Foxc2, a member of the winged helix transcription factor family, is essential for eye, calvarial bone, cardiovascular and kidney development in mice. Nevertheless, how Foxc2-expressing cells and their descendent cells contribute to the development of these tissues and organs has not been elucidated. Here, we generated a Foxc2 knock-in (Foxc2 ) mouse, in which administration of estrogen receptor antagonist tamoxifen induces nuclear translocation of Cre recombinase in Foxc2-expressing cells. By crossing with ROSA-LacZ reporter mice (Foxc2 ; R26R), the fate of Foxc2 positive (Foxc2 ) cells was analyzed through LacZ staining at various embryonic stages. We found Foxc2 cell descendants in the supraoccipital and exoccipital bone in E18.5 embryos, when tamoxifen was administered at embryonic day (E) 8.5. Furthermore, Foxc2 descendant cranial neural crest cells at E8-10 were restricted to the corneal mesenchyme, while Foxc2 cell derived cardiac neural crest cells at E6-12 were found in the aorta, pulmonary trunk and valves, and endocardial cushions. Foxc2 cell descendant contributions to the glomerular podocytes in the kidney were also observed following E6.5 tamoxifen treatment. Our results are consistent with previous reports of Foxc2 expression during early embryogenesis and the Foxc2 mouse provides a tool to investigate spatiotemporal roles of Foxc2 and contributions of Foxc2 expressing cells during mouse embryogenesis.

Dengue fever is a viral infection caused by Aedes mosquitoes that has recently expanded fast in many of the WHO member states globally. Female mosquitoes, mostly Aedes aegypti and, to a smaller degree, Aedes albopictus, disseminate dengue virus. Dengue fever has been more common in recent decades all across the world, and Bangladesh is no exception. As the COVID-19 outbreak wreaks havoc, the following rise in dengue illnesses has been a source of considerable concern. As the health care has been stretched thin in these dangerous times, the vulnerable population has been left at the mercy of these two viral infections. Lack of knowledge, major legislative changes, poor eradication initiatives, and a lack of financing resources have all contributed to the increase in numbers. Stakeholders and policymakers must begin taking meaningful actions and implementing well-thought-out adjustments immediately, or the situation will worsen, resulting in the loss of thousands of innocent lives.

The forkhead box C2 (Foxc2) protein is a member of the forkhead/winged helix transcription factor family and plays an essential role in cardiovascular development. Previous studies showed that Foxc2 null mouse embryos die during midgestation or just after birth with severe cardiovascular defects, including interruption, coarctation of the aortic arch and ventricular septal defects. These are also seen in human congenital heart disease. However, the tissue specific role of Foxc2 in aortic arch remodelling is not yet fully understood. Here we show that Foxc2 is expressed in a restricted pattern in several cell populations, including the mesenchyme and endothelium of pharyngeal arch arteries, which are important for cardiovascular development. In this study, we use a conditional knockout approach to examine the tissue specific role of Foxc2 in aortic arch remodelling. We demonstrate that mouse embryos lacking Foxc2 in Nkx2.5-expressing mesenchyme and endothelium of pharyngeal arch arteries display aortic arch interruption type B and ventricular septal defects. In contrast, conditional deletion of Foxc2 in Tie2-expressing endothelial cells does not result in aortic arch or ventricular septal defects, but does result in embryonic lethality due to peripheral oedema. Our data therefore provide for a detailed understanding of the role of mesenchymal Foxc2 in aortic arch remodelling and in the development of ventricular septum.Human congenital heart defects are the most common birth defect, affecting 9 in 1000 live births (28). Outflow tract defects, aortic arch malformation and ventricular septal defects (VSD) are common forms of human congenital heart disease (14). In vertebrates, the heart is the first organ that develops through a complicated series of morphogenetic events involving the interaction between cells of different embryonic sources (3, 23). The mature aortic arch and great vessels derive from the embryonic pharyngeal arch arteries and the aortic sac. Five pairs of pharyngeal arch arteries appear in a rostrocaudal direction during embryogenesis and form the precursors of the great vessels and large arteries in the head and neck. Arch arteries develop from the aortic sac and end in the dorsal aorta and finally contribute to specific arteries (25). At embryonic day 9.5 (E9.5) in mice, the first and second arch arteries appear. At E10.5, the first and second arch arteries disappear, while the third, fourth and sixth arch arteries appear. All arch arteries undergo a remodelling process to

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Salvicine is a new diterpenoid quinone substance from a natural source, specifically in a Chinese herb. It has powerful growth-controlling abilities against a broad range of human cancer cells in both in vitro and in vivo environments. A significant inhibitory effect of salvicine on multidrug-resistant (MDR) cells has also been discovered. Several research studies have examined the activities of salvicine on topoisomerase II (Topo II) by inducing reactive oxygen species (ROS) signaling. As opposed to the well-known Topo II toxin etoposide, salvicine mostly decreases the catalytic activity with a negligible DNA breakage effect, as revealed by several enzymatic experiments. Interestingly, salvicine dramatically reduces lung metastatic formation in the MDA-MB-435 orthotopic lung cancer cell line. Recent investigations have established that salvicine is a new non-intercalative Topo II toxin by interacting with the ATPase domains, increasing DNA–Topo II interaction, and suppressing DNA relegation and ATP hydrolysis. In addition, investigations have revealed that salvicine-induced ROS play a critical role in the anticancer-mediated signaling pathway, involving Topo II suppression, DNA damage, overcoming multidrug resistance, and tumor cell adhesion suppression, among other things. In the current study, we demonstrate the role of salvicine in regulating the ROS signaling pathway and the DNA damage response (DDR) in suppressing the progression of cancer cells. We depict the mechanism of action of salvicine in suppressing the DNA–Topo II complex through ROS induction along with a brief discussion of the anticancer perspective of salvicine.