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.     

Suppression of PRDX4 inhibits cell proliferation and invasion of ectopic endometrial stromal cells in endometriosis

Abstract

Oxidative stress (OS) has been proposed to play a role in the development of EMs. Peroxiredoxins are a family of antioxidant proteins that exhibit peroxidase activity in a thioredoxin-dependent manner, protecting cells against OS. The Western blotting results showed that the relative expression of PRDX4 was significantly increased in ectopic endometria compared with the normal endometria of EMs-free (p?<?.05). The H₂O₂ concentration was also significantly higher in the ectopic endometrium. PRDX4 siRNA was transfected into primary ectopic endometrial stromal cells (EESCs). The viability of the transfected EESCs was measured by CCK-8 assay, and the results showed significantly decreased cell viability. Furthermore, the apoptosis rate and ROS generation in flow cytometry assays were significantly increased after the knockdown of PRDX4 expression (p?<?.05). Scratch assays and transwell assays revealed that decreased expression of PRDX4 mediated by siRNA inhibited EESC migration and invasion. In conclusion, these findings indicate the potential role of PRDX4 in the development of EMs and PRDX4 as a possible therapeutic target for EMs treatment.     

Is Atrial Fibrillation a Risk Factor for Gastroesophageal Reflux Disease Occurrence?

Recent studies have reported an association between gastroesophageal reflux disease (GERD) and atrial fibrillation (AF). The objective of the present study was to evaluate whether AF is one of the risk factors for GERD occurrence.In this hospital-based, retrospective, case–control study, the patients were classified into 2 groups. The patients diagnosed with new AF were assigned to the AF group (n = 1612); those diagnosed without AF and GERD were assigned to the control group (n = 1612). The subjects in the control group were selected from outpatients of total healthcare center without a history of AF or GERD, and matched for age and gender. We evaluated the incidence of GERD and risk factors for GERD occurrence between the 2 groups.The number of patients experiencing occurrence of GERD during the follow-up period was significantly higher in the AF group than those in the control group, respectively (129 patients vs 98 subjects, P = 0.037). The incidence of GERD was significantly higher in the AF group than in the control group by Kaplan–Meier analysis with log-rank test (P = 0.008). The AF group''s adjusted hazard ratio of GERD occurrence against that of the control group was 1.37 (95% confidence interval [CI]: 1.16–1.57; P = 0.009) according to Cox''s proportional hazard model.The presence of AF appears to increase the incidence of GERD and may be considered a risk factor for the development of GERD. Further, large prospective and cohort studies will be required to better establish the correlation of GERD with AF.     

Traumatic axonal injury of the cingulum in patients with mild traumatic brain injury: a diffusion tensor tractography study

The cingulum, connecting the orbitofrontal cortex to the medial temporal lobe, involves in diverse cognition functions including attention, memory, and motivation. To investigate the relationship between the cingulum injury and cognitive impairment in patients with chronic mild traumatic brain injury, we evaluated the integrity between the anterior cingulum and the basal forebrain using diffusion tensor tractography in 73 patients with chronic mild traumatic brain injury(39 males, 34 females, age 43.29 ± 11.42 years) and40 healthy controls(22 males, 18 females, age 40.11 ± 16.81 years). The patients were divided into three subgroups based on the integrity between the anterior cingulum and the basal forebrain on diffusion tensor tractography: subgroup A(n = 19 patients)-both sides of the anterior cingulum were intact; subgroup B(n= 36 patients)-either side of the anterior cingulum was intact; and subgroup C(18 patients)-both sides of the anterior cingulum were discontinued. There were significant differences in total Memory Assessment Scale score between subgroups A and B and between subgroups A and C. There were no significant differences in diffusion tensor tractography parameters(fractional anisotropy, apparent diffusion coefficient, and fiber volume) between patients and controls. These findings suggest that the integrity between the anterior cingulum and the basal forebrain, but not diffusion tensor tractography parameter, can be used to predict the cognitive function of patients with chronic mild traumatic brain injury. This study was approved by Yeungnam University Hospital Institutional Review Board(approval No. YUMC-2014-01-425-010) on August 16, 2017.     

Ethnic variation in deep lateral orbital anatomy and its implications on decompression surgery

Aim: To describe differences in the deep lateral orbital wall (specifically, trigone) between Chinese, Malay, Indian and Caucasian subjects

Methods: Single-centre retrospective Computed Tomogram (CT)-based study; 20 subjects of each ethnicity were used from existing databases, matched for gender, average age and laterality. Subjects below 16 years of age were excluded. DICOM image viewing software CARESTREAM Vue PACS (Carestream Health Inc., USA) and OsiriX version 7.5 (Pixmeo., Switzerland) were used to measure deep lateral wall length, thickness and volume, as well as orbital depth and statistical analyses performed using Statistical Package for Social Sciences version 21 (IBM, USA).

Results: In each group, there were 12 males (60%) and average age was not significantly different (p = 0.682–0.987). Using Chinese subjects as a reference, in Chinese, Malay, Indian and Caucasian subjects, mean trigone thickness was 13.68, 14.02, 11.60 (p < 0.001) and 13.80 mm, curved total wall length 45.23, 42.29 (p = 0.048), 41.91 (p = 0.020) and 45.00 mm, curved trigone length 23.03, 22.61, 17.19 (p = 0.011) and 18.76 mm (p = 0.030) and trigone volume 3120.97, 3221.01, 1613.66 (p < 0.001), 2498.46 mm³ (p = 0.059) respectively. Similarly, perpendicular orbital depth was 27.54, 24.97, 22.12 (p = 0.001) and 25.93 mm and diagonal orbital depth was 34.19, 33.27, 29.48 (p = 0.01) and 34.63 mm respectively.

Conclusions: Indian and, to a lesser extent, Caucasian subjects have smaller trigones compared to their Chinese and Malay counterparts. Indian subjects also have shallower orbits and due care should be taken during decompression surgery.