A chemically adjustable BMP6-IL6 axis in mesenchymal stem cells drives acute myeloid leukemia cell differentiation.

Chemotherapy alone or in combination with allogeneic stem cell transplantation has been the standard of care for acute myeloid leukemia (AML) for decades. Leukemia relapse with limited treatment options remains the main cause of treatment failure. Therefore, an effective and safe approach to improve treatment outcomes is urgently needed for most AML patients.

A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy.

Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects.

Blockage of PPARγ T166 phosphorylation enhances the inducibility of beige adipocytes and improves metabolic dysfunctions.

Beige adipocytes in mammalian white adipose tissue (WAT) can reinforce fat catabolism and energy expenditure. Promoting beige adipocyte biogenesis is a tantalizing tactic for combating obesity and its associated metabolic disorders. Here, we report that a previously unidentified phosphorylation pattern (Thr166) in the DNA-binding domain of PPARγ regulates the inducibility of beige adipocytes.

PFKFB4 facilitates palbociclib resistance in oestrogen receptor-positive breast cancer by enhancing stemness.

Background: ER breast cancer (ER BC) is the most common subtype of BC. Recently, CDK4/6 inhibitors combined with aromatase inhibitors have been approved by FDA as the first-line therapy for patients with ER BC, and showed promising therapeutic efficacy in clinical treatment. However, resistance to CDK4/6 inhibitors is frequently observed.

Pretreatment of umbilical cord derived MSCs with IFN-γ and TNF-α enhances the tumor-suppressive effect on acute myeloid leukemia.

Currently, the standard therapeutic approach of AML consists of chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). However, these strategies are usually associated with adverse side effects and high risk of relapse following HSCT. Thus, it is imperative to find an alternative way against AML progression.

Establishment of a novel mesenchymal stem cell-based regimen for chronic myeloid leukemia differentiation therapy.

Chronic myeloid leukemia (CML) is characterized by the accumulation of malignant and immature white blood cells which spread to the peripheral blood and other tissues/organs. Despite the fact that current tyrosine kinase inhibitors (TKIs) are capable of achieving the complete remission by reducing the tumor burden, severe adverse effects often occur in CML patients treated with TKIs. The differentiation therapy exhibits therapeutic potential to improve cure rates in leukemia, as evidenced by the striking success of all-trans-retinoic acid in acute promyelocytic leukemia treatment.

Increased release of microvesicles containing mitochondria is associated with the myeloid differentiation of AML-M5 leukaemia cells.

Extensive literature has demonstrated that acute myeloid leukaemia (AML) cells show enhanced mitochondrial biogenesis and increased reliance on oxidative phosphorylation (OXPHOS) compared with normal hematopoietic progenitors, and one hallmark of AML leukaemia blasts is myeloid differentiation blockade. However, relatively few reports have linked these processes. Recent studies have indicated that therapies that overcome differentiation arrest represent an effective treatment strategy.

Insights into the mechanism of how Morin suppresses amyloid fibrillation of hen egg white lysozyme.

This communication describes the inhibitory effect of Morin on the fibrillation of Hen Egg White Lysozyme (HEWL), a generic amyloid-forming model protein. This effect was dose-dependent and stronger than other small molecules we have tested previously. Spectrofluorometric and computational studies support a model suggesting that Morin inhibits amyloid fibril formation of HEWL by binding to the aggregation prone cleft region of the β-domain of HEWL, thereby stabilizing the molecule in its native-like state.