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The aim of this study was to investigate the cellular changes induced by spontaneous/replicative senescence and radiation in human osteoblasts (OBs), and the impact of cultivation with nicotinamide mononucleotide (NMN) and platelet-rich fibrin (PRF) on apoptosis, senescence-associated ß-galactosidase staining (SA ß-gal), and senescence-related gene expression using RT2 Profiler PCR array. The results showed that replicative OB aging follows a different pattern from that of radiation-induced cellular senescence. SA ß-gal intensity score showed a significant elevation after spontaneous replicative aging of OB (agiT1) 7 days following the start of the experiment, compared with their initial control condition (T0) (T0 = 2.1 ± 0.47; agiT1 = 9.60 ± 1.56; p = 0.001). Concurrent treatment by NMN and PRF showed a protective effect on OBs undergoing replicative senescence, and reduced SA ß-gal staining significantly (agiT1 = 9.60 ± 1.56; agiT1+PRF = 3.19 ± 0.52; agiT1+NMN = 3.38 ± 0.36; p < 0.001). These results provide evidence for the potential clinical implications of systematic NMN administration and local PRF application to prevent age-related bone disturbances in elderly patients.

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BACKGROUND: Oil tea is a type of traditional tea beverage used for treating various ailments in minority population in Guangxi, China. Our previous study showed oil tea improved glucose and lipid levels in type 2 diabetic mice. Yet, the underling molecular mechanisms are still not understood. This study aimed at assessing the effect of oil tea on glucose homeostasis and elucidating the molecular mechanisms underlying the oil tea-induced antidiabetic effects. METHODS: Twenty seven db/db mice were gavaged with saline, metformin and oil tea for 8 weeks with measurement of biochemical profiles. A real-time2 (RT2) profiler polymerase chain reaction (PCR) array comprising 84 genes involved in glucose metabolism was measured and validated by quantitative PCR (qPCR). The association between the candidate genes and type 2 diabetes were further analyzed in a case-control study in the Chinese minority population. RESULTS: Oil tea treatment facilitated glucose homeostasis by decreasing fasting blood glucose and total cholesterol, and improving glucose tolerance. Suppressing phosphoenolpyruvate carboxykinase 1 (PCK1) expression was observed in the oil tea treatment group and the expression was significantly correlated with fasting blood glucose levels. Target prediction and functional annotation by WEB-based GEne SeT AnaLysis Toolkit (WebGestalt) revealed that PCK1 mainly involved in the glycolysis/gluconeogenesis pathway among the top Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathways. Both rs707555 and rs2071023 in PCK1 were significantly associated with type 2 diabetes in the minority population of Guangxi. CONCLUSION: Our findings indicated oil tea improved glucose homeostasis via down-regulation of PCK1 and PCK1 may be a genetic marker for the treatment of type 2 diabetes.

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BACKGROUND: Toll-like receptors (TLRs) play a significant role based on innate immune mechanism during viral infection. TLR signaling mechanism designates to protect the cells from invading viruses. The expression of TLRs during dengue virus (DENV) infection not yet well explained. This study evaluates the TLR gene expression from DENV-infected patient's cornea. METHODS: Reverse transcriptase PCR was performed for the detection and genotyping of viral nucleic acid from corneal grafts and DENV-infected cell suspension. TLR expression studies were done on DENV-infected cornea by real-time RT2 Profiler PCR Array. RESULTS: The reverse transcriptase PCR and genotyping confirmed the presence of DENV-3. TLR expression studies revealed the upregulated expression of TLR4, TLR7, TLR9 and TLR10. CONCLUSION: Molecular testing of DENV reveals that serological positivity induces transmission of the virus through cornea and stimulates the expression of TLR4, TLR7, TLR9 and TLR10, which may lead to up-regulation of innate pro-inflammatory response in the cornea.

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The Wnt signaling pathway and its key component ß-catenin have critical roles in the development of diseases such as tumors in mammals. However, little has been reported about involvement of the Wnt/ß-catenin signaling pathway in canine mammary tumors (CMTs). The present study detected expression of 30 Wnt signaling pathway-related genes in CMTs; the results are potentially useful for molecular-based diagnosis of CMTs and the development of new targeted therapies. Significant upregulations of dickkopf-1 protein, secreted frizzled-related sequence protein 1 (SFRP1), frizzled 3, ß-catenin, and lymphoid enhancer-binding factor 1 (LEF1) were detected in highly malignant CMTs compared to levels in normal mammary gland tissues; moreover, highly significant upregulation of WNT5A was observed in low malignancy CMTs. Downregulation was only detected for SFRP4 in malignant CMT samples. The subcellular location of ß-catenin and cyclin D1 in 100 CMT samples was investigated via immunohistochemical analysis, and significantly increased expressions of ß-catenin in cytoplasm and cyclin D1 in nuclei were revealed. Western blotting analysis revealed that the expression of ß-catenin and LEF1 increased in in the majority of CMT samples. Taken together, the results provide important evidence of the activation status of the Wnt pathway in CMTs and valuable clues to identifying biomarkers for molecular-based diagnosis of CMT.

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The Wnt signaling pathway and its key component β-catenin have critical roles in the development of diseases such as tumors in mammals. However, little has been reported about involvement of the Wnt/β-catenin signaling pathway in canine mammary tumors (CMTs). The present study detected expression of 30 Wnt signaling pathway-related genes in CMTs; the results are potentially useful for molecular-based diagnosis of CMTs and the development of new targeted therapies. Significant upregulations of dickkopf-1 protein, secreted frizzled-related sequence protein 1 (SFRP1), frizzled 3, β-catenin, and lymphoid enhancer-binding factor 1 (LEF1) were detected in highly malignant CMTs compared to levels in normal mammary gland tissues; moreover, highly significant upregulation of WNT5A was observed in low malignancy CMTs. Downregulation was only detected for SFRP4 in malignant CMT samples. The subcellular location of β-catenin and cyclin D1 in 100 CMT samples was investigated via immunohistochemical analysis, and significantly increased expressions of β-catenin in cytoplasm and cyclin D1 in nuclei were revealed. Western blotting analysis revealed that the expression of β-catenin and LEF1 increased in in the majority of CMT samples. Taken together, the results provide important evidence of the activation status of the Wnt pathway in CMTs and valuable clues to identifying biomarkers for molecular-based diagnosis of CMT.

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Icariin, an ingredient in the medicinal herb Epimedium brevicornum Maxim (EbM), has been considered as a potential therapeutic agent for neurodegenerative diseases such as Alzheimer's disease (AD). Hyperhomocysteinaemia is a risk factor for AD and other associated neurological diseases. In this study we aim to investigate whether icariin can reverse homocysteine (Hcy)-induced neurotoxicity in primary embryonic cultures of rat cortical neurons. Our findings demonstrated that icariin might be able restore the cytoskeleton network damaged by Hcy through the modulation of acetyl-α-tubulin, tyrosinated-α-tubulin, and phosphorylation of the tubulin-binding protein Tau. In addition, icariin downregulated p-extracellular signal-regulated kinase (ERK) which is a kinase targeting tau protein. Furthermore, icariin effectively restored the neuroprotective protein p-Akt that was downregulated by Hcy. We also applied RT² Profiler PCR Arrays focused on genes related to AD and neurotoxicity to examine genes differentially altered by Hcy or icariin. Among the altered genes from the arrays, ADAM9 was downregulated 15 folds in cells treated with Hcy, but markedly restored by icariin. ADAM family, encoded α-secreatase, plays a protective role in AD. Overall, our findings demonstrated that icariin exhibits a strong neuroprotective function and have potential for future development for drug treating neurological disorders, such as AD.

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PURPOSE: To investigate effect of embelin on proliferation, apoptosis and gene expression profile changes in breast cancer cells. METHODS: Cell viability was determined by MTT assay and apoptosis assayed using flow cytometry. Differential expression of 84 genes commonly involved in breast cancer carcinogenesis was assessed by real-time PCR using the Human Breast Cancer RT(2) Profiler PCR Array. RESULTS: MCF-7 and MDA-MB-231 cells were treated with embelin (0-25µM) for 24 and 96h. Embelin exhibited time and dose dependence in both cell lines and was more potent in inhibiting MDA-MB-231 cell proliferation compared to MCF-7 cells. IC50 for embelin in MDA-MB-231 cells was ∼4.45µM and 3.28µM at 24h and 96h, respectively. In contrast, IC50 for embelin in MCF-7 cells was ∼6.04µM and 4.51µM at 24h and 96h, respectively. Embelin (50µM) induced apoptosis and activated caspase 3 activity in both cell lines when exposed for 72h. Treatment of MDA-MB-231 cells with embelin (10µM) for 24h resulted in significant differential expression of 27 genes commonly involved in breast cancer carcinogenesis. CONCLUSIONS: Our findings show that embelin inhibits cell proliferation, induces apoptosis and alters expression of breast cancer focused genes in MCF-7 and MDA-MB-231 cells. Based on RT(2)-PCR array analysis, embelin down-regulated expression of pivotal oncogenes. This knowledge could be beneficial in the development of effective embelin-based therapies for treating breast cancer.

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Metabolic reprogramming plays a crucial role in the development of cancer. The aim of this study was to explore the effect of fenofibrate, an agonist of peroxisome proliferator-activated receptor alpha (PPARα), on gene expression profiles of mitochondrial energy metabolism. Our results showed that PPARα expression was negatively correlated with tumor progression in an oral cancer mouse model. Activation of PPARα through fenofibrate suppressed migration of oral cancer cells. Differential protein profiling demonstrated that expressions of genes related to mitochondrial energy metabolism were either up-regulated (Atp5g3, Cyc1, Ndufa5, Ndufa10, and Sdhd) or down-regulated (Cox5b, Ndufa1, Ndufb7, and Uqcrh) through PPARα activation and response. Our results indicate that PPARα exhibits a great potential for anti-oral cancer therapies by modulating cancer cell mitochondrial energy metabolism.