Search

Lhermitte-Duclos Disease is a rare clinical entity involving a dysplastic lesion of the cerebellum. The dysplastic cerebellar ganglioblastoma is often seen in association with Cowden Syndrome, an autosomal dominant disorder consisting of a mutation in the phosphatase and homologous tensin (PTEN) gene. Characteristic findings on neuroimaging allow for a pre-operative diagnosis to be made, which guides further management of the condition. This report describes the diagnosis and management of Lhermitte-Duclos Disease in a 51-year-old lady, spanning a period of almost seven years. The characteristic radiological and histological findings are presented, along with the clinical features associated with Cowden Syndrome. This patient ultimately underwent surgical intervention for symptomatic relief, which is described here. [ABSTRACT FROM AUTHOR]

Epilepsy is a common chronic neurological disorder with high prevalence that profoundly affects millions of people worldwide. Inflammatory dysregulation affects central nervous system disorders including epilepsy, and YTHDF1, the most common ''reader'' of m6A and m6A-binding protein, can attenuate the inflammatory response and activate PTEN, and here we aimed to investigate its effect on epilepsy through epigenetics. All mice were injected intraperitoneally with 12 mg/kg of sea manic acid to establish an epilepsy model, and the epileptic behaviors of the mice were classified into 6 grades; epileptic behaviors of grade 3 or above were defined as seizures, and consecutive epileptic seizures of more than 30 min were considered as successful modeling. Mouse behavior was examined using the Morris Water Maze tracking assay; inflammatory factors IL-6, TNF-α, and IL-1β were detected by qPCR/WB/ELISA; cell activity was analyzed by CCK-8; apoptotic markers were identified by immunofluorescence assay and Western blot analysis. YTHDF1 knockout mice have poor spatial memory capacity and sensitivity to external stimuli. Under the influence of YTHDF1, the neuroinflammation and nseuron death decreased. YTHDF1 works by repressing the production of pro-inflammatory cytokines and the activation of astrocytes. It was found that YTHDF1 epigenetically activates PTEN through m6A modification, activates glial cells and represses pro-inflammatory cytokines production and inhibits the development of epilepsy.

Objectives Cowden syndrome (CS) is a multisystem disease with an elevated lifetime risk of internal malignancy. We aim to assess the role of PTEN immunostain as a screening test for CS in a variety of common CS-associated neoplasms, with a particular focus on cutaneous tumors. Methods We retrospectively searched for patients meeting criteria for CS and/or demonstrating germline PTEN mutation from 2008 to 2022. We then performed PTEN immunostains on tumors of these patients as well as control cases. Results Our study included 30 patients with CS who had a total of 25 CS-associated malignancies (13 thyroid, 8 breast, and 4 endometrial carcinomas). Specifically, there were 11 patients with biopsy-confirmed CS-associated cutaneous neoplasms, including 1 patient with multiple trichilemmomas and 3 with multiple sclerotic fibromas. In total, 45 CS-associated tumors (6 trichilemmomas, 7 sclerotic fibromas, 5 thyroid carcinomas, 18 adenomatous thyroid nodules, 6 breast carcinomas, and 3 endometrial carcinomas) and 31 non-CS cases (9 trichilemmomas, 5 sclerotic fibromas, 8 adenomatous thyroid nodules, and 3 thyroid, 3 breast, and 3 endometrial carcinomas) were available for PTEN immunohistochemical staining. PTEN expression was lost in 43 (96%) of 45 CS-associated lesions and retained in 30 (97%) of 31 sporadic tumors. The overall sensitivity and specificity of PTEN loss of expression as a screening test for CS were 96% and 97%, respectively. Conclusions PTEN immunohistochemistry on CS-associated tumors, especially trichilemmomas, can serve as a readily accessible and cost-effective screening test for CS. [ABSTRACT FROM AUTHOR]

Epilepsy is a common chronic neurological disorder with high prevalence that profoundly affects millions of people worldwide. Inflammatory dysregulation affects central nervous system disorders including epilepsy, and YTHDF1, the most common "reader" of m6A and m6A-binding protein, can attenuate the inflammatory response and activate PTEN, and here we aimed to investigate its effect on epilepsy through epigenetics. All mice were injected intraperitoneally with 12 mg/kg of sea manic acid to establish an epilepsy model, and the epileptic behaviors of the mice were classified into 6 grades; epileptic behaviors of grade 3 or above were defined as seizures, and consecutive epileptic seizures of more than 30 min were considered as successful modeling. Mouse behavior was examined using the Morris Water Maze tracking assay; inflammatory factors IL-6, TNF-α, and IL-1β were detected by qPCR/WB/ELISA; cell activity was analyzed by CCK-8; apoptotic markers were identified by immunofluorescence assay and Western blot analysis. YTHDF1 knockout mice have poor spatial memory capacity and sensitivity to external stimuli. Under the influence of YTHDF1, the neuroinflammation and nseuron death decreased. YTHDF1 works by repressing the production of pro-inflammatory cytokines and the activation of astrocytes. It was found that YTHDF1 epigenetically activates PTEN through m6A modification, activates glial cells and represses pro-inflammatory cytokines production and inhibits the development of epilepsy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)