Anti-Inflammatory Effect of Columbianadin against D-Galactose-Induced Liver Injury In Vivo via the JAK2/STAT3 and JAK2/p38/NF-κB Pathways.

Angelicae pubescentis radix (APR) has been traditionally used for thousands of years in China to treat rheumatoid arthritis (RA), an autoimmune disorder. As the main active coumarin of APR, columbianadin (CBN) exhibits a significant anti-inflammatory effect in vitro. However, the anti-inflammatory activity and underlying mechanism of CBN in vivo remain unclear. This work aimed to elucidate the anti-inflammatory activity of CBN in vivo and its related signaling pathways in a D-Gal-induced liver injury mouse model. Analysis of biochemical indices (ALT and AST) and pro-inflammatory cytokines (IL-1ß and IL-6) in serum indicated that CBN significantly ameliorated D-Gal-induced liver injury. CBN treatment also significantly increased the activities of antioxidant enzymes (SOD, CAT, GPx), and decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) in liver tissue. Liver histology revealed that CBN treatment reduced hepatic inflammation. Western blot analysis indicated that CBN down-regulates the expression of phosphorylated JAK2, STAT3, MAPK, and NF-κB in the related signaling pathways. These findings support the traditional use of APR as a remedy for the immune system, and indicate that the JAK2/STAT3 and JAK2/p38/NF-κB signaling pathways may be important mechanisms for the anti-inflammatory activity of CBN in vivo.

Abnormal network properties and fiber connections of DMN across major mental disorders: a probability tracing and graph theory study.

The default mode network (DMN) is related to brain functions and its abnormalities were associated with mental disorders' pathophysiology. To further understand the common and distinct DMN alterations across disorders, we capitalized on the probability tracing method and graph theory to analyze the role of DMN across three major mental disorders. A total of 399 participants (156 schizophrenia [SCZ], 90 bipolar disorder [BP], 58 major depression disorder [MDD], and 95 healthy controls [HC]) completed magnetic resonance imaging (MRI)-scanning, clinical, and cognitive assessment. The MRI preprocessing of diffusion-tensor-imaging was conducted in FMRIB Software Library and probabilistic fiber tracking was applied by PANDA. This study had three main findings. First, patient groups showed significantly lower cluster coefficient in whole-brain compared with HC. SCZ showed significantly longer characteristic path compared with HC. Second, patient groups showed inter-group specificity in abnormalities of DMN connections. Third, SCZ was sensitive to left_medial_superior_frontal_gyrus (L_SFGmed)-right_anterior_cingulate_gyrus (R_ACG) connection relating to positive symptoms; left_ACG-right_ACG connection was the mania's antagonistic factor in BP. This trans-diagnostic study found disorder-specific structural abnormalities in the fiber connection of R_SFGmed-L_SFGmed-R_ACG_L_ACG within DMN, where SCZ showed more disconnections compared with other disorders. And these connections are diagnosis-specifically correlated to phenotypes. The current study may provide further evidence of shared and distinct endo-phenotypes across psychopathology.

The integrity of the white matter in first-episode schizophrenia patients with auditory verbal hallucinations: An atlas-based DTI analysis.

Auditory verbal hallucination (AVH) is one of the most remarkable symptoms of schizophrenia, with great impact on patients' lives and unclear pathogenesis. Neuroimaging studies have indicated that the development of AVHs is associated with white matter alteration, however, there are still inconsistencies in specific findings across previous investigations. The present study aimed to investigate the characteristics of the microstructural integrity of white matter (WM) in first-episode schizophrenia patients who experience auditory hallucinations. Atlas-based Diffusion Tensor Imaging (DTI) analysis was performed to evaluate the white matter integrity in 37 first-episode schizophrenia patients with AVH, 60 schizophrenia patients without AVH, and 50 healthy controls. Compared with the healthy controls group, AVH showed decreased mean fractional anisotropy (FA) in the genu and body of corpus callosum, right posterior corona radiata, left superior corona radiata, left external capsule, right superior fronto-occipital fasciculus, and higher mean diffusivity (MD) in genu of corpus callosum and left fornix and stria terminalis; whereas the nAVH group showed a much more significant reduction of FA and increased MD in broader brain regions. In addition, a significant positive correlation between FA and the severity of AVHs was observed in right posterior corona radiate. These observations collectively demonstrated that a certain degree of preserved fronto-temporal and interhemispheric connectivity in the early stage of schizophrenia might be associated with the brain capability to generate AVHs.