TAK1 inhibition mitigates intracerebral hemorrhage-induced brain injury through reduction of oxidative stress and neuronal pyroptosis via the NRF2 signaling pathway

IntroductionIntracerebral hemorrhage (ICH) often triggers oxidative stress through reactive oxygen species (ROS). Transforming growth factor-β-activated kinase 1 (TAK1) plays a pivotal role in regulating oxidative stress and inflammation across various diseases. 5Z-7-Oxozeaenol (OZ), a specific inhibitor of TAK1, has exhibited therapeutic effects in various conditions. However, the impact of OZ following ICH and its underlying molecular mechanisms remain elusive. This study aimed to explore the possible role of OZ in ICH and its underlying mechanisms by inhibiting oxidative stress-mediated pyroptosis. MethodsAdult male Sprague-Dawley rats were subjected to an ICH model, followed by treatment with OZ. Neurobehavioral function, blood-brain barrier integrity, neuronal pyroptosis, and oxidative stress markers were assessed using various techniques including behavioral tests, immunofluorescence staining, western blotting, transmission electron microscopy, and biochemical assays.ResultsOur study revealed that OZ administration significantly inhibited phosphorylated TAK1 expression post-ICH. Furthermore, TAK1 blockade by OZ attenuated blood-brain barrier (BBB) disruption, neuroinflammation, and oxidative damage while enhancing neurobehavioral function. Mechanistically, OZ administration markedly reduced ROS production and oxidative stress by facilitating nuclear factor-erythroid 2-related factor 2 (NRF2) nuclear translocation. This was accompanied by a subsequent suppression of the NOD-like receptor protein 3 (NLRP3) activation-mediated inflammatory cascade and neuronal pyroptosis. DiscussionOur findings highlight that OZ alleviates brain injury and oxidative stress-mediated pyroptosis via the NRF2 pathway. Inhibition of TAK1 emerges as a promising approach for managing ICH

Secretome of Olfactory Mucosa Mesenchymal Stem Cell, a Multiple Potential Stem Cell

Nasal olfactory mucosa mesenchymal stem cells (OM-MSCs) have the ability to promote regeneration in the nervous system in vivo. Moreover, with view to the potential for clinical application, OM-MSCs have the advantage of being easily accessible from patients and transplantable in an autologous manner, thus eliminating immune rejection and contentious ethical issues. So far, most studies have been focused on the role of OM-MSCs in central nervous system replacement. However, the secreted proteomics of OM-MSCs have not been reported yet. Here, proteins secreted by OM-MSCs cultured in serum-free conditions were separated on SDS-PAGE and identified by LC-MS/MS. As a result, a total of 274 secreted proteins were identified. These molecules are known to be important in neurotrophy, angiogenesis, cell growth, differentiation, and apoptosis, and inflammation which were highly correlated with the repair of central nervous system. The proteomic profiling of the OM-MSCs secretome might provide new insights into their nature in the neural recovery. However, proteomic analysis for clinical biomarkers of OM-MSCs needs to be further studied

The analysis and research on variable operating condition of exhaust steam and waste heat Cascade utilization system of air cooling heating unit

The series and parallel exhaust heat cascade utilization system was adopted by the large direct air cooling heating units. On the one hand, this system could reduce the adverse impact on power generation; on the other hand, it could reduce the temperature difference of heat transfer through step by step heating, the irreversible loss could be reduced, and the energy utilization efficiency could be made higher. On the basis of grasping the design performance of exhaust steam utilization system and the variable operating performance of main equipment by analysing the data of typical operating conditions, the optimization analysis model of heat pump group and the whole plant was established by this paper. The performance of heat pump unit under variable operating conditions was analysed and calculated, the influence of different exhaust pressure and backwater temperature on the economy of the whole machine was analysed, and the optimal operation mode of the heat pump was obtained. Finally, the pumping and condensing ratio curves under different conditions of winter heating conditions were determined, which could guide the optimal operation of heat pump units. It also provided technical support and basis for deep peak regulation or flexible transformation of heating units

The analysis and research on variable operating condition of exhaust steam and waste heat Cascade utilization system of air cooling heating unit

The series and parallel exhaust heat cascade utilization system was adopted by the large direct air cooling heating units. On the one hand, this system could reduce the adverse impact on power generation; on the other hand, it could reduce the temperature difference of heat transfer through step by step heating, the irreversible loss could be reduced, and the energy utilization efficiency could be made higher. On the basis of grasping the design performance of exhaust steam utilization system and the variable operating performance of main equipment by analysing the data of typical operating conditions, the optimization analysis model of heat pump group and the whole plant was established by this paper. The performance of heat pump unit under variable operating conditions was analysed and calculated, the influence of different exhaust pressure and backwater temperature on the economy of the whole machine was analysed, and the optimal operation mode of the heat pump was obtained. Finally, the pumping and condensing ratio curves under different conditions of winter heating conditions were determined, which could guide the optimal operation of heat pump units. It also provided technical support and basis for deep peak regulation or flexible transformation of heating units.</jats:p