Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52

A major impedance to neuronal regeneration after peripheral nerve injury (PNI) is the activation of various programmed cell death mechanisms in the dorsal root ganglion. Ferroptosis is a form of programmed cell death distinguished by imbalance in iron and thiol metabolism, leading to lethal lipid peroxidation. However, the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear. Ferroportin (Fpn), the only known mammalian nonheme iron export protein, plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis. Here, we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis. We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn, and stimulation of lipid peroxidation. Early administration of the potent arterial vasodilator, hydralazine (HYD), decreases the ubiquitination of Fpn after PNI by binding to UBA52, leading to suppression of neuronal cell death and significant acceleration of axon regeneration and motor function recovery. HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Therapeutic effect in patients with coronary heart disease based on information analysis from Traditional Chinese Medicine four diagnostic methods

OBJECTIVE:To study information gained by Traditional Chinese Medicine(TCM)four diagnostic methods and characteristics of syndrome development before and after treatment in patients with coronary heart disease,and to probe into assessment indexes of therapeutic effects with distinctive TCM features.METHODS:Information from the four diagnostic methods before and after treatment in 100 patients with coronary heart disease was collected using the TCM interrogation scale,a pulse condition instrument,a tongue-face diagnosis instrument,anda voice diagnosis information collection system.Changes in the four diagnostic method results from before and after treatment were analyzed with frequency analysis and t-test methods.RESULTS:Before treatment,deficiency syndrome complicated with hyperactivity of pathogenic factors was most common.After treatment,deficiency syndrome was most common.This change from complex syndromes to single syndromes indicates disease and syndrome alleviation.Frequencies of symptoms gained by interrogation after treatment for syndrome of deficiency of heart-Qi,syndrome of deficiency of heart-Yin,and turbid phlegm syndrome were all less severe than those before treatment.Parameters of face color,color on all sub-regions of tongue,color of tongue fur,septic and greasy fur,and lip color after treatment all had significant changes.After treatment,part of the voice diagnosis parameters in the deficiency of heart-Yin and turbid phlegm syndromes had significant changes,but no significant changes were found in the deficiency of heart-Qi syndrome.CONCLUSION:Use of the TCM four diagnostic methods can provide an effective basis forTCM syndrome diagnosis,observation of development of state of illness,and evaluation of clinical therapeutic effects.