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Podocyte injury plays a key role in the production of proteinuria and is closely related to the progression of chronic kidney disease (CKD). Alleviating podocyte injury is beneficial to prevent the occurrence and development of CKD. tRNA-derived RNA fragments (tRFs) are associated with podocytes injury processes such as protein binding, cell adhesion, synapses, the actin cytoskeleton. Our previous data showed that tRF-003634 tightly correlated with podocyte injury, while its effect remains unclear. This study aimed to investigate the role of tRF-003634 in podocyte injury and the potential mechanisms. The expression level of tRF-003634, nephrin, podocin and tRF-003634 targeted toll-like receptor 4 (TLR4) in podocytes and kidney tissues were examined by quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry. The biochemical indices were monitored and renal pathological changes were assessed by hematoxylin and eosin PAS staining. Furthermore, potential target genes of tRF-003634 were screened using high-throughput mRNA sequencing, and then confirmed by RNA pulse-chase analysis. The results showed that tRF-003634 was downregulated in adriamycin (Adr)-induced podocyte injury. Overexpression of tRF-003634 increased the expression of nephrin and podocin in vivo and in vitro and alleviated podocyte injury. Meanwhile, overexpression of tRF-003634 alleviated proteinuria and renal pathological damage. In addition, high-throughput sequencing after overexpression of tRF-003634 showed that TLR4 might be a downstream target gene. tRF-003634 can alleviate podocyte injury by reducing the stability of TLR4 mRNA, possibly by competing with TLR4 mRNA to bind to YTH domain-containing protein 1 (YTHDC1). In conclusion, tRF-003634 was underexpressed in Adr-induced podocyte injury, and its overexpression alleviated podocyte injury in vitro and in vivo by reducing the stability of TLR4 mRNA. [ABSTRACT FROM AUTHOR]

Background: Psychogenic non epileptic seizures (PNES) are a frequent, disabling and costly disorder for which there is no consensual caring. They are considered as a dissociative disorder and they share many common characteristics with post-traumatic stress disorder (PTSD). Nevertheless, their pathophysiology is still unclear. In this study, we plan to obtain new data comparing functional brain activity of participants suffering from PNES, from PTSD and healthy controls via functional brain MRI during resting state and under emotional visual stimulation. The protocol presented hereunder describes an observational study with no direct treatment implication. Nevertheless, it could lead to a better understanding of PNES and to identifying targets for specialised cares of post-traumatic or dissociative disorders, like repetitive transcranial magnetic stimulation. Methods & analysis: This is a prospective, single-centre, interventional, non-randomized, open, controlled and exploratory clinical study. It will involve 75 adult French, right-handed women in 3 groups, either suffering from PNES or PTSD, or healthy controls. An informed consent will be signed by each participant. All of them will be given psychiatric tests to assess dissociation and alexithymia, psychopathological profile and history, and emotional recognition. Each participant will undergo a functional brain MRI. We will record anatomical images and five functional imaging sequences including emotional periodic oscillatory stimulation, standard emotional stimulation, Go / No Go task under emotional stimulation, and resting state. Analysis will include a descriptive analysis of all participants and the treatment for functional magnetic resonance imaging images of each sequence. Registration, ethics & dissemination: This study was approved the regional Protection of Persons Committee under the reference 16.10.01 and by the French National Medical Security Agency under the reference 2016-A01295-46. The protocol and results will be published in peer-reviewed academic medical journals and disseminated to research teams, databases, specialised media and concerned patients' organisations. [ABSTRACT FROM AUTHOR]