Per- and polyfluorinated substances (PFAS) promote osteoclastogenesis and bone loss through PPARα activation.

Per- and polyfluoroalkyl substances (PFAS) are emerging as significant environmental contaminants affecting bone health, with studies linking their exposure to decreased bone mineral density (BMD), enhanced osteoclastogenesis, and disruptions in the bone marrow microenvironment. While current research highlights the effects on bone and BMD, there is a critical gap in understanding the mechanisms behind these effects. Studies presented here investigate the effects of legacy and alternative PFAS, particularly hexafluoropropylene oxide dimer acid (GenX) and perfluorohexane sulfonic acid (PFHxS), on bone health using and models.

Targeting SCD in SCD-amplified prostate cancer inhibits growth in bone by modulating cellular stress, mTOR, and DNA damage pathways.

The bone microenvironment is abundant in adipocytes and fosters metastatic progression, but the underlying mechanisms are not fully understood. We hypothesize that Stearoyl-Coenzyme A Desaturase (SCD) acts as a tumor-promoting enzyme by modulating cellular stress to support the growth and survival of prostate cancer (PCa) in bone. We observe that SCD-amplified PCa cells are highly sensitive to SCD loss and show reduced PCa spheroid size, diminished mTOR signaling, and increased ER stress.

The long-chain polyfluorinated alkyl substance perfluorohexane sulfonate (PFHxS) promotes bone marrow adipogenesis.

Per- and polyfluoroalkyl substances (PFAS) bioaccumulate in different organ systems, including bone. While existing research highlights the adverse impact of PFAS on bone density, a critical gap remains in understanding the specific effects on the bone marrow microenvironment, especially the bone marrow adipose tissue (BMAT). Changes in BMAT have been linked to various health consequences, such as the development of osteoporosis and the progression of metastatic tumors in bone.

Ru(II)-Photoactive Agents for Targeting ER Stress and Immunogenic Cell Death.

Immunotherapy has emerged as a promising avenue for cancer treatment by bolstering the immune system's ability to recognize and attack cancer cells. Photodynamic therapy shows potential in enhancing antitumor immunity, though the mechanisms behind its success are not fully understood. In this manuscript, we investigate two previously reported green light activated PCT/PDT agents where compound - [Ru(tpy)(Me2bpy)( )] , (tpy = 2,2':6',2''- terpyridine, Me2bpy = 6,6'-dimethyl-2,2'-bipyridine, = pyridyl-BODIPY-I2,) - shows remarkable photoselectivity in assays containing both 2D cancer cells and 3D cocultures containing BALB/c macrophages and 4T1 murine breast cancer cells.

Adipocyte-driven unfolded protein response is a shared transcriptomic signature of metastatic prostate carcinoma cells.

A critical unknown in the field of skeletal metastases is how cancer cells find a way to thrive under harsh conditions, as exemplified by metastatic colonization of adipocyte-rich bone marrow by prostate carcinoma cells. To begin understanding molecular processes that enable tumor cells to survive and progress in difficult microenvironments such as bone, we performed unbiased examination of the transcriptome of two different prostate cancer cell lines in the absence or presence of bone marrow adipocytes. Our RNAseq analyses and subsequent quantitative PCR and protein-based assays reveal that upregulation of endoplasmic reticulum (ER) stress and unfolded protein response (UPR) genes is a shared signature between metastatic prostate carcinoma cell lines of different origin.