Cellular Stress and Molecular Responses in Bladder Ischemia

The concept of bladder ischemia as a contributing factor to detrusor overactivity and lower urinary tract symptoms (LUTS) is evolving. Bladder ischemia as a consequence of pelvic arterial atherosclerosis was first documented in experimental models and later in elderly patients with LUTS. It was shown that early-stage moderate ischemia produces detrusor overactivity, while prolonged severe ischemia provokes changes consistent with detrusor underactivity. Recent studies imply a central role of cellular energy sensors, cellular stress sensors, and stress response molecules in bladder responses to ischemia. The cellular energy sensor adenosine monophosphate-activated protein kinase was shown to play a role in detrusor overactivity and neurodegeneration in bladder ischemia. The cellular stress sensors apoptosis signal-regulating kinase 1 and caspase-3 along with heat shock proteins were characterized as important contributing factors to smooth muscle structural modifications and apoptotic responses in bladder ischemia. Downstream pathways seem to involve hypoxia-inducible factor, transforming growth factor beta, vascular endothelial growth factor, and nerve growth factor. Molecular responses to bladder ischemia were associated with differential protein expression, the accumulation of non-coded amino acids, and post-translational modifications of contractile proteins and stress response molecules. Further insight into cellular stress responses in bladder ischemia may provide novel diagnostic and therapeutic targets against LUTS.

Structural and molecular bases to IRE1 activity modulation

The Unfolded Protein response is an adaptive pathway triggered upon alteration of endoplasmic reticulum (ER) homeostasis. It is transduced by three major ER stress sensors, among which the Inositol Requiring Enzyme 1 (IRE1) is the most evolutionarily conserved. IRE1 is an ER-resident type I transmembrane protein exhibiting an ER luminal domain that senses the protein folding status and a catalytic kinase and RNase cytosolic domain. In recent years, IRE1 has emerged as a relevant therapeutic target in various diseases including degenerative, inflammatory and metabolic pathologies and cancer. As such several drugs altering IRE1 activity were developed that target either catalytic activity and showed some efficacy in preclinical pathological mouse models. In this review, we describe the different drugs identified to target IRE1 activity as well as their mode of action from a structural perspective, thereby identifying common and different modes of action. Based on this information we discuss on how new IRE1-targeting drugs could be developed that outperform the currently available molecules.

Measurements of Excavation Damaged Zone by Using Fiber Bragg Grating Stress Sensors

In this paper, a Fiber Bragg Grating (FBG) stress sensor is developed to measure the stress variation between the lower Excavation Damaged Zone (EDZ) and the upper undistributed rock. The disturbance brought by the environmental temperature can be differentially compensated with two FBGs mounted symmetrically on the spokes. Through finite element analysis, it can be known that the direct stress and shear stress are pointed at the angles of 45° and 60° on both sides of the coal mine roadway, respectively. The anchor ends of the sensors are installed into the upper undistributed rock and the bolt tails of the mine roadway with a depth of 700 m and fastened by nuts to secure the load sensing device on the surface of the rock. When the shallow foundation of surrounding rock is pressed and deformed toward the coal mining road, the structural modifications can be converted into the stress of rock bolt and the strain of spoke. Thus, the FBG mounted on the surface of the spoke receives the shift information of the Bragg wavelength. The monitoring results indicate that the FBG stress sensors are sensitive to the variation of the EDZ. During the blasting, the stress amplitude varies from 40.256 to 175.058 kPa, and the creep time changes from 21 to 74 min. The proposed method can be applied in the field of underground coal mines for safety condition monitoring of the EDZ and forecasting the coal mine roadway stability.

Reciprocal regulation of metabolic and stress sensors

Reciprocal regulation of metabolic and stress sensors