Background: Ovarian cancer is the most lethal gynecologic malignancy. There is a lack of comprehensive investigation of disease initiation and progression, including gene expression changes during early metastatic colonization. Methods: RNA-sequencing (RNA-seq) was done with matched primary tumors and fallopian tubes (n = 8 pairs) as well as matched metastatic and primary tumors (n = 11 pairs) from ovarian cancer patients. Since these are end point analyses, it was combined with RNA-seq using high-grade serous ovarian cancer cells seeded on an organotypic three-dimensional (3D) culture model of the omentum, mimicking early metastasis. This comprehensive approach revealed key changes in gene expression occurring in ovarian cancer initiation and metastasis, including early metastatic colonization. Results: 2987 genes were significantly deregulated in primary tumors compared to fallopian tubes, 845 genes were differentially expressed in metastasis compared to primary tumors and 304 genes were common to both. An assessment of patient metastasis and 3D omental culture model of early metastatic colonization revealed 144 common genes that were altered during early colonization and remain deregulated even in the fully developed metastasis. Deregulation of the matrisome was a key process in early and late metastasis. Conclusion: These findings will help in understanding the key pathways involved in ovarian cancer progression and eventually targeting those pathways for therapeutic interventions.

The trypanosomatid parasites continue their killing spree resulting in significant annual mortality due to the lack of effective treatments and the prominence of these diseases in poorer countries. These dimorphic parasites thrive unchecked in the host system, outsmarting the immune mechanisms. An understanding of biology of these parasitic forms will help in the management and elimination of these fatal diseases. Investigation of various metabolic pathways in these parasites has shed light in the understanding of the unique biology of the trypansomatids. An understanding of these pathways have helped in tracing the soft targets in the metabolic pathways, which could be used as effective drug targets which would further impact the therupeutic implications. Pyrimidine pathway is a vital metabolic pathway which yields in the formation of pyrimidines, which are then integrated in nucleic acids (DNA and RNA) in sugars (UDP sugars) and lipids (CDP lipids). A wealth of data and information has been generated in the past decades by in-depth analyses of pyrimidine pathway in the trypanosomatid parasites, which can aid in the identification of anomalies between the parasitic and host counterpart which could be further harnessed to develop therapeutic interventions for the treatment of parasitic diseases. This review presents an updated and comprehensive detailing of the pyrimidine metabolism in the trypansomatids, their uniqueness and their distinctions, and its possible outcomes that would aid in the eradication of these parasitic diseases.

Apoptosis, a form of programmed cell death, plays a very crucial role in various physiological processes for maintaining cell homeostasis. This process has several characteristic features like membrane blebbing, nuclear condensation, DNA fragmentation and cell shrinkage. Any defect in this highly regulated process eventually leads to extended cell survival and could result in neoplastic cell expansion followed by genetic instability. The apoptotic machinery is mainly processed and regulated by various caspases, a family of cysteine proteases. Significant advancement has been made towards understanding the molecular mechanisms of apoptosis which provides new insights in modulating the life or death of a cell. The main goal of this review is to highlight recent updates on apoptosis, the cross-talk with other cellular death processes and its therapeutic potentials.

We investigate the role of methionine aminopeptidase 2 (MAP2) in miltefosine induced programmed cell death (PCD) in promastigote form of L. donovani. We report that TNP-470, an inhibitor of MAP2, inhibits programmed cell death in miltefosine treated promastigotes. It inhibits the biochemical features of metazoan apoptosis, including caspase3/7 protease like activity, oligonucleosomal DNA fragmentation, collapse of mitochondrial transmembrane potential, and increase in cytosolic pool of calcium ions but did not prevent the cell death and phosphatidyl serine externalization. The data suggests that the MAP2 is involved in the regulation of PCD in parasite. Moreover, TNP-470 shows the leishmanicidal activity (IC50 = 15 µM) and in vitro inhibition of LdMAP2 activity (K i = 13.5 nM). Further studies on MAP2 and identification of death signaling pathways provide valuable information that could be exploited to understand the role of non caspase proteases in PCD of L. donovani.

As far as microbial world concerned on earth, there are large number of domains has shown the potential for various applications. Fungal domain is one of them. Since the discovery of penicillin, various fungi has been harnessed for a large number of applications. Still there is a requirement of novel products for human welfare and development. So what are the fungi of next door? Are the fungal endophytes? Yes? This is the area untouched for a longer period of time. These fungi represent one of the most understudied and diverse group of organisms, are ubiquitous and occur within almost all the plants, including a broad range of hosts in various ecosystems, and therefore play an important role in the natural environment. Despite extensive work in this field, the products of these fungi remains poorly characterized. A large number of endophytic fungi such as Taxomyces, Pestalotiopsis, Muscodor, Piriformospora, Alternaria, Colletotrichum, Cryptosporiopsis, produce enormous valuable products for medicinal, agricultural and industrial importance. Some of the well-known products are taxol (Paclitaxel), serine hydrolases for polyurethane degradation, Annulene (Volatile organic compounds), Colletotric acid and Cryptocandin. So what next, are endophytic fungal metabolites are the future products? The present review explore the potential of these endophytic fungi with respect to the production of various novel secondary metabolites/products in comparison with the traditional fungi of importance.Petrini reported that these microorganisms colonize in healthy tissues of plants, at least for a part of their life cycle, without causing Biodiversity, Bioprospecting and DevelopmentTiwari, J Biodivers Biopros Dev 2015, 2:1 http://dx.