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In morphometric neuroimaging studies, the relationship between brain structural changes and the antidepressant treatment response in patients with major depressive disorder has been explored to search depression-trait biomarkers. Although patients were treated with serotonin-related drugs, whether the same treatment resulted in remission and non-remission in depressed patients is currently under investigation. We recruited 25 depressed patients and 25 healthy controls and acquired volumetric magnetic resonance imaging of each participant. We used the shape index and curvedness to classify cortical shapes and quantify shape complexities, respectively, in studying the pharmacological effect on brain morphology. The results showed that different regions of structural abnormalities emerged between remitting and non-remitting patients when contrasted with healthy controls. In addition to comparing structural metrics in each cortical parcellation, similar to the traditional voxel-based morphometric method, we highlighted the importance of structural integrity along the serotonin pathway in response to medication treatment. We discovered that disrupted serotonin-related cortical regions might cause non-remission to antidepressant treatment from a pharmacological perspective. The anomalous areas manifested in non-remitting patients were mainly in the frontolimbic areas, which can be used to differentiate remitting from non-remitting participants before medication treatment. Because non-remission is the failure to respond to treatment with serotonin-related drugs, our method may help clinicians choose appropriate medications for non-remitting patients. [ABSTRACT FROM AUTHOR]

Background: It is of importance to minimize ischemia reperfusion (I/R) injury during liver operations. Reducing the inflammatory reaction is an effective way to achieve this goal. Notably, adiponectin (APN) was found to have anti-inflammatory activity in heart and renal I/R injury. Herein, we investigated the role of APN in liver I/R injury. Methods: Wistar rats were randomized to four groups: (1) sham group; (2) I/R control group; (3) I/R+APN group; and (4) I/R+APN+AMPK inhibitor group. Liver and blood samples were collected 6h and 24h after reperfusion. Liver function and histopathologic changes were assessed. Macrophage and neutrophil infiltration was detected by immunohistochemistry staining, while pro-inflammatory cytokines and chemokines released in the liver were measured using ELISA and RT-PCR, respectively. Apoptosis was analyzed by TUNEL staining and caspase-3 expression in the liver. Downstream molecules of APN were investigated by Western blotting. Results: Circulatory APN was down-regulated during liver I/R. When exogenous APN treatment was administered during liver I/R, alanine transaminase (ALT) and aspartate aminotransferase (AST) were decreased, and less hepatocyte necrosis was observed. Less inflammatory cell infiltration and pro-inflammatory cytokines/chemokines release were also observed in the I/R+APN group when compared with the I/R control group. APN treatment also reduced hepatocyte apoptosis, evidenced by reduced TUNEL positive cells and less caspase-3 expression in the reperfused liver. Finally, the AMPK/eNOS pathway was found to be activated by APN, and administration of an AMPK inhibitor reversed the beneficial effects of APN. Conclusion: APN can protect the liver from I/R injury by reducing the inflammatory response and hepatocyte apoptosis, a process that likely involves the AMPK/eNOS pathway. The current study provides a potential pharmacologic target for liver I/R injury. [ABSTRACT FROM AUTHOR]

Msb1 is not essential for growth in the budding yeast Saccharomyces cerevisiae since msb1Δ cells do not display obvious phenotypes. Genetic studies suggest that Msb1 positively regulates Cdc42 function during bud development, since high-copy MSB1 suppressed the growth defect of temperature-sensitive cdc24 and cdc42 mutants at restrictive temperature, while deletion of MSB1 showed synthetic lethality with cdc24, bem1, and bem2 mutations. However, the mechanism of how Msb1 regulates Cdc42 function remains poorly understood. Here, we show that Msb1 localizes to sites of polarized growth during bud development and interacts with Cdc42 in the cells. In addition, Msb1 interacts with Boi1 and Boi2, two scaffold proteins that also interact with Cdc42 and Bem1. These findings suggest that Msb1 may positively regulate Cdc42 function by interacting with Cdc42, Boi1, and Boi2, which may promote the efficient assembly of Cdc42, Cdc24, and other proteins into a functional complex. We also show that Msb1 interacts with Rho1 in the cells and Msb1 overproduction inhibits the growth of rho1-104 and rho1-3 but not rho1-2 cells. The growth inhibition appears to result from the down-regulation of Rho1 function in glucan synthesis, specifically during early stage of bud development. These results suggest that Msb1 may coordinate Cdc42 and Rho1 functions during early stage of bud development by promoting Cdc42 function and inhibiting Rho1 function. Msb1 overproduction also affects cell morphology, septin organization, and causes increased, aberrant deposition of 1,3-β-glucan and chitin at the mother-bud neck. However, the stimulation of glucan synthesis mainly occurs during late, but not early, stage of bud development. [ABSTRACT FROM AUTHOR]

Transarterial chemoembolization (TACE) has therapeutic effects in patients with unresectable hepatocellular carcinoma (HCC), but its impact on the cellular immune response during disease progression is largely unknown. Here we conducted a prospective study to evaluate the effect of TACE on immune status and to identify prognostic immune markers governing treatment success. In this study, 51 stage III HCC patients, 28 stage I HCC patients (TNM classification) and 20 healthy donors were enrolled. Flow cytometry and cytometric bead array were used to evaluate the circulating immune cell subsets, including CD4+ T cells (Th1, Th17 and Treg cells), CD8+ T cells, NK cells, and NKT cells, and plasma cytokines before TACE and 30 days after TACE. Interestingly, among those immune parameters, the frequency of circulating Th17 cells was higher in stage III HCC patients than in stage I HCC patients (P = 0.015) and healthy donors (P<0.001). Moreover, an increased frequency of circulating Th17 cells was observed 30 days after TACE (Th17D30) compared with the baseline level (P = 0.036). Kaplan-Meier analysis demonstrated that Th17D30 was positively associated with overall survival (OS; P = 0.007) and time to progression (TTP; P = 0.009). Multivariate Cox analysis revealed that Th17D30 was an independent prognostic factor for OS (HR = 0.317, P = 0.032) and TTP (HR = 0.304, P = 0.010). These results provide a potential prognostic marker for stage III HCC patients undergoing TACE and may be useful for identifying patients who can benefit from adjuvant immunotherapies. [ABSTRACT FROM AUTHOR]

Background: Simple sequence repeats (SSRs) are ubiquitous in eukaryotic genomes. Chrysanthemum is one of the largest genera in the Asteraceae family. Only few Chrysanthemum expressed sequence tag (EST) sequences have been acquired to date, so the number of available EST-SSR markers is very low. Methodology/Principal Findings: Illumina paired-end sequencing technology produced over 53 million sequencing reads from C. nankingense mRNA. The subsequent de novo assembly yielded 70,895 unigenes, of which 45,789 (64.59%) unigenes showed similarity to the sequences in NCBI database. Out of 45,789 sequences, 107 have hits to the Chrysanthemum Nr protein database; 679 and 277 sequences have hits to the database of Helianthus and Lactuca species, respectively. MISA software identified a large number of putative EST-SSRs, allowing 1,788 primer pairs to be designed from the de novo transcriptome sequence and a further 363 from archival EST sequence. Among 100 primer pairs randomly chosen, 81 markers have amplicons and 20 are polymorphic for genotypes analysis in Chrysanthemum. The results showed that most (but not all) of the assays were transferable across species and that they exposed a significant amount of allelic diversity. Conclusions/Significance: SSR markers acquired by transcriptome sequencing are potentially useful for marker-assisted breeding and genetic analysis in the genus Chrysanthemum and its related genera. [ABSTRACT FROM AUTHOR]