scholarly journals RNA sequencing and bioinformatics analysis of human lens epithelial cells in age-related cataract

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhongying Wang ◽  
Dongmei Su ◽  
Shanhe Liu ◽  
Guiqian Zheng ◽  
Gaobo Zhang ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Human Lens ◽  
Older Individuals ◽  
Disease Mechanism ◽  
Anterior Capsule ◽  
Bioinformatics Analyses ◽  
Age Related ◽  
Pathway Analyses

Abstract Background Age-related cataract (ARC) is the main cause of blindness in older individuals but its specific pathogenic mechanism is unclear. This study aimed to identify differentially expressed genes (DEGs) associated with ARC and to improve our understanding of the disease mechanism. Methods Anterior capsule samples of the human lens were collected from ARC patients and healthy controls and used for RNA sequencing to detect DEGs. Identified DEGs underwent bioinformatics analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Subsequently, reverse transcription quantitative RT-qPCR was used to validate the different expression levels of selected genes. Results A total of 698 up-regulated DEGs and 414 down-regulated DEGs were identified in ARC patients compared with controls by transcriptome analysis. Through GO and KEGG bioinformatics analysis, the functions of significantly DEGs and their possible molecular mechanisms were determined. Sequencing results were verified by RT-qPCR as being accurate and reliable. Conclusions This study identified several genes associated with ARC, which improves our knowledge of the disease mechanism.

scholarly journals Let-7c-3p Regulates Autophagy under Oxidative Stress by Targeting ATG3 in Lens Epithelial Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Ting Li ◽  
Yanhong Huang ◽  
Wenkai Zhou ◽  
Qichang Yan
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Western Blot ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Human Lens ◽  
Lens Epithelial Cells ◽  
Age Related ◽  
Spot Number ◽  
Gene Assay

Background. Oxidative stress is an important factor during age-related cataract formation. Apoptosis and autophagy induced by oxidative stress have been reported as key factors in age-related cataract. In our research, we investigated the role of let-7c-3p in the regulation of autophagy and apoptosis during the formation of age-related cataract. Material and Methods. Real-time PCR and western blot were employed to detect the expression of let-7c-3p in the tissues of age-related cataract. Human lens epithelial cells (LECs) were treated with H2O2 as an age-related cataract model. The extent of apoptosis was measured by flow cytometry and western blot. To detect autophagy, immunofluorescence was used to analyze the spot number of LC3, and western blot was used to detect the expression of LC3-II/I and ATG3. The molecular mechanisms of let-7c-3p regulating autophagy via ATG3 under oxidative stress were performed by a luciferase report gene assay and rescue experiment. Results. Downregulation of let-7c-3p was found in the age-related cataract group aged >65 years relative to the age-related cataract group aged ≤65 years. Consistently, the expression of let-7c-3p was also lower under oxidative stress. The activities of LEC apoptosis and autophagy induced by oxidative stress were inhibited by let-7c-3p. By the bioinformatics database and the luciferase reporter assay, ATG3 was found to be a direct target of let-7c-3p. Let-7c-3p reduced the ATG3-mediated autophagy level, which was induced by oxidative stress in LECs. Conclusion. Let-7c-3p inhibits autophagy by targeting ATG3 in LECs in age-related cataract.

scholarly journals Age-related changes in visual search: manipulation of colour cues based on cone contrast and opponent modulation space

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shuto Tamura ◽  
Keiko Sato
Keyword(s):  
Visual Search ◽  
Visual Attention ◽  
Reaction Times ◽  
Visual Space ◽  
Preliminary Evidence ◽  
Human Lens ◽  
Search Performance ◽  
Older Individuals ◽  
Colour Perception ◽  
Age Related

AbstractReduced retinal illuminance affects colour perception in older adults, and studies show that they exhibit deficiencies in yellow-blue (YB) discrimination. However, the influence of colour cues on the visual attention in older individuals remains unclarified. Visual attention refers to the cognitive model by which we prioritise regions within the visual space and selectively process information. The present study aimed to explore the effect of colour on visual search performance in older observers. In our experiment, younger observers wearing glasses with a filter that simulated the spectral transmittance of the aging human lens and older observers performed two types of search tasks, feature search (FS) and conjunction search (CS), under three colour conditions: red-green, YB, and luminance. Targets and distractors were designed on the basis of the Derrington–Krauskopf–Lennie colour representation. In FS tasks, reaction times changed according to colour in all groups, especially under the YB condition, regardless of the presence or absence of distractors. In CS tasks with distractors, older participants and younger participants wearing glasses showed slower responses under chromatic conditions than under the achromatic condition. These results provide preliminary evidence that, for older observers, visual search performance may be affected by impairments in chromatic colour discrimination.

scholarly journals Accumulative deamidation of human lens protein γS-crystallin leads to partially unfolded intermediates with enhanced aggregation propensity

2020 ◽  
Author(s):  
Calvin J. Vetter ◽  
David C. Thorn ◽  
Samuel G. Wheeler ◽  
Charlie Mundorff ◽  
Kate Halverson ◽  
...  
Keyword(s):  
Light Scattering ◽  
Molecular Mechanisms ◽  
Small Population ◽  
Site Directed Mutagenesis ◽  
Human Lens ◽  
Lens Protein ◽  
Triple Mutant ◽  
Age Related ◽  
Human Lenses ◽  
Partially Unfolded

AbstractAge-related cataract is a major cause of blindness worldwide. Yet, the molecular mechanisms whereby large, light scattering aggregates form is poorly understood, because of the complexity of the aggregates isolated from human lenses. The predominant proteins in the lens are structural proteins called crystallins. The γS-crystallin is heavily modified in cataractous lenses by deamidation, which introduces a negative charge at labile asparagine residues. The effects of deamidation at asparagines, N14, N76, and N143, were mimicked by replacing the asparagine with aspartate using site-directed mutagenesis. The effects of these surface deamidations on the stability, unfolding, and aggregation properties of γS were determined using dynamic light scattering, chemical and thermal-denaturation, and hydrogen-deuterium exchange with mass spectrometry. We found that a small population of all the deamidation mimics aggregated directly into large light scattering bodies with a radius greater than 10 nm that contributed 14-60% of the total scattering intensity compared to 7% for WT under the same conditions. A possible mechanism was identified under partially denaturing conditions, where deamidation led to significantly more rapid unfolding and aggregation particularly for N76D compared to WT. The triple mutant was further destabilized, reflecting the enhanced aggregation properties of N14D and N143D. Thus, the effects of deamidation were both site-specific and cumulative. αA-crystallin was ineffective at acting as a chaperone to prevent the aggregation of destabilized, deamidated γS. It is concluded that surface deamidations, while causing minimal structural disruption individually, progressively destabilize crystallin proteins, leading to their unfolding and precipitation in aged and cataractous lenses.

scholarly journals mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases

2018 ◽  
Author(s):  
Hannah E. Walters ◽  
Lynne S. Cox
Keyword(s):  
Cardiovascular Disease ◽  
Broad Spectrum ◽  
Molecular Mechanisms ◽  
Mtor Inhibitors ◽  
Chronological Age ◽  
Older Individuals ◽  
Serine Threonine Kinase ◽  
Age Related ◽  
Life Threatening ◽  
Current Therapies

Chronological age represents the greatest risk factor for many life-threatening diseases including neurodegeneration, cancer and cardiovascular disease; ageing also increases susceptibility to infectious disease. Current therapies that effectively tackle individual diseases may have little impact on the overall healthspan of older individuals, who would still be vulnerable to other age-related pathologies. However, recent progress in ageing research has highlighted the accumulation of senescent cells with chronological age as a probable underlying cause of pathological ageing. Cellular senescence is an essentially irreversible proliferation arrest mechanism that has important roles in development, wound healing and preventing cancer, but it may limit tissue function and cause widespread inflammation with age. The serine/threonine kinase mTOR is a regulatory nexus heavily implicated in both ageing and senescence. Excitingly, a growing body of research has highlighted rapamycin and other mTOR inhibitors as promising treatments for a broad spectrum of age-related pathologies, including neurodegeneration, cancer, immunosenescence, osteoporosis, rheumatoid arthritis, age-related blindness, diabetic nephropathy, muscular dystrophy, and cardiovascular disease. In this review, we assess the use of mTOR inhibitors to treat age-related pathologies, discuss possible molecular mechanisms of action where evidence is available, and consider strategies to minimize undesirable side effects. We also emphasize the urgent need for reliable, non-invasive biomarkers of senescence and biological ageing to better monitor the efficacy of any healthy ageing therapy.

scholarly journals Bioinformatics Analysis Identifying Key Biomarkers in Bladder Cancer

Data ◽  
2020 ◽  
Vol 5 (2) ◽  
pp. 38
Author(s):  
Chuan Zhang ◽  
Mandy Berndt-Paetz ◽  
Jochen Neuhaus
Keyword(s):  
Bladder Cancer ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Kegg Pathway ◽  
Tumor Stage ◽  
Hub Genes ◽  
Go Enrichment ◽  
Comprehensive Information ◽  
Pathway Analyses ◽  
Potential Biomarkers

Our goal was to find new diagnostic and prognostic biomarkers in bladder cancer (BCa), and to predict molecular mechanisms and processes involved in BCa development and progression. Notably, the data collection is an inevitable step and time-consuming work. Furthermore, identification of the complementary results and considerable literature retrieval were requested. Here, we provide detailed information of the used datasets, the study design, and on data mining. We analyzed differentially expressed genes (DEGs) in the different datasets and the most important hub genes were retrieved. We report on the meta-data information of the population, such as gender, race, tumor stage, and the expression levels of the hub genes. We include comprehensive information about the gene ontology (GO) enrichment analyses and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. We also retrieved information about the up- and down-regulation of genes. All in all, the presented datasets can be used to evaluate potential biomarkers and to predict the performance of different preclinical biomarkers in BCa.

scholarly journals Integrated bioinformatics analysis of As, Au, Cd, Pb and Cu heavy metal responsive marker genes through Arabidopsis thaliana GEO datasets

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6495 ◽  
Author(s):  
Chao Niu ◽  
Min Jiang ◽  
Na Li ◽  
Jianguo Cao ◽  
Meifang Hou ◽  
...  
Keyword(s):  
Heavy Metals ◽  
Heavy Metal ◽  
Stress Responses ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Kegg Pathway ◽  
Marker Genes ◽  
Bioinformatics Analyses ◽  
Soil And Water

Background Current environmental pollution factors, particularly the distribution and diffusion of heavy metals in soil and water, are a high risk to local environments and humans. Despite striking advances in methods to detect contaminants by a variety of chemical and physical solutions, these methods have inherent limitations such as small dimensions and very low coverage. Therefore, identifying novel contaminant biomarkers are urgently needed. Methods To better track heavy metal contaminations in soil and water, integrated bioinformatics analysis to identify biomarkers of relevant heavy metal, such as As, Cd, Pb and Cu, is a suitable method for long-term and large-scale surveys of such heavy metal pollutants. Subsequently, the accuracy and stability of the results screened were experimentally validated by quantitative PCR experiment. Results We obtained 168 differentially expressed genes (DEGs) which contained 59 up-regulated genes and 109 down-regulated genes through comparative bioinformatics analyses. Subsequently, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of these DEGs were performed, respectively. GO analyses found that these DEGs were mainly related to responses to chemicals, responses to stimulus, responses to stress, responses to abiotic stimulus, and so on. KEGG pathway analyses of DEGs were mainly involved in the protein degradation process and other biologic process, such as the phenylpropanoid biosynthesis pathways and nitrogen metabolism. Moreover, we also speculated that nine candidate core biomarker genes (namely, NILR1, PGPS1, WRKY33, BCS1, AR781, CYP81D8, NR1, EAP1 and MYB15) might be tightly correlated with the response or transport of heavy metals. Finally, experimental results displayed that these genes had the same expression trend response to different stresses as mentioned above (Cd, Pb and Cu) and no mentioned above (Zn and Cr). Conclusion In general, the identified biomarker genes could help us understand the potential molecular mechanisms or signaling pathways responsive to heavy metal stress in plants, and could be applied as marker genes to track heavy metal pollution in soil and water through detecting their expression in plants growing in those environments.

scholarly journals mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases

2018 ◽  
Vol 19 (8) ◽  
pp. 2325 ◽  
Author(s):  
Hannah Walters ◽  
Lynne Cox
Keyword(s):  
Cardiovascular Disease ◽  
Broad Spectrum ◽  
Molecular Mechanisms ◽  
Mtor Inhibitors ◽  
Chronological Age ◽  
Older Individuals ◽  
Serine Threonine Kinase ◽  
Non Invasive ◽  
Age Related ◽  
Life Threatening

Chronological age represents the greatest risk factor for many life-threatening diseases, including neurodegeneration, cancer, and cardiovascular disease; ageing also increases susceptibility to infectious disease. Current efforts to tackle individual diseases may have little impact on the overall healthspan of older individuals, who would still be vulnerable to other age-related pathologies. However, recent progress in ageing research has highlighted the accumulation of senescent cells with chronological age as a probable underlying cause of pathological ageing. Cellular senescence is an essentially irreversible proliferation arrest mechanism that has important roles in development, wound healing, and preventing cancer, but it may limit tissue function and cause widespread inflammation with age. The serine/threonine kinase mTOR (mechanistic target of rapamycin) is a regulatory nexus that is heavily implicated in both ageing and senescence. Excitingly, a growing body of research has highlighted rapamycin and other mTOR inhibitors as promising treatments for a broad spectrum of age-related pathologies, including neurodegeneration, cancer, immunosenescence, osteoporosis, rheumatoid arthritis, age-related blindness, diabetic nephropathy, muscular dystrophy, and cardiovascular disease. In this review, we assess the use of mTOR inhibitors to treat age-related pathologies, discuss possible molecular mechanisms of action where evidence is available, and consider strategies to minimize undesirable side effects. We also emphasize the urgent need for reliable, non-invasive biomarkers of senescence and biological ageing to better monitor the efficacy of any healthy ageing therapy.

scholarly journals Ghrelin Protects Human Lens Epithelial Cells against Oxidative Stress-Induced Damage

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Jie Bai ◽  
Fan Yang ◽  
Li Dong ◽  
Yi Zheng
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Human Lens ◽  
Morphological Examination ◽  
Important Mediator ◽  
Age Related ◽  
Ros Accumulation ◽  
Cellular Apoptosis ◽  
Antioxidant Supplements

Oxidative stress has been recognized as an important mediator in the pathogenesis of age-related cataracts; using antioxidant supplements is one plausible strategy to protect the antioxidative defense system against oxidative stress. Ghrelin administration is expected to reduce ROS, preventing the onset of different diseases. The role of ghrelin, if any, in protecting against oxidative stress in HLECs has never been examined. In the present study, we investigated the effects of ghrelin against H2O2-induced oxidative stress and the associated molecular mechanisms in HLECs and rat lenses. The results showed that pretreatment with ghrelin reduced H2O2-induced cellular apoptosis and ROS accumulation, increased the expression levels of SOD and CAT, and decreased the expression level of MDA. The morphological examination showed that the ghrelin-treated lens organ culture maintained transparency. This is the first report to show that ghrelin can protect HLECs from H2O2-induced oxidative stress. Our findings suggest that ghrelin may prevent the progression of cataracts, which has treatment value for ophthalmologists.

scholarly journals Identification of SRGAP2 as a Potential Oncogene and a Prognostic Biomarker in Hepatocellular Carcinoma Using Bioinformatics Analyses and Biological Experiments

2020 ◽  
Author(s):  
Yan Li ◽  
Lu Qiao ◽  
Yuru Bai ◽  
Cailan Xiao ◽  
Jian Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Rna Sequencing ◽  
High Throughput ◽  
Molecular Mechanisms ◽  
Prognostic Biomarker ◽  
Migration And Invasion ◽  
Bioinformatics Analyses ◽  
Network Analyses ◽  
Hcc Cells

Abstract Background: Hepatocellular carcinoma (HCC) is one of the common malignancies worldwide. Slit-Robo GTPase-activating proteins (SRGAPs) have been shown to regulate the occurrence and development of various tumors. However, their specific role in HCC remains elusive.Methods: The expression pattern, genetic alteration and prognostic value of SRGAPs in HCC are analyzed by bioinformatics tools. The biological functions of SRGAP2 in HCC cells are demonstrated by in vitro experiments. The high-throughput RNA sequencing is conducted to explore the underlying molecular mechanisms of SRGAP2 in HCC cells.Results: The expression levels of SRGAP1 and SRGAP2 are significantly elevated in HCC tissues compared to the normal both in Oncomine and TCGA datasets, and SRGAP2 are dramatically upregulated both in mRNA and protein levels. Moreover, higher SRGAP2 is significantly related to the clinical stages of HCC. Meanwhile, SRGAP2 might be an independent prognostic indicator, as it correlates negatively with the clinical outcomes of HCC patients. Further SRGAP2-silencing experiments imply that SRGAP2 might remarkably promote the migration and invasion of HCC cells in EMT-independent manners. Based on the high-throughput RNA sequencing of SRGAP2-knockdown HCC cells, enrichment and network analyses demonstrate that SRGAP2 is closely associated with cellular metabolic signaling.Conclusions: Our study firstly illustrates the crucial role of SRGAP2 in the metastasis of HCC and explores its underlying molecular mechanisms. We identify SRGAP2 as a promising prognostic biomarker and a novel therapeutic target for HCC patients.

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