Regulation of Kisspeptin mediated signaling by non-coding RNAs in different cancers: the beginning of a new era.

Kisspeptin-driven intracellular signaling has captured enormous attention because of its central role in cancer onset and progression. Wealth of information has helped us to develop a better understanding of the critical roles of Kisspeptin-mediated signaling in different cancers. However, astonishingly, we have not yet drilled down deep into the mysterious aspects associated with non-coding RNA mediated regulation of Kisspeptin-driven signaling. Therefore, in this mini-review, we will comprehensively analyze available evidence related to miRNAs and long non-coding RNAs (LncRNAs) and their ability to modulate Kisspeptin-mediated signaling. There are visible knowledge gaps about interplay between non-coding RNAs and Kisspeptin-mediated signaling. It will be appropriate to say that we have just started to scratch the surface of an entirely new regulatory layer of Kisspeptin-mediated transduction cascade. Mechanistically, it has been revealed that inhibition of Kisspeptin mediated signaling activated and stimulated the entry of NFκB into the nucleus to stimulate expression of proteins which can sequentially inactivate tumor suppressor miRNAs. miRNAs have also an instrumental role in regulation of proteins which post-translationally modify and inhibit KISS1 expression. It is becoming progressively more understandable that LncRNAs act as miRNA sponges and protect oncogenic mRNAs. However, these facets are also incompletely investigated. Identification of LncRNAs which interfere with Kisspeptin-mediated pathway either through acting as miRNA sponges or working with methylation-associated machinery will be helpful in sharpening the resolution of the pixels of the regulatory network which shapes Kisspeptin-mediated signaling.

Zinc silicate mineral-coated scaffold improved in vitro osteogenic differentiation of equine adipose-derived mesenchymal stem cells.

In current study we aimed to coat the PLLA scaffold with zinc (Zn) silicate mineral nanoparticles. Then, using equine adipose-derived stem cells (ASCs) we intended to compare the osteogenic induction potency of Zn silicate mineral-coated PLLA scaffold with uncoated PLLA scaffold and tissue culture plastic (TCPS). Adipose tissues were collected from 3 horses, and isolation of ASCs was achieved by enzymatic digestion. PLLA scaffold was successfully prepared using a phase separation method and coated with Zn silicate mineral nanoparticles. The coating efficiency was then characterized by scanning electron microscopy and further evaluated with the application of fourier transform infrared microscopic imaging. Viability and growth characteristics of ASCs on TCPS, uncoated and coated PLAA scaffolds were investigated by MTT assay. Alizarin Red staining was performed for determination of calcium deposition following the osteogenic induction. Furthermore, other common osteogenic markers such as alkaline phosphatase (ALP) activity, calcium content, as well as osteogenic (Runx2, ALP, osteonectin, and collagen I) marker genes were also evaluated. Our data showed that Zn silicate mineral nanoparticles was coated successfully on PLLA scaffold and such scaffold had no detrimental effect on cell growth rate as indicated by MTT assay. Moreover, ASCs that differentiated on Zn silicate mineral-coated PLLA scaffold indicated higher ALP activity, more calcium content, and higher expression of bone-related genes than that on uncoated PLLA scaffold and TCPS. Adequate proliferation rate and higher expression of osteogenic markers of stem cells, provides this scaffold as a suitable substrate to support proliferation and differentiation of ASCs in equine.