Implantation of the blastocyst stage embryo into the maternal endometrium is a critical determinant and a rate-limiting process for successful pregnancy. Embryo implantation requires synchronized changes in the endometrium before and after arrival of blastocyst into the uterine cavity. Extensive cross talks occur between the fetal and maternal compartments around the time of implantation which are reflected by morphologic, biochemical and molecular changes in the endometrial cells and the differentiating trophoblast cells. The embryo induced morphologic changes include occurrence of epithelial plaque reaction, stromal compaction and decidualization. Embryonic signals also alter the expression of a large number of transcription factors, growth factors and their receptors and integrins. Thus the embryo superimposes a unique signature on the receptive endometrium for successful implantation. Functionally, the embryo-endometrial cross talk is essential for endowing a “selector activity” to the receptive endometrium to ensure implantation of only a developmentally competent embryo. On selection, the decidua creates a conducive microenvironment for trophoblast invasion leading to placentation. Clinical evidences suggest that along with receptivity, a defective “selector” activity of the receptive uterus may be a cause of infertility and recurrent miscarriages. Defects in trophoblast invasion are associated with pregnancy complications like preeclampsia and intra-uterine growth retardation. It is envisaged that understanding of the embryo-endometrial dialogue leading to the “selector” activity, aids in development of appropriate therapeutic modalities for infertility related disorders and miscarriages. Conversely, it might also benefit the development of anti-implantation drugs for contraception.

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In vitro co-culture system consisting of bone marrow stromal cells (BMSCs) or mesenchymal stromal cell lines of marrow origin has provided important clues about the regulation of hematopoietic stem cells (HSCs) by their microenvironment or niche. In the current studies, we have compared phenotypic and functional characters of a marrow-derived mesenchymal stem cell line, M210B4, with BMSCs. We demonstrate that M210B4 resembles BMSCs in terms of phenotypic characters. Unlike the BMSCs, M210B4 differentiated only towards adipogenic lineage, and was refractory towards osteogenic differentiation. However, M210B4 cells exhibited a higher HSC-supportive ability as assessed by flow cytometry analyses of the output cells from co-cultures. We observed that M210B4 cells show a constitutively higher activation of p44/42 and p38 MAPK pathways compared to BMSCs, contributing to their higher HSC-support in vitro. Overall, the results show that M210B4 forms a suitable in vitro system to study HSC regulation in vitro.

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Radiotherapy remains the standard treatment for glioblastoma multiforme (GBM) following surgical resection. Given the aberrant expression of human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) which may play a role in therapeutic resistance to receptor tyrosine kinase inhibitors, and the emerging use of histone deacetylase (HDAC) inhibitors as radiosensitizers, we defined the effects of CUDC-101, a triple inhibitor of HER2, EGFR and HDAC on the radiosensitivity of GBM cells. Clonogenic survival was used to determine the in vitro radiosensitizing potential of CUDC-101 on GBM, breast cancer, and normal fibroblast cell lines. Inhibitory activity was defined using immunoblots and DNA double strand breaks were evaluated using yH2AX foci. Effects of CUDC-101 on cell cycle and radiation-induced cell kill were determined using flow cytometry and fluorescent microscopy. CUDC-101 inhibited HER2, EGFR and HDAC and enhanced in vitro radiosensitivity of both GBM and breast cancer cell lines, with no effect on normal fibroblasts. Retention of yH2AX foci was increased by CUDC-101 alone and in combination with irradiation for 24 h. Treatment with CUDC-101 increased the number of cells in G2 and M phase, with only increase in M phase statistically significant. An increase in mitotic catastrophe was seen in a time-dependent fashion with combination treatment. The results indicate the tumor specific CUDC-101 enhanced radiosensitization in GBM, and suggest that the effect involves inhibition of DNA repair.

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Tissue stem cells self-renew throughout the life of an organism thereby maintaining tissue homeostasis and prevent cancer. The major signalling pathways such as Wnt, Notch and Sonic hedgehog control the stem cell regulation and their deregulation leads to cancer. Recent evidences showed that there exists a subset of cells within tumour termed as cancer stem cells (CSCs). These CSCs escape the conventional chemo-radiotherapy and further lead to tumour relapse followed by metastasis. This review focuses on the developmental signalling pathways that are involved in the regulation and maintenance of normal stem cells and CSCs. Understanding the molecular mechanism may be useful to specifically target the CSCs while sparing the normal stem cells to reduce tumorigenecity.

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The role of transcription factor, nuclear factor [erythroid-derived 2]-like 2 (Nrf2), is detoxification of xenobiotics, overcoming oxidative stress and offering resistance to ionizing radiation induced cell death. However, the role of Nrf2 in cancer progression remains debatable. Activation of Nrf2 dependent proteins is crucial in maintaining cellular redox homeostasis and combating toxicity of carcinogens. Thus, employing natural or synthetic activators of Nrf2 pathway is a promising approach for development of chemopreventive modalities. Intriguingly, recent reports have highlighted the dark side of Nrf2 suggesting that multiple cancer cells demonstrate constitutive activation of Nrf2 caused by mutations in Nrf2 or Keap-1 proteins, offering survival advantage. Additionally, Nrf2 pathway is also up-regulated in chemoresistant cells and may be a major contributor in acquired chemoresistance. Thus, targeting Nrf2 pathway has emerged as a novel strategy to improve efficacy of chemotherapeutic drugs. This review discusses the dark and bright sides of this transcription factor in line with the recent literature.

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Electrochemical biosensors are portable devices that permit rapid detection and monitoring of biological, chemical and toxic substances. In the electrochemical biosensors, the bioreceptor is incorporated into the transducer surface; and when in contact with the analyte, generates measurable signals proportional to the analyte concentration. Materials with high surface area, high reactivity, and easy dispersability, are most suited for use in biosensors. Dendrimers are nanomaterial gaining importance for fabrication of electrochemical biosensors. These are synthetic macromolecules with regularly branched tree-like and globular structure. The potential applications of dendrimers as biosensors are explored due to their geometric symmetrical structure, chemical stability, controlled shape and size, and varied surface functionalities, with adequate functional groups for chemical fixation. The current review provides multi-faceted use of dendrimers for developing effective, rapid, and versatile electrochemical sensors for biomolecules. The redox centers in the dendrimers play an important role in the electron transfer process during immobilization of biomolecules on the electrodes. This has led to an intensive use of dendrimer based materials for fabrication of electrochemical sensors with improved analytical parameters. The review emphasizes development of new methods and applications of electrochemical biosensors based on novel nanomaterials.

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Glioblastoma multiforme (GBM) is one of the most lethal human cancers and poses a great challenge in the therapeutic interventions of GBM patients worldwide. Despite prominent recent advances in oncology, on an average GBM patients survive 12–15 months with conventional standard of care treatment. To understand the pathophysiology of this disease, recently the research focus has been on omics-based approaches. Advances in high-throughput assay development and bioinformatic techniques have provided new opportunities in the molecular analysis of cancer omics technologies including genomics, transcriptomics, epigenomics, proteomics, and metabolomics. Further, the enormous addition and accessibility of public databases with associated clinical demographic information including tumor histology, patient response and outcome, have profoundly improved our knowledge of the molecular mechanisms driving cancer. In GBM, omics have significantly aided in defining the molecular architecture of tumorigenesis, uncovering relevant subsets of patients whose disease may require different treatments. In this review, we focus on the unique advantages of multifaceted omics technologies and discuss the implications on translational GBM research.

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