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FBW7 regulates HIF-1α/VEGF pathway in the IL-1β induced chondrocytes degeneration.

Thu, 06/25/2020 - 02:19
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FBW7 regulates HIF-1α/VEGF pathway in the IL-1β induced chondrocytes degeneration.

Eur Rev Med Pharmacol Sci. 2020 Jun;24(11):5914-5924

Authors: Zhu WJ, Chang BY, Wang XF, Zang YF, Zheng ZX, Zhao HJ, Cui QD

Abstract
OBJECTIVE: The aim of the study was to observe the effect of F-box/WD repeat-containing protein 7 (FBW7) on hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway in chondrocytes (CHs) under IL-1β induced degeneration.
PATIENTS AND METHODS: We explored the levels of FBW7, HIF-1α, and VEGF in degenerated cartilage from osteoarthritis (OA) and chondrocytes (CHs) treated by IL-1β. Meanwhile, we regulated HIF-1α and FBW7 expression in IL-1β treated CHs and observed the effects FBW7 of the HIF-1α/VEGF pathway.
RESULTS: FBW7 expression was significantly decreased along with the increased HIF-1α and VEGF expression both in OA cartilage and IL-1β induced degenerated CHs. Additionally, suppression of HIF-1α decreased VEGF level, which contributed to the production of collagen II, aggrecan and SOX-9, and inhibited collagen I and Runx-2 expression. Furthermore, FBW7 suppressed HIF-1α/VEGF pathway and promoted the integration of collagen II, aggrecan, and SOX-9, but inhibited the collagen I and Runx-2 expression.
CONCLUSIONS: FBW7 negatively regulates HIF-1α/VEGF pathway and plays a protective role in the IL-1β induced CHs degeneration.

PMID: 32572904 [PubMed - in process]

Higher Sensitivity and Reproducibility of Wavelet-Based Amplitude of Resting-State fMRI.

Sun, 04/19/2020 - 01:00
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Higher Sensitivity and Reproducibility of Wavelet-Based Amplitude of Resting-State fMRI.

Front Neurosci. 2020;14:224

Authors: Luo FF, Wang JB, Yuan LX, Zhou ZW, Xu H, Ma SH, Zang YF, Zhang M

Abstract
The fast Fourier transform (FFT) is a widely used algorithm used to depict the amplitude of low-frequency fluctuation (ALFF) of resting-state functional magnetic resonance imaging (RS-fMRI). Wavelet transform (WT) is more effective in representing the complex waveform due to its adaptivity to non-stationary or local features of data and many varieties of wavelet functions with different shapes being available. However, there is a paucity of RS-fMRI studies that systematically compare between the results of FFT versus WT. The present study employed five cohorts of datasets and compared the sensitivity and reproducibility of FFT-ALFF with those of Wavelet-ALFF based on five mother wavelets (namely, db2, bior4.4, morl, meyr, and sym3). In addition to the conventional frequency band of 0.0117-0.0781 Hz, a comparison was performed in sub-bands, namely, Slow-6 (0-0.0117 Hz), Slow-5 (0.0117-0.0273 Hz), Slow-4 (0.0273-0.0742 Hz), Slow-3 (0.0742-0.1992 Hz), and Slow-2 (0.1992-0.25 Hz). The results indicated that the Wavelet-ALFF of all five mother wavelets was generally more sensitive and reproducible than FFT-ALFF in all frequency bands. Specifically, in the higher frequency band Slow-2 (0.1992-0.25 Hz), the mean sensitivity of db2-ALFF results was 1.54 times that of FFT-ALFF, and the reproducibility of db2-ALFF results was 2.95 times that of FFT-ALFF. The findings suggest that wavelet-ALFF can replace FFT-ALFF, especially in the higher frequency band. Future studies should test more mother wavelets on other RS-fMRI metrics and multiple datasets.

PMID: 32300288 [PubMed]

MiR-19-3p Induces Tumor Cell Apoptosis via Targeting FAS in Rectal Cancer Cells.

Fri, 04/10/2020 - 00:51
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MiR-19-3p Induces Tumor Cell Apoptosis via Targeting FAS in Rectal Cancer Cells.

Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820917978

Authors: Su YF, Zang YF, Wang YH, Ding YL

Abstract
MicroRNAs are reported as a vital important factor in cancer cell initiation and progression processes. MicroRNA-19-3p has drawn the attention of many researchers in recent years because of its wide expression and its key role in serious kinds of tumor cells. However, the detailed mechanism of microRNA-19a-3p in these tumors is still poorly understood. So, in the present study, we aimed to explore the biological function and potential molecular mechanism of microRNA-19a-3p in different cancer cells. We first detect the relative level of miR-19a-3p in cancer cell lines and tumor tissues compared to normal cells and tissues. Results indicated the messenger RNA expression of microRNA-19a-3p existing in an aberrant low level in cancer cells and tissues. The overexpression of microRNA-19a-3p significantly reduced the cell proliferation, migration, and invasion ability in HCT116 cells. In addition to this, increased microRNA-19a-3p could induce cell apoptosis via promoting reactive oxygen species (ROS) accumulation, whereas inhibition of microRNA-19a-3p exhibited an opposite effect. Moreover, we predicated the target genes and the binding sites of microRNA-19a-3p and confirmed FAS as the targeting of microRNA-19a-3p through luciferase activity assay. Taken together, these results indicated that microRNA-19a-3p overexpression inhibited HCT116 cell proliferation, migration and invasion, induced cell apoptosis, and ROS accumulation via FAS targeting effect. It was conceivable that microRNA-19a-3p might serve as a potential molecular target for breast and liver cancer treatment.

PMID: 32266860 [PubMed - in process]

High-Frequency rTMS of the Motor Cortex Modulates Cerebellar and Widespread Activity as Revealed by SVM.

Fri, 04/10/2020 - 00:51
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High-Frequency rTMS of the Motor Cortex Modulates Cerebellar and Widespread Activity as Revealed by SVM.

Front Neurosci. 2020;14:186

Authors: Wang J, Deng XP, Wu YY, Li XL, Feng ZJ, Wang HX, Jing Y, Zhao N, Zang YF, Zhang J

Abstract
Functional magnetic resonance imaging (fMRI) studies have shown that the effect of repetitive transcranial magnetic stimulation (rTMS) can induce changes in remote brain regions. In the stimulated regions, low-frequency (≤1 Hz) rTMS induces inhibitory effects, while high-frequency (≥5 Hz) stimulation induces excitatory effects. However, these stereotypical effects arising from low- and high-frequency stimulation are based on measurements of motor evoked potentials (MEPs) induced by pulsed stimulation. To test the effects of rTMS on remote brain regions, the current study recruited 31 young healthy adults who participated in three rTMS sessions (10 Hz high frequency, 1 Hz low frequency, and sham) on three separate days. The stimulation target was based on individual fMRI activation in the motor cortex evoked by a finger movement task. Pre- and post-rTMS resting-state fMRI (RS-fMRI) were acquired. Regional homogeneity (ReHo) and degree centrality (DC) were calculated to measure the local and global connectivity, respectively. Compared with the sham session, high-frequency (10 Hz) rTMS significantly increased ReHo and DC in the right cerebellum, while low-frequency (1 Hz) stimulation did not significantly alter ReHo or DC. Then, using a newly developed PAIR support vector machine (SVM) method, we achieved accuracy of 93.18-97.24% by split-half validation for pairwise comparisons between conditions for ReHo or DC. While the univariate analyses suggest that high-frequency rTMS of the left motor cortex could affect distant brain activity in the right cerebellum, the multivariate SVM results suggest that both high- and low-frequency rTMS significantly modulated widespread brain activity. The current findings are useful for increasing the understanding of the mechanisms of rTMS, as well as guiding precise individualized rTMS treatment of movement disorders.

PMID: 32265624 [PubMed]

Reduced default mode network functional connectivity in patients with recurrent major depressive disorder.

Fri, 03/27/2020 - 00:36
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Reduced default mode network functional connectivity in patients with recurrent major depressive disorder.

Proc Natl Acad Sci U S A. 2019 04 30;116(18):9078-9083

Authors: Yan CG, Chen X, Li L, Castellanos FX, Bai TJ, Bo QJ, Cao J, Chen GM, Chen NX, Chen W, Cheng C, Cheng YQ, Cui XL, Duan J, Fang YR, Gong QY, Guo WB, Hou ZH, Hu L, Kuang L, Li F, Li KM, Li T, Liu YS, Liu ZN, Long YC, Luo QH, Meng HQ, Peng DH, Qiu HT, Qiu J, Shen YD, Shi YS, Wang CY, Wang F, Wang K, Wang L, Wang X, Wang Y, Wu XP, Wu XR, Xie CM, Xie GR, Xie HY, Xie P, Xu XF, Yang H, Yang J, Yao JS, Yao SQ, Yin YY, Yuan YG, Zhang AX, Zhang H, Zhang KR, Zhang L, Zhang ZJ, Zhou RB, Zhou YT, Zhu JJ, Zou CJ, Si TM, Zuo XN, Zhao JP, Zang YF

Abstract
Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

PMID: 30979801 [PubMed - indexed for MEDLINE]

Linked anatomical and functional brain alterations in children with attention-deficit/hyperactivity disorder.

Sun, 03/22/2020 - 00:31
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Linked anatomical and functional brain alterations in children with attention-deficit/hyperactivity disorder.

Neuroimage Clin. 2019;23:101851

Authors: Wu ZM, Llera A, Hoogman M, Cao QJ, Zwiers MP, Bralten J, An L, Sun L, Yang L, Yang BR, Zang YF, Franke B, Beckmann CF, Mennes M, Wang YF

Abstract
OBJECTIVES: Neuroimaging studies have independently demonstrated brain anatomical and functional impairments in participants with ADHD. The aim of the current study was to explore the relationship between structural and functional brain alterations in ADHD through an integrated analysis of multimodal neuroimaging data.
METHODS: We performed a multimodal analysis to integrate resting-state functional magnetic resonance imaging (MRI), structural MRI, and diffusion-weighted imaging data in a large, single-site sample of children with and without diagnosis for ADHD. The inferred subject contributions were fed into regression models to investigate the relationships between diagnosis, symptom severity, gender, and age.
RESULTS: Compared with controls, children with ADHD diagnosis showed altered white matter microstructure in widespread white matter fiber tracts as well as greater gray matter volume (GMV) in bilateral frontal regions, smaller GMV in posterior regions, and altered functional connectivity (FC) in default mode and fronto-parietal networks. Age-related growth of GMV of bilateral occipital lobe, FC in frontal regions as well as age-related decline of GMV in medial regions seen in controls appeared reversed in children with ADHD. In the whole group, higher symptom severity was related to smaller GMV in widespread regions in bilateral frontal, parietal, and temporal lobes, as well as greater GMV in intracalcarine and temporal cortices.
CONCLUSIONS: Through a multimodal analysis approach we show that structural and functional alterations in brain regions known to be altered in subjects with ADHD from unimodal studies are linked across modalities. The brain alterations were related to clinical features of ADHD, including disorder status, age, and symptom severity.

PMID: 31077980 [PubMed - indexed for MEDLINE]