Background: The Rab13-JRAB system transports cell adhesion molecules. Results: JRAB interacts with actinins and F-actin and spatiotemporally regulates actin dynamics via a conformational change that is dependent upon Rab13. Conclusion: Rab13 and JRAB regulate reorganization of the actin cytoskeleton throughout epithelial junctional development from establishment to maturation of cell-cell adhesion. Significance: The Rab13-JRAB system may simultaneously coordinate vesicle transport and actin cytoskeletal organization.

We previously showed that Rab13 and its effector protein, junctional Rab13-binding protein (JRAB)/molecules interacting with CasL-like 2 (MICAL-L2), regulate junctional development by modulating cell adhesion molecule transport and actin cytoskeletal reorganization in epithelial cells. Here, we investigated how JRAB regulates reorganization of the actin cytoskeleton in NIH3T3 fibroblasts, in an attempt to obtain novel insights into the mechanism of JRAB action. To this end, we expressed mutant proteins that adopt a constitutively open or closed state and then examined effect on cellular morphology of the resulting actin cytoskeletal reorganization. Expression of the JRABDCT mutant (constitutively 'closed' state) induced stress fibers, whereas expression of the JRABDCC mutant (constitutively 'open' state) caused cell spreading with membrane ruffles. Next, we identified the proteins involved in JRAB-induced rearrangement of actin cytoskeleton leading to morphological changes. In NIH3T3 cells expressing HA-JRABDCC, filamin, an actin cross-linking protein, coimmunoprecipitated with HA-JRABDCC. Expression of ASB2 induced degradation of all three filamin isoforms and inhibited the JRABDCC-induced cell spreading. Consistent with our previous results, actinin-1/-4 were also immunoprecipitated with HA-JRABDCC. However, actinin-1/-4 have no effect on the cell spreading regulated by JRABDCC. These data suggest that JRAB contributes to the rearrangement of the actin cytoskeleton during cell spreading via filamins.

Objectives Acute kidney injury (AKI) is a critical clinical event characterized by a reduction in the excretory function of the kidneys. N-acetylcysteine (NAC), N-acetylmethionine (NAM) and N-acetylglucosamine (NAG) are antioxidants with scanty known genetic mechanisms. We aimed to assess both kidney injury molecule-1 (KIM-1) and growth-arrested DNA damage-inducible gene-153 (GADD-153) genes expression in paracetamol (PA) induced AKI. Also, to recognize whether NAC, NAM and/or NAG have roles in altering the expression of these genes for ameliorating the AKI induced by PA. Methods The present preliminary study achieved the AKI model by oral administration of PA therapeutic dose for 15 days in experimental male rats. Serum urea, creatinine, and renal oxidative stress parameters were analyzed. Genetic expression of KIM-1 and GADD-153 were determined using real time-PCR. Results Significant elevations of serum urea, creatinine and nitric oxide in renal tissue after PA administration; however, total thiol content was reduced. In addition, both KIM-1 and GADD-153 were upregulated. These biochemical alterations were improved after using NAC and partially after NAM; however, NAG had little effect. Conclusions Up-regulation of both KIM-1 and GADD-153 occur in AKI induced by PA, which was significantly reversed by NAC.

Backgrounds The incidence of non-alcoholic fatty liver disease (NAFLD) has been significantly growing in recent years. Although the pathophysiology of fibrosis progression in NAFLD is not yet known, oxidative stress and inflammation have been known to have a major role in the development of NASH. Understanding the impact of micronutrients in NAFLD could potentially help us better understand NAFLD pathogenesis. Aims Assessing the serum levels of Zn, Se, and Vitamin E and their relation to the development of hepatic fibrosis in NAFLD patients. Methods This study included 80 NAFLD patients and 40 healthy controls. All of the patients were subjected to abdominal ultrasound and FibroScan examination (to estimate hepatic fibrosis and steatosis degree), and the serum levels of Zn, Se, and vitamin E were evaluated. Results A statistically significant difference in the serum levels of Zn and Se was observed between the NAFLD group and the control group (P-value = 0.04 and 0.05, respectively). The serum levels of Zn and Se were independently related to the presence of hepatic fibrosis in NAFLD. However, serum vitamin E was not related to the severity of NAFLD. Furthermore, no significant difference in the levels of Zn, Se, and vitamin E was observed between the different groups of NAFLD patients categorized according to the degree of steatosis and the control group. Conclusions Reduced serum levels of Zn and Se can be considered a possible risk factor for hepatic fibrosis in NAFLD. Deficiency in these micronutrients could play a role in the pathogenesis of NAFLD.

Background Epilepsy is one of the most common neurological disorders, and it places a significant economic strain on the healthcare system around the world. Although the exact mechanism of epilepsy has yet to be illustrated, various pathogenic cascades involving neurotransmitters and trace elements have been reported. We aimed to investigate the serum levels of growth-associated protein-43 (GAP-43) and neurotrophin-3 (NT-3) among cohort of Egyptian children with epilepsy and correlate these biomarkers with their zinc levels. Methods This case–control study included 50 pediatric patients with epilepsy who were comparable with 50 controls. Neurological assessment and electroencephalogram (EEG) were done to all included children. Biochemical measurements of serum GAP-43 and NT-3 using enzyme linked immunosorbent assays (ELISA), and total antioxidant capacity (TAC) and zinc using colorimetric assays, were performed to all participants. Results There was significantly frequent positive parental consanguinity among cases with significantly frequent generalized onset seizures (94%) than simple partial seizure (6%). There were significantly lower serum GAP-43 and zinc levels with significantly higher TAC among cases vs. the controls, p˂0.05 for all. There was no significant difference in the serum levels of NT-3 among epileptic children vs. the controls, p = 0.269. Serum Zn was positively correlated with GAP-43 level among epileptic children (r = 0.381, p = 0.006). Serum GAP-43 in diagnosing childhood epilepsy at cut-off point ≤ 0.6 ng/mL showed 78% sensitivity, 62% specificity, positive predictive value (PPV) = 50.6%, negative predictive value (NPP) = 84.9% with AUC = 0.574. Conclusion GAP-43 can be considered a sensitive good negative biomarker in childhood epilepsy which correlated positively with the zinc status.