BackgroundCognitive impairments are prominent in schizophrenia (SZ). Imaging studies have demonstrated that functional changes of several areas of the brain exist in SZ patients. The relationships between these two indexes are largely unexplored in SZ. The MATRICS Consensus Cognitive Battery (MCCB) was used to measure cognitive impairment in multi-dimensional cognitive fields of SZ patients. This study was conducted to explore the relationship between cognitive functional impairment and the amplitude of low-frequency fluctuation (ALFF) in SZ patients.MethodA total of 104 participants (44 SZ patients and 60 age- and gender-matched healthy controls (HC)) were recruited for this study. The MCCB was used to assess cognitive function of the participants, while brain activity was assessed using the ALFF. The relationship between the MCCB and the ALFF was investigated by using a correlation analysis.ResultsThere were significant differences between SZ patients and HC in MCCB total and domain scores as well as in ALFF results. The reduction of ALFF in the bilateral postcentral gyri and paracentral lobule in SZ patients has a negative correlation with the MCCB sub-test of symbol coding.ConclusionThese findings suggest that the reduction of ALFF in bilateral postcentral gyri and paracentral lobule may be related to cognitive impairment in SZ patients.Electronic supplementary materialThe online version of this article (10.1186/s12888-018-1992-4) contains supplementary material, which is available to authorized users.
Hypericin (Hyp) is traditionally used as an antidepressant and antiviral agent. It selectively accumulates in spheroids and is also used as a photosensitizer in the photodynamic therapy of cancer. The present study aimed to investigate the cytotoxic effect of Hyp-mediated photodynamic therapy (Hyp-PDT) on cell growth and apoptosis of K562 leukemia cells, and to examine the underlying mechanisms. Hyp-PDT was performed with different light intensities (0.1, 0.3 and 0.5 mW/cm2), different concentrations of Hyp (0, 0.2, 0.4 and 0.8 µg/ml) and different durations of irradiation (0, 2, 4 and 8 min) in order to select the optimal conditions for subsequent experiments. A concentration of 0.4 µg/ml Hyp with a 5 h drug-light interval and 4 min irradiation at 0.3 mW/cm2 light intensity was selected as the optimal conditions. The effects of Hyp-PDT on apoptosis were determined by detecting morphological changes under microscopy and by performing western blot analysis. The results revealed that Hyp-PDT suppressed cell viability in a light intensity-, dose- and irradiation duration-dependent manner. The expression levels of cleaved caspase-9, cleaved caspase-3 and phosphorylated-C-Jun N terminal kinase (JNK) l were significantly upregulated following Hyp-PDT. These results indicated that Hyp-PDT decreased cell viability and induced mitochondria-caspase-dependent apoptosis in the K562 cells through regulation of the JNK pathway. These findings suggest that Hyp-PDT may be developed as an effective treatment for leukemia.
Yap is the key effector of Hippo signaling; however, its role in embryonic stem cells (ESCs) remains controversial. Here, we identify two Yap splicing isoforms (Yap472 and Yap488), which show equal expression levels but heterogeneous distribution in ESCs. Knockout (KO) of both isoforms reduces ESC self-renewal, accelerates pluripotency exit, but arrests terminal differentiation, while overexpression of each isoform leads to the reverse phenotype. The effect of both Yap isoforms on self-renewal is Teads-dependent and mediated by c-Myc. Nonetheless, different isoforms are found to affect overlapping yet distinct genes, and confer different developmental potential to Yap-KO cells, with Yap472 exerting a more pronounced biological effect and being more essential for neuroectoderm differentiation. Constitutive activation of Yaps, particularly Yap472, dramatically upregulates p53 and Cdx2, inducing trophectoderm trans-differentiation even under self-renewal conditions. These findings reveal the combined roles of different Yap splicing isoforms and mechanisms in regulating self-renewal efficiency and differentiation potential of ESCs.
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