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Purpose. To describe both the functional and pathological alternations in neurosensory retina in a murine model of spontaneous type 2 diabetes (db/db mouse). Methods. db/db (BKS/DB−/−) mice and heterozygous littermates (as control group) at various ages (12, 16, 20, 24, and 28 weeks) were inspected with pattern electroretinogram (PERG), fundus fluorescein angiography (FFA), and optical coherence tomography (OCT). Histological markers of neuroinflammation (IBA-1 and F4/80) were evaluated by immunohistochemistry. In addition, levels of retinal ganglion cell death were measured by terminal dUTP nick-end labeling (TUNEL). Results. Significant alternations of PERG responses and increased retinal ganglion cells (RGCs) apoptosis were observed in diabetic db/db mice for 20-week period when compared with control group. IBA-1 and F4/80 expression in microglia/macrophages became evidently for 24-week period, thus supporting the PERG findings. Furthermore, obvious thinning of nasal and dorsal retina in 28-week-old db/db mice was also revealed by OCT. No visible retinal microvascular changes were detected by FFA throughout the experiments on db/db mice. Conclusions. Diabetic retina underwent neurodegenerative changes in db/db mice, which happened at retinal ganglion cell layer and inner nuclear layer. But there was no obvious abnormality in retinal vasculature on db/db mice.

The AH protein composition was significantly different between wet AMD and non-AMD patients. The proteins identified in this study may be potential biomarkers of wet AMD development and might play a role in the mechanisms of wet AMD.

BackgroundEnsemble Empirical Mode Decomposition (EEMD) has been popularised for single-channel Electromyography (EMG) signal processing as it can effectively extract the temporal information of the EMG time series. However, few papers examine the temporal and spatial characteristics across multiple muscle groups in relation to multichannel EMG signals.ExperimentThe experimental data was obtained from the Center for Machine Learning and Intelligent Systems, University of California Irvine (UCI). The data was donated by the Nueva Granada Military University and the Technopark node Manizales in Colombia. The databases of 11 male subjects from the healthy group were taken into the study. The subjects undergo three exercise programs, leg extension from a sitting position (sitting), flexion of the leg up (standing), and gait (walking), while four electrodes were placed on biceps femoris (BF), vastus medialis (VM), rectus femoris (RF), and semitendinosus (ST).MethodsBased on the experimental data, a comparative study is provided by assessing the Empirical Mode Decomposition (EMD)-based approaches, EEMD, Multivariate EMD (MEMD), and Noise-Assisted MEMD (NA-MEMD). The outcomes from these approaches are then quantitatively estimated on the basis of three criterions, the number of Intrinsic Mode Functions (IMFs), mode-alignment and mode-mixing.ResultsBoth MEMD and NA-MEMD methods (except EEMD) can guarantee equal numbers of IMFs. For mode-alignment and mode-mixing, NA-MEMD is optimal compared with MEMD and EEMD, and MEMD is merely better than EEMD.ConclusionsThis study proposes the NA-MEMD approach for multichannel EMG signal processing. This finding implies that NA-MEMD is effective for simultaneously analysing IMFs based frequency bands. It has a vital clinical implication in exploring the neuromuscular patterns that enable the multiple muscle groups to coordinate while performing the functional activities of daily living.

MicroRNA-375 is involved in many types of alimentary system cancers. Our previous studies showed that microRNA-375 was significantly down-regulated in carcinoma tissues compared with para-carcinoma tissues, which strongly indicates that microRNA-375 might suppress the occurrence and development of colorectal cancer. However, the mechanism underlying the microRNA-375 regulation in colorectal cancer remains unclear. In this study, we first sorted out jak2, map3k8 and atg7 as microRNA-375 targeted genes from multiple databases, and found that jak2, map3k8 and their downstream genes stat3 and erk were up-regulated in carcinoma tissues. Secondly, we over-expressed microRNA-375 in colorectal cancer cell lines (HCT116, Caco2 and HT29). Our results showed that in microRNA-375 over-expressing cells, JAK2/STAT3 and MAP3K8/ERK proteins were down-regulated, cell proliferation was inhibited, cell migration rate did not change. There was no significant difference on ATG7 expression between the control group and microRNA-375 over-expressing HT29/Caco2 cells, whereas microRNA-375 down-regulated ATG7 specifically in HCT116 cells. Finally, we demonstrated that expressing microRNA-375 suppressed tumor formation in nude mice. In conclusion, microRNA-375 might function as a tumor-repressive gene to inhibit cell proliferation, mainly through targeting both JAK2/STAT3 and MAP3K8/ERK signaling pathways in colorectal cancer. These findings suggest miR-375 as a promising diagnostic marker and a therapeutic drug for colorectal cancer.

Diabetic retinopathy is a heterogeneous retinal degenerative disease with the microvascular dysfunction being recognized as a hallmark of the advanced stage. In this study, we demonstrated that exosomes collected from the vitreous humor of proliferative diabetic retinopathy patients promoted proliferation, migration and tube formation ability of primary human retinal endothelial cells via its elevated miR-9-3p expression level. Müller glia cells were further recognized as the sole source of the aberrantly expressed miR-9-3p, and both in vitro and in vivo experiments validated that Müller glia-derived exosomes aggravate vascular dysfunction under high glucose. Mechanistically, exosomal miRNA-9-3p was transferred to retinal endothelial cells and bound to the sphingosine-1-phosphate receptor S1P 1 coding sequence, which subsequently activated VEGFR2 phosphorylation and internalization in the presence or absence of exogenous VEGF-A. We successfully orchestrated the dynamic crosstalk between retinal Müller glia cells and endothelial cells in pathological condition, which may provide a novel biomarker or promising therapeutic agents for the treatment of diabetic retinopathy.

Protein 4.1N is a member of protein 4.1 family and has been recognized as a potential tumor suppressor in solid tumors. Here, we aimed to investigate the role and mechanisms of 4.1N in non-small cell lung cancer (NSCLC). We confirmed that the expression level of 4.1N was inversely correlated with the metastatic properties of NSCLC cell lines and histological grade of clinical NSCLC tissues. Specific knockdown of 4.1N promoted tumor cell proliferation, migration and adhesion in vitro, and tumor growth and metastasis in mouse xenograft models. Furthermore, we identified PP1 as a novel 4.1N-interacting molecule, and the FERM domain of 4.1N mediated the interaction between 4.1N and PP1. Further, ectopic expression of 4.1N could inactivate JNK-c-Jun signaling pathway through enhancing PP1 activity and interaction between PP1 and p-JNK. Correspondingly, expression of potential downstream metastasis targets (ezrin and MMP9) and cell cycle targets (p53, p21 and p19) of JNK-c-Jun pathway were also regulated by 4.1N. Our data suggest that down-regulation of 4.1N expression is a critical step for NSCLC development and that repression of JNK-c-Jun signaling through PP1 is one of the key anti-tumor mechanisms of 4.1N.

Excessive exposure to high noise level environments has the potential to cause noise-induced hearing loss (NIHL), and cigarette smoking has also been shown to have a potential adverse effect on hearing. The aim of this study was to determine whether smoking interacts with noise in the development of hearing loss, and if so, the extent of the contribution from smoking on NIHL. A cross-sectional study was designed to assess the effect of smoking on NIHL in 517 male workers (non-smokers: N = 199; smokers: N = 318) exposed to a high-level industrial noise environment in China. Shift-long temporal waveforms of the noise that workers were exposed to for evaluation of noise exposures, and audiometric threshold measures were obtained on all selected subjects. The subjects used hearing protection devices only within the last 1-2 years. The results suggest that smoking has an adverse effect on NIHL in workers exposed to high level industrial noise, i.e., the median high frequency hearing thresholds were significantly greater in smokers than non-smokers exposed to noise for more than 10 years. This effect was observed at 4.0 and 6.0 kHz. Smoking did not have an adverse effect on NIHL in workers exposed to noise less than 10 years. Multivariate regression analysis revealed that the odds ratio (OR) for high frequency hearing loss (i.e., hearing threshold greater than 40 dB at 4.0 kHz) were 1.94 for smokers in comparison to non-smokers. The results suggest that: (1) smokers have a higher risk of developing high frequency hearing loss than non-smokers with a similar occupational noise exposure, and (2) the interaction between cigarette smoking and high-level noise exposure may be additive. There is a need to develop and analyze a larger database of workers with well-documented exposures and smoking histories for better understanding of the effect of smoking on NIHL incurred from high-level industrial noise exposures. A better understanding of the role of smoking may lead to its incorporation into hearing risk assessment for noise exposure.