Orai1 calcium channel inhibition prevents progression of chronic pancreatitis.

Patients with recurrent acute pancreatitis (RAP) are at significant risk of developing early chronic pancreatitis (CP), which progresses into irreversible, end-stage CP with severe symptoms. There is no specific therapy in RAP or in early CP that may hinder disease progression. The pathogenesis of CP is complex and involves interactions among multiple cell types, including pancreatic acinar, ductal, and stellate cells (PSC). Therefore, it is pivotal to identify common pathogenic pathways in these cells that could be targeted pharmacologically. The Orai1-mediated store-operated Ca2+ entry (SOCE) is a ubiquitous signaling mechanism that may become overactivated in pathological states resulting in intracellular Ca2+ overload. In this study, we used ex vivo and in vivo preclinical disease models to demonstrate that Orai1 inhibition prevents progression of RAP and early CP. The selective Orai1 inhibitor CM5480 restored the expression of SOCE-associated regulatory factor in acinar cells, prevented uncontrolled Ca2+ elevation, protected acinar and ductal functions, mitigated immune cell infiltration, and diminished PSC activation, proliferation, and migration. We suggest that the overactivation of Orai1 is a crucial pathogenetic event in the progression of early CP and that inhibition of Orai1 could prevent the development of end-stage CP.

Superhydrophobic self-similar nonwoven-titanate nanostructured materials.

HYPOTHESIS: Self-similarity is a scale-invariant irregularity that can assist in designing a robust superhydrophobic material. A combinatorial design strategy involving self-similarity and dual-length scale can be employed to create a new library of a doubly re-entrant, disordered, and porous network of superhydrophobic materials. Asymmetric wettability can be engineered in nonwoven materials by rendering them with superhydrophobic characteristics on one side. EXPERIMENTS: A facile, scalable, and inexpensive spray-coating technique was used to decorate the weakly hydrophobicstearate-treatedtitanate nanowires (TiONWs)over the self-similar nonwoven material. Laser scanning confocal microscopy was employed to image the impalement dynamics in three dimensions. With the aid of X-ray microcomputed tomography analysis, the three-dimensional (3D) nonwoven structural parameters were obtained and analyzed. The underwater superhydrophobic behavior of the prepared samples was investigated. FINDINGS: A classic 'lotus effect' has been successfully endowed in self-similar nonwoven-titanate nanostructured materials (SS-Ti-NMs) from a nonwoven material that housed the air pockets in bulk and water repellent TiONWs on the surface. The finer fiber-based SS-Ti-NMs exhibited lower roll-off angles and a thinner layer of water on its surface. An asymmetric wettability and the unusual display of underwater superhydrophobic behavior of SS-Ti-NMs have been uncovered.

Polyamines treatment during pollen germination and pollen tube elongation in tobacco modulate reactive oxygen species and nitric oxide homeostasis.

Several signaling pathways have been shown to be involved in the regulation of pollen germination and pollen tube elongation. Among others, exogenously applied polyamines were found to strongly affect pollen maturation, pollen tube emergence and elongation. In this study, our aim was to investigate the regulatory relation among exogenous polyamines, and endogenous reactive oxygen species and nitric oxide under pollen germination and the apical growth of pollen tube in tobacco plants. We have found that the various polyamines differentially affected the metabolism of nitric oxide and reactive oxygen species during the processes of pollen germination in the grain and the lengthening pollen tube. It is hypothesized that their differential effects might be related to their distinct influence on the endogenous nitric oxide and reactive oxygen species levels.