Reduced Levels of NR1 and NR2A with Depression-Like Behavior in Different Brain Regions in Prenatally Stressed Juvenile Offspring

Adolescence is a time of continued brain maturation, particularly in limbic and cortical regions, which undoubtedly plays a role in the physiological and emotional changes. Juvenile rats repeatedly exposed to prenatal stress (PS) exhibit behavioral features often observed in neuropsychiatric disorders including depression. However, to date the underlying neurological mechanisms are still unclear. In the current study, juvenile offspring rats whose mothers were exposed to PS were evaluated for depression-related behaviors in open field and sucrose preference test. NMDA receptor subunits NR1 and NR2A in the hippocampus, frontal cortex and striatum were assayed by western blotting. The results indicated that PS resulted in several behavioral anomalies in the OFT and sucrose preference test. Moreover, reduced levels of NMDA receptor subunits NR1 and NR2A in the hippocampus, and NR1 in prefrontal cortex and striatum of prenatally stressed juvenile offspring were found. Treatment with MK-801 to pregnant dams could prevent all those changes in the juvenile offspring. Collectivity, these data support the argument that PS to pregnant dams could induce depression-like behavior, which may be involved with abnormal expression of NR1 and NR2A in specific brain regions, and MK-801 may have antidepressant-like effects on the juvenile offspring.     

Intratumoral Hepatic Stellate Cells as a Poor Prognostic Marker and a New Treatment Target?for?Hepatocellular Carcinoma

Hepatic stellate cells (HSCs), a specialized stromal cytotype in the liver, have been demonstrated to actively contribute to hepatocellular carcinoma (HCC) development. However, the previous studies were performed using HSC cell lines, and the prognostic value of intratumoral HSCs (tHSCs) was unclear. Here we isolated tHSCs from fresh human HCC tissues, and analyzed the abilities of tHSCs to promote HCC progression by using in vitro assays for cell viability, migration and invasion as well as epithelial-mesenchymal transition (EMT) phenotype. 252 HCC patients who underwent hepatectomy were enrolled for analysis of tHSCs and E-cadherin expression in tumor tissues, and 55 HCC patients for analysis of tHSCs in tumor tissues and circulating tumor cells (CTCs) in blood. Prognostic factors were then identified. The results showed that coculture of tHSCs with HCC cells had a stronger effect on HCC cell viability, migration and invasion, accompanied with the acquisition of epithelial-mesenchymal transition (EMT) phenotype. In vivo cotransplantation of HCC cells with tHSCs into nude mice more efficiently promoted tumor formation and growth. Icaritin, a known apoptosis inducer of HSCs, was demonstrated to effectively inhibit tHSC proliferation in vitro and tHSC-induced HCC-promoting effects in vivo. Clinical evidence indicated that tHSCs were rich in 45% of the HCC specimens, tHSC-rich subtypes were negatively correlated either with E-cadherin expression in tumor tissues (r = -0.256, p < 0.001) or with preoperative CTCs in blood (r = -0.287, p = 0.033), and were significantly correlated with tumor size (p = 0.027), TNM staging (p = 0.018), and vascular invasion (p = 0.008). Overall and recurrence-free survival rates of tHSC-rich patients were significantly worse than those for tHSC-poor patients. Multivariate analysis revealed tHSC-rich as an independent factor for overall and recurrence-free survival. In conclusion, tHSCs provide a promising prognostic biomarker and a new treatment target for HCC.     

A microRNA miR-34a-Regulated Bimodal Switch Targets Notch in Colon Cancer Stem Cells

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Highlights? miR-34a regulates colon cancer stem cell asymmetric division ? miR-34a generates a sharp threshold response ? miR-34a converts Notch signaling into a toggle switch ? Binary Notch levels specify self-renewal versus differentiation     

Secreted Frizzled-Related Protein 3 Regulates Activity-Dependent Adult Hippocampal Neurogenesis

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Highlights? Wnt inhibitor sFRP3 exhibits activity-dependent expression in the adult hippocampus ? sFRP3 maintains quiescence of adult hippocampal radial glia-like neural stem cells ? sFRP3 inhibits maturation, dendritic development, and spinal formation of new neurons ? sFRP3 partially mediates activity-dependent adult hippocampal neurogenesis     

Biodegradation of Lignocellulose by White-Rot Fungi: Structural Characterization of Water-Soluble Hemicelluloses

In the biological pretreatment process, white-rot fungi are mostly used to degrade lignin and carbohydrates in lignocellulosic biomass. In this study, water-soluble hemicelluloses were recovered from birch wood (Betula alnoides) decayed by white-rot fungi (Ganoderma lucidum C7016) for different durations up to 16 weeks. Accordingly, the dimethyl sulfoxide (DMSO)-soluble hemicelluloses were isolated from the untreated birch wood as a comparison. Results showed that the fungal-degraded polysaccharides were acidic hemicelluloses having a high content of uronic acids ranging from 20.6 to 22.5 %. Gel permeation chromatography analysis demonstrated that the recovered water-soluble hemicelluloses had a lower average molecular weight (M _w, 15,990–27,560 g?mol^?1) than that of the DMSO-soluble hemicelluloses (M _w , 33,960 g?mol^?1). Fourier transform infrared spectroscopy, scanning electron microscopy, one- and two-dimensional nuclear magnetic resonance spectroscopy also revealed significantly changes between those of fungal degraded and DMSO-soluble hemicelluloses. It was proposed that the hemicelluloses with low molecular weights were easily removed from wood by fungal degradation. This research revealed the changes of hemicelluloses in fungal degradation in the natural environment, which may enable the exploration of novel methods in bioconversion of lignocellulosic biomass for the production of biofuels and biopolymers, in addition to the development of new and better ways to protect wood from biodegradation by microorganisms.     

Network-Level Structural Abnormalities of Cerebral Cortex in Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1DM) usually begins in childhood and adolescence and causes lifelong damage to several major organs including the brain. Despite increasing evidence of T1DM-induced structural deficits in cortical regions implicated in higher cognitive and emotional functions, little is known whether and how the structural connectivity between these regions is altered in the T1DM brain. Using inter-regional covariance of cortical thickness measurements from high-resolution T1-weighted magnetic resonance data, we examined the topological organizations of cortical structural networks in 81 T1DM patients and 38 healthy subjects. We found a relative absence of hierarchically high-level hubs in the prefrontal lobe of T1DM patients, which suggests ineffective top-down control of the prefrontal cortex in T1DM. Furthermore, inter-network connections between the strategic/executive control system and systems subserving other cortical functions including language and mnemonic/emotional processing were also less integrated in T1DM patients than in healthy individuals. The current results provide structural evidence for T1DM-related dysfunctional cortical organization, which specifically underlie the top-down cognitive control of language, memory, and emotion.