Vasoactive Intestinal Peptide Receptor, CRTH2, Antagonist Treatment Improves Eosinophil and Mast Cell-Mediated Esophageal Remodeling and Motility Dysfunction in Eosinophilic Esophagitis.

BACKGROUND AND AIMS: Ultrasonography has shown that eosinophils accumulate in each segment of the esophageal mucosa in human EoE, ultimately promoting esophageal motility dysfunction; however, no mechanistic evidence explains how or why this accumulation occurs. METHODS: Quantitative PCR, ELISA, flow cytometry, immunostaining, and immunofluorescence analyses were performed using antibodies specific to the related antigens and receptors. RESULTS: In deep esophageal biopsies of EoE patients, eosinophils and mast cells accumulate adjacent to nerve cell-derived VIP in each esophageal segment. qRT-PCR analysis revealed five- to sixfold increases in expression levels of VIP, CRTH2, and VAPC2 receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA CRTH2 levels and eosinophil- and nerve cell-derived VIPs in human EoE (p < 0.05). We provide evidence that eosinophil and mast cell deficiency following CRTH2 antagonist treatment improves motility dysfunction in a chronic DOX-inducible CC10-IL-13 murine model of experimental EoE. CONCLUSIONS: CRTH2 antagonist treatment is a novel therapeutic strategy for inflammatory cell-induced esophageal motility dysfunction in IL-13-induced chronic experimental EoE.

Prominent role of histone lysine demethylases in cancer epigenetics and therapy.

Protein methylation has an important role in the regulation of chromatin, gene expression and regulation. The protein methyl transferases are genetically altered in various human cancers. The enzymes that remove histone methylation have led to increased awareness of protein interactions as potential drug targets. Specifically, Lysine Specific Demethylases (LSD) removes methylated histone H3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) through formaldehyde-generating oxidation. It has been reported that LSD1 and its downstream targets are involved in tumor-cell growth and metastasis. Functional studies of LSD1 indicate that it regulates activation and inhibition of gene transcription in the nucleus. Here we made a discussion about the summary of histone lysine demethylase and their functions in various human cancers.

Synergistic antitumor effect of combined paclitaxel with FEN1 inhibitor in cervical cancer cells.

Studies on cervical cancer are urgently required to improve clinical outcomes. As a major anticancer drug for cervical cancer, paclitaxel has been used for many years in clinical therapy but its therapeutic efficacy is limited by common obstacle from cancer cells. The enhanced DNA repair pathways of cancer cells have been proved to survive DNA damage induced by chemotherapeutic drug. Inhibitors of specific DNA repair pathway can sensitize cancer cells to the treatment of chemotherapeutic drugs. In this paper we found that the effect of paclitaxel can be significantly improved when used in combination with FEN1 inhibitor SC13, suggesting a synergistic mechanism between the two compounds. Our studies suggest that FEN1 inhibition could be a novel strategy of tumor-targeting therapy for cervical cancer. Our work also revealed that paclitaxel demonstrates stronger synergistic effect with SC13 than other common used chemical drugs such as doxorubicin, carboplatin or camptothecin on cervical cancer cells.

Proteomic characterization and bio-informatic analysis of differentially expressed E. coli Nissle 1917 proteins with response to cocoti wine stress.

The present study emphases the comparative proteomic analysis of Escherichia coli Nissle 1917 under cocoti palm wine stress and identified differentially expressed proteins. Protein samples were analyzed by 2-D, MALDI-TOF combined with MS access. In 2-D electrophoresis, eight differentially expressed proteins were identified: five up-regulated, two down-regulated and one newly expressed protein. Protein spots were digested with trypsin for MALDI-TOF-MS analysis; protein sequences were obtained from MASCOT search. Sequences were aligned with template using Swiss Model server. Phyre-2 was used to predict homology modeling, RasMol was used to analyze the modeling structures, PSVS server was utilized to validate the protein structure by Ramachandran's plot analysis, physical and chemical properties were analyzed using ProtParam server, Phylogenetic tree was constructed by Mega4. UniProt search helps to find protein functional information of differentially expressed proteins, involved in catalytic activities, regulation mechanisms, DNA damage stimulus, anti-termination and termination process, protein binding, electron transport mechanism, and cell signaling process functions. A detailed exploration of the proteins under cocoti palm wine stress have provided the composition, structure and functions of the expressed proteins for further investigation.

Interacting partners of FEN1 and its role in the development of anticancer therapeutics.

Protein-protein interaction (PPI) plays a key role in cellular communication, Protein-protein interaction connected with each other with hubs and nods involved in signaling pathways. These interactions used to develop network based biomarkers for early diagnosis of cancer. FEN1(Flap endonuclease 1) is a central component in cellular metabolism, over expression and decrease of FEN1 levels may cause cancer, these regulation changes of Flap endonuclease 1reported in many cancer cells, to consider this data may needs to develop a network based biomarker. The current review focused on types of PPI, based on nature, detection methods and its role in cancer. Interacting partners of Flap endonuclease 1 role in DNA replication repair and development of anticancer therapeutics based on Protein-protein interaction data.

Surfacing role of probiotics in cancer prophylaxis and therapy: A systematic review.

Cancers figure among the most important causes of morbidity and mortality worldwide. Cancer and its associated infections are always complicated even when specific cancer regimens are available. It is well proved that Lactobacillus and other probiotic bacteria can modulate-ameliorate specific mechanisms against various infections including cancers. The present systematic review is intended to focus on the 'cellular and molecular mechanisms' of probiotic bacteria in the prevention and treatment of various cancers. The clinical and experimental findings of various studies explain the mechanisms such as apoptosis, antioxidant activity, immune response and epigenetics and illustrate the role of probiotics in cancer management and prophylaxis. In addition, the present review also discusses the safety aspects of probiotics when they are used in therapeutic and nutritional diet management. However, further investigations are required to reveal the effectiveness of probiotics in cancer treatment in clinical settings.