Mitochondrial protein dysfunction in pathogenesis of neurological diseases

Mitochondria are essential organelles for neuronal function and cell survival. Besides the well-known bioenergetics, additional mitochondrial roles in calcium signaling, lipid biogenesis, regulation of reactive oxygen species, and apoptosis are pivotal in diverse cellular processes. The mitochondrial proteome encompasses about 1,500 proteins encoded by both the nuclear DNA and the maternally inherited mitochondrial DNA. Mutations in the nuclear or mitochondrial genome, or combinations of both, can result in mitochondrial protein deficiencies and mitochondrial malfunction. Therefore, mitochondrial quality control by proteins involved in various surveillance mechanisms is critical for neuronal integrity and viability. Abnormal proteins involved in mitochondrial bioenergetics, dynamics, mitophagy, import machinery, ion channels, and mitochondrial DNA maintenance have been linked to the pathogenesis of a number of neurological diseases. The goal of this review is to give an overview of these pathways and to summarize the interconnections between mitochondrial protein dysfunction and neurological diseases.Peer reviewe

Chronic Alcohol Causes Alteration of Lipidome Profiling in Brain

Much efforts have been tried to clarify the molecular mechanism of alcohol-induced brain damage from the perspective of genome and protein; however, the effect of chronic alcohol exposure on global lipid profiling of brain is unclear. In the present study, by using Q-TOF/MS-based lipidomics approach, we investigated the comprehensive lipidome profiling of brain from the rats orally administrated with alcohol daily, continuously for one year. Through systematically analysis of all lipids in prefrontal cortex (PFC) and striatum region, we found that long-term alcohol exposure profoundly modified brain lipidome profiling. Notably, three kinds of lipid classes, glycerophospholipid (GP), glycerolipid (GL) and fatty acyls (FA), were significantly increased in these two brain regions. Interestingly, most of the modified lipids were involved in synthetic pathways of endoplasmic reticulum (ER), which may result in ER stress-related metabolic disruption. Moreover, alcohol-modified lipid species displayed long length of carbon chain with high degree of unsaturation. Taken together, our results firstly present that chronic alcohol exposure markedly modifies brain lipidomic profiling, which may activate ER stress and eventually result in neurotoxicity. These findings provide a new insight into the mechanism of alcohol-related brain damage.Peer reviewe

Methamphetamine exposure drives cell cycle exit and aberrant differentiation in rat hippocampal-derived neurospheres

Introduction: Methamphetamine (METH) abuse by pregnant drug addicts causes toxic effects on fetal neurodevelopment; however, the mechanism underlying such effect of METH is poorly understood.Methods: In the present study, we applied three-dimensional (3D) neurospheres derived from the embryonic rat hippocampal tissue to investigate the effect of METH on neurodevelopment. Through the combination of whole genome transcriptional analyses, the involved cell signalings were identified and investigated.Results: We found that METH treatment for 24 h significantly and concentration-dependently reduced the size of neurospheres. Analyses of genome-wide transcriptomic profiles found that those down-regulated differentially expressed genes (DEGs) upon METH exposure were remarkably enriched in the cell cycle progression. By measuring the cell cycle and the expression of cell cycle-related checkpoint proteins, we found that METH exposure significantly elevated the percentage of G0/G1 phase and decreased the levels of the proteins involved in the G1/S transition, indicating G0/G1 cell cycle arrest. Furthermore, during the early neurodevelopment stage of neurospheres, METH caused aberrant cell differentiation both in the neurons and astrocytes, and attenuated migration ability of neurospheres accompanied by increased oxidative stress and apoptosis.Conclusion: Our findings reveal that METH induces an aberrant cell cycle arrest and neuronal differentiation, impairing the coordination of migration and differentiation of neurospheres

A rapid and nondestructive method to determine the distribution map of protein, carbohydrate and sialic acid on Edible bird’s nest by hyper-spectral imaging and chemometrics

Edible bird’s nest (EBN) is a precious functional food in Southeast Asia. A rapid and nondestructive method for determining the distribution map of protein content (PC), carbohydrate content (CC) and sialic acid content (SAC) on EBN sample was proposed. Firstly, 60 EBNs were used for hyperspectral image acquisition, and components content (PC, CC and SAC) were determined by chemical analytical methods. Secondly, the spectral signals of EBN hyperspectral image and EBN components content were used to build calibration models. Thirdly, spectra of each pixel in EBN hyperspectral image were extracted, and these spectra were substituted in the calibration models to predict the PC, CC and SAC of each pixel in the EBN image, so the visual distribution maps of PC, CC and SAC on the whole EBN were obtained. It is the first time to show the distribution tendency of PC, CC and SAC on the whole EBN sample

Research on Improved Multi-Channel Image Stitching Technology Based on Fast Algorithms

The image registration and fusion process of image stitching algorithms entails significant computational costs, and the use of robust stitching algorithms with good performance is limited in real-time applications on PCs (personal computers) and embedded systems. Fast image registration and fusion algorithms suffer from problems such as ghosting and dashed lines, resulting in suboptimal display effects on the stitching. Consequently, this study proposes a multi-channel image stitching approach based on fast image registration and fusion algorithms, which enhances the stitching effect on the basis of fast algorithms, thereby augmenting its potential for deployment in real-time applications. First, in the image registration stage, the gridded Binary Robust Invariant Scalable Keypoints (BRISK) method was used to improve the matching efficiency of feature points, and the Grid-based Motion Statistics (GMS) algorithm with a bidirectional rough matching method was used to improve the matching accuracy of feature points. Then, the optimal seam algorithm was used in the image fusion stage to obtain the seam line and construct the fusion area. The seam and transition areas were fused using the fade-in and fade-out weighting algorithm to obtain smooth and high-quality stitched images. The experimental results demonstrate the performance of our proposed method through an improvement in image registration and fusion metrics. We compared our approach with both the original algorithm and other existing methods and achieved significant improvements in eliminating stitching artifacts such as ghosting and discontinuities while maintaining the efficiency of fast algorithms

Silencing HOXC13 exerts anti-prostate cancer effects by inducing DNA damage and activating cGAS/STING/IRF3 pathway

Abstract Background Advanced prostate cancer (PCa) will develop into castration-resistant prostate cancer (CRPC) and lead to poor prognosis. As the primary subtype of CRPC, CRPC-AR accounts for the major induction of PCa heterogeneity. CRPC-AR is mainly driven by 25 transcription factors (TFs), which we speculate may be the key factors driving PCa toward CRPC. Therefore, it is necessary to clarify the key regulator and its molecular mechanism mediating PCa progression. Methods Firstly, we downloaded transcriptomic data and clinical information from TCGA-PRAD. The characteristic gene cluster was identified by PPI clustering, GO enrichment, co-expression correlation and clinical feature analyses for 25 TFs. Then, the effects of 25 TFs expression on prognosis of PCa patients was analyzed using univariate Cox regression, and the target gene was identified. The expression properties of the target gene in PCa tissues were verified using tissue microarray. Meanwhile, the related mechanistic pathway of the target gene was mined based on its function. Next, the target gene was silenced by small interfering RNAs (siRNAs) for cellular function and mechanistic pathway validation. Finally, CIBERSORT algorithm was used to analyze the infiltration levels of 22 immune cells in PCa patients with low and high expression of target gene, and validated by assaying the expression of related immunomodulatory factor. Results We found that HOX family existed independently in 25 TFs, among which HOXC10, HOXC12 and HOXC13 had unique clinical features and the PCa patients with high HOXC13 expression had the worst prognosis. In addition, HOXC13 was highly expressed in tumor tissues and correlated with Gleason score and pathological grade. In vitro experiments demonstrated that silencing HOXC13 inhibited 22RV1 and DU145 cell function by inducing cellular DNA damage and activating cGAS/STING/IRF3 pathway. Immune infiltration analysis revealed that high HOXC13 expression suppressed infiltration of γδ T cells and plasma cells and recruited M2 macrophages. Consistent with these results, silencing HOXC13 up-regulated the transcriptional expression of IFN-β, CCL2, CCL5 and CXCL10. Conclusion HOXC13 regulates PCa progression by mediating the DNA damage-induced cGAS/STING/IRF3 pathway and remodels TIME through regulation of the transcription of the immune factors IFN-β, CCL2, CCL5 and CXCL10