Management of triple-negative breast cancer by natural compounds through different mechanistic pathways.

Triple-negative breast cancer (TNBC) is the most severe form of breast cancer, characterized by the loss of estrogen, progesterone, and human epidermal growth factor receptors. It is caused by various genetic and epigenetic factors, resulting in poor prognosis. Epigenetic changes, such as DNA methylation and histone modification, are the leading mechanisms responsible for TNBC progression and metastasis. This review comprehensively covers the various subtypes of TNBC and their epigenetic causes. In addition, the genetic association of TNBC with all significant genes and signaling pathways linked to the progression of this form of cancer has been enlisted. Furthermore, the possible uses of natural compounds through different mechanistic pathways have also been discussed in detail for the successful management of TNBC.

Cartilage-Specific Cre Recombinase Transgenes/Alleles in the Mouse.

Cartilage is a specialized skeletal tissue with a unique extracellular matrix elaborated by its resident cells, chondrocytes. The tissue presents in several forms, including growth plate and articular cartilage, wherein chondrocytes follow a differential differentiation program and have different fates. The induction of gene modifications in cartilage specifically relies on mouse transgenes and knockin alleles taking advantages of transcriptional elements primarily active in chondrocytes at a specific differentiation stage or in a specific cartilage type. These transgenes/alleles have been widely used to study the roles of specific genes in cartilage development, adult homeostasis, and pathology. As cartilage formation is critical for postnatal life, the inactivation or significant alteration of key cartilaginous genes is often neonatally lethal and therefore hampers postnatal studies. Gold standard approaches to induce postnatal chondrocyte-specific gene modifications include the Cre-loxP and Tet-ON/OFF systems. Selecting the appropriate promoter/enhancer sequences to drive Cre expression is of crucial importance and determines the specificity of conditional gain- or loss-of-function models. In this chapter, we discuss a series of transgenes and knockin alleles that have been developed for gene manipulation in cartilage and we compare their expression patterns and efficiencies.