Four newly synthesized enones induce mitochondrial-mediated apoptosis and G2/M cell cycle arrest in colorectal and cervical cancer cells.

Over the last few decades, we have gained insight into how researchers attempted to modify some natural molecules to be utilized as prospective agents for cancer treatment. Many scientists synthesized new natural compounds by incorporating specific functional groups and metals that improved their antitumor activity while reducing undesirable side effects. In this investigation, we synthesized four novel structurally modified enones that differ in the functional groups attached to the carbonyl group of the enone system (methyl - E1; isopropyl - E2; isobutyl - E3; and cyclopropyl - E4) and explored their anticancer potential against human carcinoma of the colon HCT-116, the cervical HeLa, and normal lung cells MRC-5.

tsCRISPR based identification of Rab proteins required for the recycling of TRPL ion channel.

In polarized cells, the precise regulation of protein transport to and from the plasma membrane is crucial to maintain cellular function. Dysregulation of intracellular protein transport in neurons can lead to neurodegenerative diseases such as Retinitis Pigmentosa, Alzheimer's and Parkinson's disease. Here we used the light-dependent transport of the TRPL (transient receptor potential-like) ion channel in photoreceptor cells to study the role of Rab proteins in TRPL recycling.

The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity.

Immune checkpoint blockade is effective for some patients with cancer, but most are refractory to current immunotherapies and new approaches are needed to overcome resistance. The protein tyrosine phosphatases PTPN2 and PTPN1 are central regulators of inflammation, and their genetic deletion in either tumour cells or immune cells promotes anti-tumour immunity. However, phosphatases are challenging drug targets; in particular, the active site has been considered undruggable.

Toll-like receptor-3 contributes to the development of aortic valve stenosis.

Aortic valve stenosis (AS) development is driven by distinct molecular and cellular mechanisms which include inflammatory pathways. Toll-like-receptor-3 (TLR3) is a lysosomal pattern-recognition receptor that binds double-stranded RNA and promotes pro-inflammatory cellular responses. In recent years, TLR3 has emerged as a major regulator of vascular inflammation.

Activation of neutral sphingomyelinase 2 through hyperglycemia contributes to endothelial apoptosis via vesicle-bound intercellular transfer of ceramides.

Background: Pro-apoptotic and pro-inflammatory ceramides are crucially involved in atherosclerotic plaque development. Local cellular ceramide accumulation mediates endothelial apoptosis, especially in type 2 diabetes mellitus, which is a major cardiovascular risk factor. In recent years, large extracellular vesicles (lEVs) have been identified as an important means of intercellular communication and as regulators of cardiovascular health and disease.