Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis

Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of Deferoxamine on spinal cord injury recovery. A rat model of Deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the Deferoxamine group were intraperitoneally injected with 100 mg/kg Deferoxamine 30 minutes before injury. Simultaneously, the Sham and Deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows:(1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group.(2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the Deferoxamine group than in the spinal cord injury group.(3) The iron concentration was lower in the Deferoxamine group than in the spinal cord injury group after injury.(4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the Deferoxamine group.(5) Real-time polymerase chain reaction revealed that, compared with the Deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2(ACSF2) and iron-responsive element-binding protein 2(IREB2) were up-regulated in the Deferoxamine group.(6) Deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that Deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury.     

Clinical clues for differential diagnosis between verruca plana and verruca plana‐like seborrheic keratosis

Sometimes the clinical differentiation between verruca plana (VP) and VP‐like seborrheic keratosis (SK) could be challenged. However, there have been no studies on this issue to date. The aim of this study was to elucidate clinical and dermoscopic differences between these two diseases, and also to suggest a diagnostic algorithm of VP and VP‐like SK without skin biopsy. The patients who had lesions clinically considered as VP or VP‐like SK were the target of our study. We took clinical and dermoscopic photos with informed consent and conducted a questionnaire. All patients had their diagnoses confirmed by biopsy. Thirty‐three patients were enrolled in our study. Seventeen patients were finally diagnosed with VP (51.5%) and 16 patients with VP‐like SK (48.5%). In clinical findings, VP‐like SK showed significantly more scattered distribution than VP (P = 0.039), which exhibited more clustered or grouped distribution (P = 0.039). In dermoscopic findings, brain‐like appearance was more commonly observed in VP‐like SK (P = 0.003) whereas VP showed more red dots or globular vessels (P = 0.017) and even‐colored light brown to yellow patch (P < 0.001). Sex, onset age, the size of each lesion, location, color and shape showed no significant differences between them (P > 0.05). Based on our results, we suggest a diagnostic algorithm using Koebner's phenomenon, dermoscopic findings, distribution of each lesion and biopsy for multiple VP‐like lesions in adults, and we think it will be a very useful diagnostic tool in daily clinical dermatological practice.     

Family Caregivers' Subjective Caregiving Burden,Quality of Life,and Depressive Symptoms Are Associated With Terminally Ill Cancer Patients' Distinct Patterns of Conjoint Symptom Distress and Functional Impairment in Their Last Six Months of Life

Context

Family caregivers constitute a critical component of the end-of-life care system with considerable cost to themselves. However, the joint association of terminally ill cancer patients' symptom distress and functional impairment with caregivers' subjective caregiving burden, quality of life (QOL), and depressive symptoms remains unknown.

Allergic fetal priming leads to developmental,behavioral and neurobiological changes in mice

The state of the mother''s immune system during pregnancy has an important role in fetal development and disruptions in the balance of this system are associated with a range of neurologic, neuropsychiatric and neurodevelopmental disorders. Epidemiological and clinical reports reveal various clues that suggest a possible association between developmental neuropsychiatric disorders and family history of immune system dysfunction. Over the past three decades, analogous increases have been reported in both the incidence of neurodevelopmental disorders and immune-related disorders, particularly allergy and asthma, raising the question of whether allergic asthma and characteristics of various neurodevelopmental disorders share common causal links. We used a mouse model of maternal allergic asthma to test this novel hypothesis that early fetal priming with an allergenic exposure during gestation produces behavioral deficits in offspring. Mothers were primed with an exposure to ovalbumin (OVA) before pregnancy, then exposed to either aerosolized OVA or vehicle during gestation. Both male and female mice born to mothers exposed to aerosolized OVA during gestation exhibited altered developmental trajectories in weight and length, decreased sociability and increased marble-burying behavior. Moreover, offspring of OVA-exposed mothers were observed to have increased serotonin transporter protein levels in the cortex. These data demonstrate that behavioral and neurobiological effects can be elicited following early fetal priming with maternal allergic asthma and provide support that maternal allergic asthma may, in some cases, be a contributing factor to neurodevelopmental disorders.