T1 and 1065 DEGs (897 up, 168 down) at T3 vs. T1 in the group of women (n = 11) not using any hormonal contraceptives during the study. There was no response at T2 vs. T1 and a small number of DEGs, 260 (214 up, 46 down) at T3 vs. T1 in the group of 14 women using contraceptives. In summary, r-hCG has a remarkable effect on the gene expression profile of breast tissues from BRCA1/2 carriers who did not use any contraception. This opens an opportunity for a novel preventive strategy to reduce the incidence of breast cancer.In summary, r-hCG has a remarkable effect on the gene expression profile of breast tissues from BRCA1/2 carriers who did not use any contraception. This opens an opportunity for a novel preventive strategy to reduce the incidence of breast cancer.Flavonoids, a broad class of polyphenolic compounds, can potentially have several therapeutic properties in human diseases, including protective effects against oxidative stress, inflammation, cardiovascular disease, diabetes, neurodegenerative disorders, and cancers. BP-1-102 Luteolin as a member of flavonoids has been found to exhibit several anticancer properties mainly through cell apoptosis induction, inhibition of invasion, cell proliferation, network formation, and migration. Recent studies have revealed that phytochemicals such as luteolin may exert therapeutic properties through microRNAs (miRNAs or miRs), which have been emerged as important molecules in cancer biology in recent years. miRNAs, as a class of noncoding RNAs, have several important roles in cancer progression or regression. In this review, we aimed to summarize and discuss the role of miRNAs in the luteolin effects on different cancers. This review can be in line with the studies, which have shown that miRNAs may be potential therapeutic targets in cancer treatment. Despite attention to racial disparities in outcomes for heart failure (HF) and other chronic diseases, progress against these inequities has been gradual at best. The disparities of COVID-19 and police brutality have highlighted the pervasiveness of systemic racism in health outcomes. Whether racial bias impacts patient access to advanced HF therapies is unclear. As documented in other settings, racial bias appears to operate in HF providers' consideration of patients for advanced therapy. Multiple medical and psychosocial elements of the evaluation process are particularly vulnerable to bias. Reducing gaps in access to advanced therapies will require commitments at multiple levels to reduce barriers to healthcare access, standardize clinical operations, research the determinants of patient success and increase diversity among providers and researchers. Progress is achievable but likely requires as disruptive and investment of immense resources as in the battle against COVID-19.Reducing gaps in access to advanced therapies will require commitments at multiple levels to reduce barriers to healthcare access, standardize clinical operations, research the determinants of patient success and increase diversity among providers and researchers. Progress is achievable but likely requires as disruptive and investment of immense resources as in the battle against COVID-19.Many solid cancers metastasize to the bone and bone marrow (BM). This process may occur even before the diagnosis of primary tumors, as evidenced by the discovery of disseminated tumor cells (DTCs) in patients without occult malignancies. The cellular fates and metastatic progression of DTCs are determined by complicated interactions between cancer cells and BM niches. Not surprisingly, these niches also play important roles in normal biology, including homeostasis and turnover of skeletal and hematopoiesis systems. In this Review, we summarize recent findings on functions of BM niches in bone metastasis (BoMet), particularly during the early stage of colonization. In light of the rich knowledge of hematopoiesis and osteogenesis, we highlight how DTCs may progress into overt BoMet by taking advantage of niche cells and their activities in tissue turnover, especially those related to immunomodulation and bone repair.Glioblastoma (GBM) is composed of heterogeneous tumor cell populations, including those with stem cell properties, termed glioma stem cells (GSCs). GSCs are innately less radiation sensitive than the tumor bulk and are believed to drive GBM formation and recurrence after repeated irradiation. However, it is unclear how GSCs adapt to escape the toxicity of repeated irradiation used in clinical practice. To identify important mediators of adaptive radioresistance in GBM, we generated radioresistant human and mouse GSCs by exposing them to repeat cycles of irradiation. Surviving subpopulations acquired strong radioresistance in vivo, which was accompanied by a reduction in cell proliferation and an increase in cell-cell adhesion and N-cadherin expression. Increasing N-cadherin expression rendered parental GSCs radioresistant, reduced their proliferation, and increased their stemness and intercellular adhesive properties. Conversely, radioresistant GSCs lost their acquired phenotypes upon CRISPR/Cas9-mediated knockout of N-cadherin. Mechanistically, elevated N-cadherin expression resulted in the accumulation of β-catenin at the cell surface, which suppressed Wnt/β-catenin proliferative signaling, reduced neural differentiation, and protected against apoptosis through Clusterin secretion. N-cadherin upregulation was induced by radiation-induced IGF1 secretion, and the radiation resistance phenotype could be reverted with picropodophyllin, a clinically applicable blood-brain-barrier permeable IGF1 receptor inhibitor, supporting clinical translation.Nonalcoholic fatty liver disease (NAFLD) results in the accumulation of fat in the liver and can progress as an inflammatory disorder with considerable vascular endothelial dysfunction known as nonalcoholic steatohepatitis (NASH). Inflammatory signals can trigger the expression of vascular cell adhesion molecule 1 (VCAM-1) on endothelial cells. VCAM-1 is a surface protein that induces adherence and extravasation of monocytes to blood vessels. In this issue of the JCI, Furuta et al. report on their sequencing of RNA transcripts from the livers of mice fed a NASH-inducing diet. VCAM-1 was upregulated in the whole liver as well as liver sinusoidal endothelial cells (LSECs). When the researchers incubated LSECs with palmitate, a toxic lipid, VCAM-1 was upregulated. Notably, inhibiting VCAM-1 in the NASH model reduced VCAM-1 expression, lessened infiltrating macrophages, and mitigated fibrosis. This study connects steatosis to endothelial dysfunction and inflammation and suggests that targeting VCAM-1 may address fibrosis in patients with NASH.