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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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Neonatal tissues, cord and placenta, are explored as alternate sources of mesenchymal stem cells (MSCs) for their therapeutic applications. Conventionally, MSCs isolated from cord tissues are maintained and propagated in FBS containing medium for promotion of growth and survival of cells. However, for therapeutic use, FBS use is not encouraged as it is of animal origin. Thus, there is a need for replacement of FBS by equally potent and clinically acceptable cost effective sources. The current study is designed to compare the effect of cord blood plasma (CBP) with MSC qualified FBS (M FBS) during culture and cryopreservation of MSCs. MSCs were isolated from cord and placenta and propagated in either M FBS or CBP. The efficiency of the cultures was analyzed by growth curve, morphology, phenotype and functionality. The cryo-protective role of the CBP was evaluated by using it in freezing medium of MSCs. Our data showed that CBP is equivalent to M FBS for culturing placental MSCs with respect to the phenotype, proliferation rate and differentiation to various lineages. However, cord MSCs displayed slow growth rate and reduction in surface expression of CD105 marker in CBP, whereas, the other parameters were comparable. Freezing of MSCs with CBP resulted in reduction of the late apoptotic and necrotic population. Thus, CBP imparts superior protection against cryogenic insults, and appears to be a valuable substitute to M FBS for cultivation and freezing of MSCs.

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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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Certain excitable cells, such as those in cardiac and smooth muscle, are known to form electrical syncytia. Cells within a syncytium are coupled to adjacent cells by means of structures known as gap junctions, which provide electrical continuity between cells. This results in the spread and propagation of electrical activity, such as action potentials (APs), from the originating cell to other cells in its syncytium. We propose that this ability of APs to propagate through an electrical syncytium depends on various syncytial features, and also the AP profile. The current study attempts to investigate these various factors using a computational approach. Simulations were conducted on a model of a three-dimensional syncytium using the NEURON simulation platform. The results confirm that the capacity of action potentials to propagate in a syncytium is influenced by the features of the action potential, and also the arrangement of cells within the syncytium. The excitability of biophysically identical cells was found to differ based on the size of the syncytium, their location within it, and the extent of gap junctional coupling between neighboring cells. Only a window of gap junctional coupling levels allowed both the initiation and propagation of action potentials. The results clearly exhibit the role of AP diversity and syncytial features in determining the spread of action potentials. This has significant implications for understanding the functioning of syncytial tissues, such as the detrusor smooth muscle, both in physiology and in disease.

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Although human and murine Endothelial Progenitor Cells (EPCs) are routinely used for research, the results can only be imperfectly analyzed due to our limited understanding of source-specific differential responses to stress. Although the routinely used cellular and functional assays are effective for detection of EPC dysfunction (EPD) in single source test systems, there is lack of a universal detection system capable of detecting high glucose (HG) and/or Diabetes mellitus (DM)-induced EPD irrespective of source or site. To remedy this lacuna we compared the test systems from both cell sources. Comparison of sensitivity of various cellular assays revealed that of all the assays performed, only colony formation assays (CFU) showed comparable responses to diabetes/high glucose in both test systems, while cell adhesion assay (CAA), proliferation potential and viability differed in their responses to HG. On the other hand, the functional assays i.e. tubule formation, chemotactic migration assay and CXCR4 and VEGFR2 mRNA expression were uniformly affected by HG in vitro and DM in vivo. Interestingly, other parameters studied i.e. nitric oxide, reactive oxygen species (ROS) and manganese superoxide dismutase (MnSOD) showed dissimilar responses to HG and DM exposure. On this basis, we propose a panel of assays comprising CFU, tubule formation, chemotactic-migration and CXCR4 and VEGFR2 mRNA expression that can accurately detect HG-/DM-induced EPD irrespective of various systemic factors. These assays will also enhance uniformity across data sets and increase accuracy of EPD detection in human and murine systems.

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Ovarian cancer is the fifth leading cause of cancer related deaths in women with a five year survival rate of only 30–40%. Amongst the three broad subgroups of ovarian cancer, epithelial ovarian cancer is the most common and is divided in mainly five subtypes based histology and clinical behaviour. In patients when the disease is still confined to ovaries, surgery alone is curative for more than 90% patients. Unfortunately, most women are diagnosed with advanced stage disease and recurs in majority despite of debulking surgery and initial response to chemotherapy. Thus ovarian cancer is still a challenge to clinicians which gets more complicated due to asymptomatic nature of the early stage disease and frequent development of resistance to standard therapies. Therefore, researchers worldwide are engaged in identifying markers for early detection of ovarian cancer, investigating molecular mechanisms of chemoresistance, improving detection methods and developing novel therapeutic measures. In this review, we attempt to discuss the contemporary research and challenges associated with epithelial ovarian cancer along with the future improvements in various areas such as early detection of ovarian cancer through Multiplex-Methylation specific PCR (MSP) assay and Serial Analysis of Gene expression (SAGE) assay and identifying new biomarkers, facilitating personalised chemotherapy regime by various chemo-response assays, novel drugs and targeted therapies which will aid in enhancing the overall survival rate in future and overcome this deadly gynaecologic disease.

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Areca nut is widely used in India and the consumption has increased over the past two decades, with availability in new dry packaged forms (pan masala, gutka, mawa). Recent reports of increasing mouth cancer incidence have suggested an association with areca nut consumption. Here we have reviewed the evidence for carcinogenicity of areca nut, including epidemiological studies, several animal studies and mechanistic evidence. Studies primarily from India, providing odds ratios (ORs) or relative risks for precancers or cancer with use of areca nut without inclusion of tobacco is the focus of the review. Six case-control studies on oral submucous fibrosis (OSF) had significantly elevated ORs for use of areca nut in various forms. Six case-control studies on head and neck cancers, primarily oral cancer reported elevated ORs for chewing of betel quid without tobacco. Eight case control studies on oral cancer have reported elevated and significant ORs for betel quid with tobacco. A significant risk in oral cancer was noted in gutka users. Animal studies confirmed correlation between development of precancers or cancers and exposure to areca nut or pan masala without tobacco. Mechanistic evidence shows a role for areca nut alkaloids, polyphenols and copper in promoting carcinogenesis. Our review emphasizes control policies on areca nut products and appropriate mass communication programs for awareness of hazards of areca nut with emphasis on areca nut per se.

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Haematopoiesis is severely hampered after exposure to ionizing radiations. Role of polyunsaturated fatty acids (PUFAs) during embryonic development as well as during various physiological processes is well established. However, few studies on their effect on haematopoiesis are reported. Hence, we studied the effect of oral administration of PUFAs-AA/DHA on haematopoiesis of sub-lethally irradiated mice. To determine the optimal dose for haematopoiesis, non-irradiated healthy mice were orally fed with different doses of AA/DHA daily for ten days. Additionally, mice were sub lethally irradiated and kept for ten days on normal diet. Further, sub-lethally irradiated mice were orally fed with optimal dose of AA/DHA for ten days. Mice from the experiments were sacrificed after ten days and their bone marrow cells were harvested and analyzed for their total nucleated cell (TNC) count, side population (SP) and lin-Sca-1⁺c-kit⁺(LSK) phenotype. Peripheral blood collected from this set of mice was subjected to hemogram analysis. Daily dose of 8 mg AA/DHA for ten days was assessed as optimal for enhancing BM-MNCs and primitive HSCs in non-irradiated mice. Significant depletion in BM-MNCs, SP and LSK cells was observed in sub lethally irradiated mice compared to un-irradiated control mice. Feeding with DHA or AA in sub lethally irradiated mice showed significantly higher number of BM-MNCs and increased percentage of SP and LSK cells, suggesting that DHA and AA resulted in better recovery of hematopoietically compromised mice. The data indicated that DHA or AA may serve as useful dietary supplements in patients exposed to irradiation.

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Objective: Oral cancer, in India, constitutes 26% of global oral cancer burden. The major risk factors include tobacco, areca nut, alcohol, and human papillomavirus 16/18; however, only 5%–10% of the high-risk individuals develop oral cancer, indicating the role of genomic variants in susceptibility to oral cancer. Conventional treatment options in oral cancer have resulted in relatively poor prognosis and an unmet need of treatment. In silico analysis, therefore, was performed to identify small drug-like molecules as potential inhibitors of transforming growth factor beta-2 receptor (TGFβRII). Materials and Methods: Seven single-nucleotide polymorphisms (SNPs) were analyzed in 500 histopathologically confirmed oral cancer samples and 500 long-term tobacco users (LTTUs) as controls using allelic discrimination real-time polymerase chain reaction or high-resolution melting analysis. The differential frequencies in oral cancer and LTTUs were calculated using SPSS software (version 19), and odds ratio (OR) to indicate risk to oral cancer using Hutchon.net. structure-based virtual screening of drug-like molecules was performed to identify lead inhibitor molecules to TGFβRII using Schrödinger Suite 2015-4. Results: Heterozygous GC genotype of TGFBR2 rs9843143 demonstrated increased risk ([P = 0.011; OR 1.61 [1.25–2.1]) while CC genotype showed decreased risk (P = 0.005; OR 0.61 [0.44–0.83]) to oral cancer. Increased/decreased risk to oral cancer was not observed for the other SNPs. In silico analysis identified six molecules as inhibitors of TGFβRII kinase domain from 17,723 conformers from Maybridge HitFinder library and 2685 conformers from MEGx AnalytiCon natural product library. Conclusion: SNP rs9843143 (TGFBR2) demonstrated a significant association (P < 0.05) with oral cancer and six potential inhibitors of TGFβRII kinase were identified using in silico analysis.

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Gonadotropin-releasing hormone (GnRH) is secreted from hypothalamic neurons and bind to receptors on gonadotrope cells of the pituitary gland, which then synthesize and release luteinizing hormone and follicle-stimulating hormone that regulate gonadal development. The presence of GnRH receptors and the effects of synthetic analogs of GnRH at extrapituitary sites is less clear. Several reports suggest that GnRH/analogues through cognate receptors may regulate mitogenic responses in cancer cells in an autocrine or paracrine manner. However, the inherent intracellular signaling pathways triggered are unknown. Using a highly specific antibody to human GnRH receptor we show that T47D breast cancer cells express GnRH receptors on their surface and that a GnRH analogue Cetrorelix inhibits proliferation of these cells, possibly via inhibition of processes that trigger cAMP formation.

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Majority of human cancers are caused, mediated and modified by environmental and lifestyle factors; and the multi-factorial, multi-step and multi-path process of carcinogenesis involves a series of genetic and epigenetic events. In spite of tremendous advancement in understanding of the molecular basis of cancer and identification of several environmental carcinogens, avoidance of exposure to carcinogens and early detection and/or successful treatment for most cancers have met with limited success. Based on the susceptibility to modulations of the multi-step process of carcinogenesis by a multitude of environmental compounds, lifestyle changes and host factors, and the demonstrated success of prevention of certain infectious diseases and cardiovascular events, cancer preventive interventions are receiving increasing attention. Several cancer preventive interventions such as vaccination, chemoprevention, weight control and lifestyle changes have been implemented. The current review focuses on several approaches and agents that have been scrutinized by way of randomized clinical trials in humans for their cancer prevention potential. Successful chemopreventive agents include selective oestrogen receptor modulators and aromatase inhibitors for breast cancer, the 5-α-reductase inhibitors for prostate cancer, non-steroidal antiinflammatory drugs (NSAIDs) for colorectal lesions and vaccines for viruses that are associated with cervical and liver cancers. Several experimentally proven chemopreventive agents have been observed to lack efficacy with and without toxicity. In spite of numerous chemoprevention trials, the number of successful agents is rather small. Identifying novel approaches and chemopreventives holds tremendous potential for reducing the burden of cancer.

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The ability to artificially simulate the ‘mechanical’ niche, broadly termed as Extracellular Matrix (ECM), of the bone marrow determines success for stem cell growth, architectural organization and differentiation viz. tissue engineering. The advent of various natural and synthetic polymers has greatly influenced tissue engineering. The focus of the review is on various artificial niche simulations, ECM, scaffolds such as hydrogels, electrospun nano and micro fibers, bone-strengthening scaffolds and tissue infills. The utility of the ECMs in the treatment of various medical conditions including bone and cartilage tissues, nervous tissues, spinal cord and tendon tissues as well as wound healing, along with the ability of some ECMs in entrapment of elusive cell secretomes will be discussed. The future of tissue engineering has indeed got a new lease of life with polymer scaffolds and it is feasible that certain goals, thought of impossible so far, may become possible.

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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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Gene therapy is one of the promising therapeutic strategies evolved rapidly in the frontier of translational biology in cancer. To overcome the off target effect of conventional cancer therapies it is the most flourishing approach in present epoch. Various researches in this context are ongoing to eradicate devastating cancer cells with minimal or no side effects. Of the various gene therapy protocols developed, a set of genes called suicide genes, are being actively pursued as potential strategy. Briefly, this strategy involves tumor targeted delivery of a therapy/reporter gene to convert a systematically administered pro-drug into a cytotoxic drug which in turn induces tumor cell death. Additionally, advancement in small animal imaging modalities facilitates real-time monitoring of the delivered transgene by using appropriate imaging probe developed against the transgene. Non-invasive monitoring helps to realize precise transgene delivery and also aid to understand therapy response. In this background, we have reviewed potential suicide genes frequently explored for cancer treatment, which supports both diagnostic and therapeutic applications with special emphasis on sodium iodide symporter (NIS). Apart from its natural expression in thyroid, NIS protein expression has raised the possibility of using radioiodide therapy and diagnosis in few non-thyroidal cancers as well. In this review, we also covered various challenges to get NIS gene therapeutics from bench to bedside in various non-thyroidal cancers.

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