Necroptosis inhibitors: mechanisms of action and therapeutic potential.

Necroptosis is a type of programmed cell death that is morphologically similar to necrosis. This type of cell death is involved in various pathophysiological disorders, including inflammatory, neurodegenerative, infectious, and malignant diseases. Receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL) pseudokinase constitute the core components of the necroptosis signaling pathway and are considered the most promising targets for therapeutic intervention. The discovery and characterization of necroptosis inhibitors not only accelerate our understanding of the necroptosis signaling pathway but also provide important drug candidates for the treatment of necroptosis-related diseases. Here, we will review recent research progress on necroptosis inhibitors, mechanisms of action and their potential applications for disease treatment.

Bioreduction (AuIII to Au0) and stabilization of gold nanocatalyst using Kappa carrageenan for degradation of azo dyes.

Colloidal gold nanoparticles (AuNPs) have been used in high technology applications due to their optical and electronic properties. Unfortunately, these broader applications are severely hampered by their agglomeration tendency and instability. Therefore, in this study, highly stable and aggregation resistant AuNPs were synthesized using Kappa carrageenan (κ-car) media (as a reducing and stabilizing agent) by a green synthesis protocol. The effect of different factors of reaction such as the concentration of κ-car (Cκ-car %), reaction time (t), temperature (T), and solution pH (here after simply define to 'reaction parameters') was studied by one-variable-at-a-time technique to optimize the yield production of AuNPs. The characterization of AuNPs synthesized at optimum conditions revealed that the particles are spherical in shapes, smaller in size (13.5 ± 5.1 nm) with a narrow distribution, highly crystalline (d-spacing = 0.230 nm) in nature, well stabilized (zeta potential = -22.1 mV) by coating by a thin layer of κ-car carbohydrate. The synthesized AuNPs reveal excellent catalytic function in the degradation (up to 99%) of azo-dyes. The kinetics study in the degradation reaction revealed that the technique could be extended to real wastewater treatment applications.

miR­342­5p promotes Zmpste24­deficient mouse embryonic fibroblasts proliferation by suppressing GAS2.

Cellular senescence is an irreversible growth arrest of cells that maintain their metabolic activities. Premature senescence can be induced by different stress factors and occurs in mouse embryonic fibroblasts (MEFs) derived from Zmpste24 metalloproteinase­deficient mice, a progeria mouse model of Hutchinson­Gilford Progeria Syndrome. Previous studies have shown that miR­342­5p, an intronic microRNA (miRNA/miR) reportedly involved in ageing associated diseases, is downregulated in Zmpste24­/­ MEFs. However, whether miR­342­5p is associated with the premature senescence phenotype of Zmpste24­/­ MEFs remains unclear. Thus, the present study investigated the effects of miR­342­5p on cellular senescence and cell proliferation in Zmpste24­/­ MEFs. The results showed that miR­342­5p overexpression ameliorated the cellular senescence phenotype to a certain extent, promoted cell proliferation and increased the G2+M cell cycle phase in Zmpste24­/­ MEFs. Nonetheless, it was difficult to observe the opposite cell phenotypes in wild­type (WT) MEFs transfected with the miR­342­5p inhibitor. Growth­arrest­specific 2 (GAS2) was identified as a target gene of miR­342­5p in Zmpste24­/­ MEFs. In addition, miR­342­5p was identified to be downregulated in WT MEFs during replicative senescence, while Gas2 was upregulated. Taken together, these findings suggest that downregulated miR­342­5p is involved in regulating cell proliferation and cell cycles in Zmpste24­/­ MEFs by suppressing GAS2 in vitro.