LncRNA NORAD engages in psoriasis by binding to miR-26a to regulate keratinocyte proliferation.

BACKGROUND: Psoriasis is a chronic, inflammatory skin disease. It was reported that lncRNA Non-coding RNA-activated by DNA damage (NORAD) has potential regulatory effects on skin diseases. Our previous studies found that lncRNA NORAD was highly expressed and its potential target miR-26a was down-regulated in psoriasis model mice. Here, we aimed to investigate the role of NORAD in the development of psoriasis. METHODS: IL-22/LPS (interleukin-22/lipopolysaccharide)-stimulated HaCaT (human immortalized keratinocytes) cell model and imiquimod-induced mouse model were established. Keratin 6 (K6), Keratin 16 (K16), Keratin 17 (K17), and Cell division cycle 6 (CDC6) levels were detected by western blot. Cell activity was detected by CCK-8, MTT, and EdU assays. Quantitative real-time PCR was performed to examine the levels of NORAD, miR-26a, CDC6, K6, K16, and K17. Haematoxylin-eosin staining was applied to observe the degree of skin thickening and hyperplasia. Fluorescence in situ hybridization detects the location of NORAD. RNA immunoprecipitation, RNA pull-down, and Luciferase test were performed to detect the interaction between NORAD and miR-26a. RESULTS: In IL-22/LPS-stimulated HaCaT cells, NORAD, CDC6, and keratinocyte proliferation-related proteins (K6, K16, and K17) were up-regulated and miR-26a was down-regulated. Cell survival and proliferation were also increased. However, the results were reversed after interference with NORAD. Also, in vitro experiments revealed that NORAD negatively regulated miR-26a. In IL-22/LPS-stimulated HaCaT cells and skin of imiquimod-induced mice, we found that lower NORAD resulted in an increase of miR-26a and a decrease of CDC6, further decreased levels of keratinocyte proliferation-related proteins (K6, K16, and K17).

The effects of cognitive behavioral therapy on the whole brain structural connectome in unmedicated patients with obsessive-compulsive disorder.

Cognitive behavioral therapy (CBT) is considered a first-line treatment for patients with obsessive-compulsive disorder (OCD), and it possesses advantages over pharmacological treatments in stronger tolerance to distress, lower rates of drop out and relapse, and no physical "side-effects". Previous studies have reported CBT-related alterations in focal brain regions and connections. However, the effects of CBT on whole-brain structural networks have not yet been elucidated. Here, we collected diffusion MRI data from 34 unmedicated OCD patients before and after 12 weeks of CBT. Fifty healthy controls (HCs) were also scanned twice at matched intervals. We constructed individual brain white matter connectome and performed a graph-theoretical network analysis to investigate the effects of CBT on whole-brain structural topology. We observed significant group-by-time interactions on the global network clustering coefficient and the nodal clustering of the left lingual gyrus, the left middle temporal gyrus, the left precuneus, and the left fusiform gyrus of 26 CBT responders in OCD patients. Further analysis revealed that these CBT responders showed prominently higher global and nodal clustering compared to HCs at baseline and reduced to normal levels after CBT. Such significant changes in the nodal clustering of the left lingual gyrus were also found in 8 CBT non-responders. The pre-to-post decreases in nodal clustering of the left lingual gyrus and the left fusiform gyrus positively correlated with the improvements in obsessive-compulsive symptoms in the CBT-responding patients. These findings indicated that the network segregation of the whole-brain white matter network in OCD patients was abnormally higher and might recover to normal after CBT, which provides mechanistic insights into the CBT response in OCD and potential imaging biomarkers for clinical practice.

Abnormalities of white matter microstructure in unmedicated patients with obsessive-compulsive disorder: Changes after cognitive behavioral therapy.

BACKGROUND: Cognitive behavioral therapy (CBT) is an effective treatment for Obsessive-compulsive disorder (OCD). Structural and functional white matter defects may suggest a vital neurobiological basis of OCD. However, the effects of CBT on white matter in OCD remain unknown. OBJECTIVE: The aim was to investigate white matter changes and the effect of CBT on white matter in OCD patients. METHODS: Fractional anisotropy (FA) maps were acquired using DTI. Participants included 85 patients with OCD and 90 healthy controls. VBM was then performed to detect regions with significant group differences. RESULTS: Obsessive-compulsive disorder patients exhibited significantly reduced FA values in bilateral OFC, right cerebellum, and left SPG, while higher FA values were observed in right PUT compared with healthy controls. Following CBT, OCD patients showed higher FA values in right MFG, left OFC, right cerebellum, and left MTG, and decreased FA values in right PUT in comparison with pretreatment. Furthermore, FA values in the left OFC of patients were significantly positively correlated with the Y-BOCS and its associated Compulsions subscale, and FA values in the right PUT were positively correlated with Compulsions subscale. In addition, the percentage change in FA values in left MTG was positively correlated with the percentage reduction in Compulsions subscale, while the percentage change in FA values in left OFC and right PUT was negatively correlated with the percentage reductions in Obsessive and Compulsions subscale, respectively. CONCLUSIONS: Our findings demonstrate the abnormalities of white matter microstructure in unmedicated patients with OCD. These abnormalities may be partly reversed by CBT.