Pre-eclampsia (PE) is a pregnancy-specific disorder, characterized by hypertension and proteinuria. In PE, trophoblasts mediated inadequate remodeling of uterine spiral arteries seem to interrupt uteroplacental blood flow, one of the hallmarks in the early onset of PE (EO-PE). This, in turn, results in placental ischemia–reperfusion injury during hypoxia and reoxygenation episodes, leading to the generation of reactive oxygen species (ROS) and oxidative stress (OS). But still it is debatable if OS is a cause or consequence of PE. In this present study, we have investigated the effects of OS on PE placentae and trophoblast cell functions using BeWo and HTR8/SVneo cell lines. PE placental tissues showed abnormal ultrastructure, high level of reactive oxygen species (ROS) with altered unfolded protein responses (UPR) in compare with term placental tissues. Similar to PE placentae, during OS induction, the trophoblast cells showed altered invasion and migration properties with significantly variable expression of differentiation and invasion markers, e.g., syncytin and MMPs. The effect was rescued by antioxidant, N-acetyl cysteine, thereby implying a ROS-specific effect and in the trophoblast cells, OS triggers UPR pathway through IRE1α-XBP1 axis. Taken together, these findings highlight the harmful effect of unfolded protein response, which was induced due to OS on trophoblast cells and deformed invasion and differentiation programme and can be extended further to clinical settings to identify clinically approved antioxidants during pregnancy as a therapeutic measure to reduce the onset of PE.

Pregnancy in humans is a multi-step complex physiological process comprising three discrete events, decidualization, implantation and placentation. Its overall success depends on the incremental advantage that each of the preceding stages passes on to the next. The success of these synchronized sequels of events is an outcome of timely coordination between them. The pregnancy events are coordinated and governed primarily by the ovarian steroid hormones, estrogen and progesterone, which are essentially ligand-activated transcription factors. It’s well known that intercellular signaling of steroid hormones engages a plethora of adapter proteins that participate in executing the biological functions. This involves binding of the hormone receptor complex to the DNA response elements in a sequence specific manner. Working withDrosophila melanogaster, the heat shock proteins (HSPs) were originally described by Ferruccio Ritossa back in the early 1960s. Over the years, there has been considerable advancement of our understanding of these conserved families of proteins, particularly in pregnancy. Accumulating evidence suggests that endometrial and uterine cells have an abundance of HSP27, HSP60, HSP70 and HSP90, implying their possible involvement during the pregnancy process. HSPs have been found to be associated with decidualization, implantation and placentation, with their dysregulation associated with implantation failure, pregnancy loss and other feto-maternal complications. Furthermore, HSP is also associated with stress response, specifically in modulating the ER stress, a critical determinant for reproductive success. Recent advances suggest a therapeutic role of HSPs proteins in improving the pregnancy outcome. In this review, we summarized our latest understanding of the role of different members of the HSP families during pregnancy and associated complications based on experimental and clinical evidences, thereby redefining and exploring their novel function with new perspective, beyond their prototype role as molecular chaperones.

Cancer stem cells (CSCs) constitute a minority cell population characterized by unbounded proliferative potential in both solid and hematological cancers. Despite sharing key stem cell attributes, CSCs possess unique traits, including the initiation and propagation of tumors and resistance to conventional therapies. The purpose of this review is to delve into the origins and fundamental characteristics of CSCs, emphasizing their role in tumor growth and metastasis. The focus extends to unraveling cellular signaling pathways driving oncogenic processes and understanding aberrant cellular crosstalk crucial for targeted cancer therapies. Beginning with an exploration of CSC properties and behavior, we progress to dissecting the cellular signaling network that fuels oncogenic pathways. The discussion spans the inception of CSCs, their survival strategies, and adaptation to new environments. We then transit to recent therapeutic advancements targeting CSCs, culminating in an exploration for precise therapeutic targeting. This review henceforth, underscores the vital significance of comprehending CSCs in cancer progression and treatment resistance. By unraveling the complex signaling pathways and survival mechanisms unique to CSCs, it paves the way for targeted therapeutic strategies that hold immense promise in enhancing cancer treatment efficacy while minimizing collateral damage.