100 µM baicalein (Bai), a G1/G2 cell cycle inhibitor, for 24 hours. Cell viability and levels of pro-inflammatory cytokines were analyzed by MTT and enzyme-linked immunosorbent assay, respectively. Apoptosis-related gene expression was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Cellular morphology was determined after DAPI and Hoechst 33258 staining. To verify cell cycle arrest, propidium iodide (PI) staining was performed for MLE-12 after exposure to BLM. RESULTS: BLM decreased the proliferation of MLE-12 cells. However, it significantly increased expression levels of interleukin 6, tumor necrosis factor α, and transforming growth factor β1. Based on Hoechst 33258 staining, BLM induced condensation of nuclear and fragmentation. Based on DAPI and PI staining, BLM significantly increased the size of nuclei and induced G2/M phase cell cycle arrest. Results of qRT-PCR analysis revealed that BLM increased mRNA levels of BAX but decreased those of Bcl2. In addition, BLM/Bai increased mRNA levels of p53, p21, SLFN1, 2, 4 of Schlafen family. CONCLUSION: BLM exposure affects pulmonary epithelial type II cells, resulting in decreased proliferation possibly through apoptotic and cell cycle arrest associated signaling.
Animals ; Apoptosis ; Bisbenzimidazole ; Bleomycin ; Cell Cycle Checkpoints ; Cell Cycle ; Cell Line ; Cell Survival ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells ; Gene Expression ; Genes, vif ; Humans ; Idiopathic Pulmonary Fibrosis ; Interleukin-6 ; Lung ; Mice ; Propidium ; RNA, Messenger ; Transforming Growth Factors ; Tumor Necrosis Factor-alpha

BACKGROUND: Idiopathic pulmonary fibrosis involves irreversible alveolar destruction. Although alveolar epithelial type II cells are key functional participants within the lung parenchyma, how epithelial cells are affected upon bleomycin (BLM) exposure remains unknown. In this study, we determined whether BLM could induce cell cycle arrest via regulation of Schlafen (SLFN) family genes, a group of cell cycle regulators known to mediate growth-inhibitory responses and apoptosis in alveolar epithelial type II cells. METHODS: Mouse AE II cell line MLE-12 were exposed to 1–10 µg/mL BLM and 0.01–100 µM baicalein (Bai), a G1/G2 cell cycle inhibitor, for 24 hours. Cell viability and levels of pro-inflammatory cytokines were analyzed by MTT and enzyme-linked immunosorbent assay, respectively. Apoptosis-related gene expression was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Cellular morphology was determined after DAPI and Hoechst 33258 staining. To verify cell cycle arrest, propidium iodide (PI) staining was performed for MLE-12 after exposure to BLM. RESULTS: BLM decreased the proliferation of MLE-12 cells. However, it significantly increased expression levels of interleukin 6, tumor necrosis factor α, and transforming growth factor β1. Based on Hoechst 33258 staining, BLM induced condensation of nuclear and fragmentation. Based on DAPI and PI staining, BLM significantly increased the size of nuclei and induced G2/M phase cell cycle arrest. Results of qRT-PCR analysis revealed that BLM increased mRNA levels of BAX but decreased those of Bcl2. In addition, BLM/Bai increased mRNA levels of p53, p21, SLFN1, 2, 4 of Schlafen family. CONCLUSION BLM exposure affects pulmonary epithelial type II cells, resulting in decreased proliferation possibly through apoptotic and cell cycle arrest associated signaling.