Riggs Honeycutt (shirtbaker1)
Hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a key enzyme in the mevalonate pathway of cholesterol synthesis. Dysregulation of HMGCS1 expression is a common occurrence in many solid tumors. It was also found to be overexpressed in newly diagnosed (ND) and relapsed/refractory (RR) acute myeloid leukemia (AML) patients. Previous study proved that HMGCS1 could induce drug-resistance in AML cells. However, the underlying mechanism how HMGCS1 contributed to chemoresistance remains elusive. Here, we confirmed that HMGCS1 inhibitor Hymeglusin enhanced cytarabine/Adriamycin (Ara-c/ADR) chemo-sensitivity in AML cells lines. Moreover, Ara-c-resistant HL-60 cells (HL-60/Ara-c) and ADR-resistant HL-60 cells (HL-60/ADR) were more sensitive to HMGCS1 inhibition than HL-60 cells. In addition, we demonstrated that the transcription factor GATA1 was the upstream regulator of HMGCS1 and could directly bind to the HMGCS1 promoter. After treatment of Tunicamycin (Tm), the number of mitochondria was increased and the damage of endoplasmic reticulum (ER) was reduced in bone marrow cells from AML-RR patients, compared to cells from AML-CR group. HMGCS1 protected mitochondria and ER under ER stress and up-regulated unfold protein response (UPR) downstream molecules in AML cells. In summary, we proved that HMGCS1 could upregulate UPR downstream components, protect mitochondria and ER from damage in AML cells under stress, therefore conferring drug resistance. Therefore, HMGCS1 could serve as a novel target for treatment of patients with intolerant chemotherapy and AML-RR patients.With the continuous breakthroughs in molecular biology and biochemistry, we have constantly made great progress in the treatment of lung cancer. There is no doubt that standard treatment (such as surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy) has greatly improved the prognosis of lung cancer populations. In particular, the immunotherapy has brought more and more good news to countless lung cancer patients. In contrast to these standard treatments, traditional Chinese medicine (TCM) rarely has a profound and comprehensive overview in the field of lung cancer. This article will summarize the latest progress of TCM in lung cancer which is mainly non-small cell lung cancer (NSCLC) from theory to clinical practice, which would carry forward the sophisticated TCM and promote the development of modern medicine.Iron is an essential trace element in the metabolism of almost all living organisms. Iron overload can disrupt bone homeostasis by significant inhibition of osteogenic differentiation and stimulation of osteoclastogenesis, consequently leading to osteoporosis. Iron accumulation is also involved in the osteoporosis induced by multiple factors, such as estrogen deficiency, ionizing radiation, and mechanical unloading. Iron chelators are first developed for treating iron overloaded disorders. However, growing evidence suggests that iron chelators can be potentially used for the treatment of bone loss. In this review, we focus on the therapeutic effects of iron chelators on bone loss. Iron chelators have therapeutic effects not only on iron overload induced osteoporosis, but also on osteoporosis induced by estrogen deficiency, ionizing radiation, and mechanical unloading, and in Alzheimer's disease-associated osteoporotic deficits. Iron chelators differently affect the cellular behaviors of bone cells. For osteoblast lineage cells (bone mesenchymal stem cells and osteoblasts), iron chelation stimulates osteogenic differentiation. Conversely, iron chelation significantly inhibits osteoclast differentiation. These different responses may be associated with the different needs of iron during differentiation. Fibroblast growth factor 23, angiogenesis, and antioxidant capability are also involved in the osteoprotective effects of iron chelators.Neurodegenerative diseases (NDs) represent a common neurological pathology that determines a progressive de
