Advances in understanding disease pathogenesis correlates to modifications in gene expression within different tissues and organ systems. In depth knowledge about the dysregulation of gene expression profiles is fundamental to fully uncover mechanisms in disease development and changes in host homeostasis. The body of knowledge surrounding mammalian regulatory elements, specifically regulators of chromatin structure, transcriptional and translational activation, has considerably surged within the past decade. A set of key regulators whose function still needs to be fully elucidated are small non-coding RNAs (sncRNAs). Due to their broad range of unfolding functions in the regulation of gene expression during transcription and translation, sncRNAs are becoming vital to many cellular processes. Within the past decade, a novel class of sncRNAs called PIWI-interacting RNAs (piRNAs) have been implicated in various diseases, and understanding their complete function is of vital importance. Historically, piRNAs have been shown to be indispensable in germline integrity and stem cell development. Accumulating research evidence continue to reveal the many arms of piRNA function. Although piRNA function and biogenesis has been extensively studied in Drosophila, it is thought that they play similar roles in vertebrate species, including humans. Compounding evidence suggests that piRNAs encompass a wider functional range than small interfering RNAs (siRNAs) and microRNAs (miRNAs), which have been studied more in terms of cellular homeostasis and disease. This review aims to summarize contemporary knowledge regarding biogenesis, and homeostatic function of piRNAs and their emerging roles in the development of pathologies related to cardiomyopathies, cancer, and infectious diseases.

A novel class of gallic acid based glycoconjugates were designed and synthesized as potential anticancer agents. Among all the compounds screened, compound 2a showed potent anticancer activity against breast cancer cells. The latter resulted in tubulin polymerization inhibition and induced G2/M cell cycle arrest, generation of reactive oxygen species, mitochondrial depolarization and subsequent apoptosis in breast cancer cells. In addition, ultraviolet-visible spectroscopy and fluorescence quenching studies of the compound with tubulin confirmed direct interaction of compounds with tubulin. Molecular modeling studies revealed that it binds at the colchicine binding site in tubulin. Further, 2a also exhibited potent in vivo anticancer activity in LA-7 syngeneic rat mammary tumor model. Current data projects its strong candidature to be developed as anticancer agent.

A series of biologically important 6-(imidazo[1,2-a]pyridin-2-yl)-2H-chromen-2-one derivatives were synthesized by employing the silver(I) catalysed Groebke–Blackburn–Bienayme multicomponent reaction. The synthesized compounds were tested in a primary calvarial osteoblast cells by alkaline phosphatase assay and an alizarin red-S staining assay for their possible osteoprotective properties. Further, the effects of active compounds 6h, 6l, and 6o on the expression of osteogenic genes BMP2, RUNX2, COL1, and OCN were measured by qPCR. Out of three promising compounds, 6l and 6o significantly induced apoptosis in MDA-MB-231 cancer cells via mitochondrial depolarisation without affecting normal cells. In an in vitro co-culture model of bone metastasis, we investigated the ability of coumarin–imidazo[1,2-a]pyridine hybrids to reverse the negative impact of MDA-MB-231 cancer cells on osteoblast differentiation. The results illustrate the potential of designed hybrids to re-establish the bone homeostasis. These findings demonstrate the significance of newly synthesized hybrids as lead molecules, possessing both antiosteoporotic and anticancer properties that can be developed into new therapeutic agents to alleviate osteoporosis and bone metastasis.