ABSTRACT
BACKGROUND: Prostate cancer (PCa) is a leading cause of cancer-related death in men. Understanding the proteomic landscape associated with PCa risk can provide insights into its molecular mechanisms and pave the way for potential therapeutic interventions. METHODS: A proteome-wide Mendelian randomization (MR) analysis was employed to determine associations between genetically predicted protein concentrations in plasma and PCa risk. From an initial list of 4,364 proteins, significant associations were identified and validated. Multiple sensitivity analyses were also conducted to enhance the robustness of our findings. RESULTS: Of the 4,364 genetically predicted proteins, 308 exhibited preliminary associations with PCa risk. After rigorous statistical refinement, genetically predicted concentrations of 14 proteins showed positive associations with PCa risk, with odds ratios spanning from 1.55 (95% CI 1.28-1.87) for ATG4B to 2.67 (95% CI 1.94-3.67) for HCN1. In contrast, genetically predicted concentrations of ATG7, B2M, MSMB, and TMEM108 demonstrated inverse associations with PCa. The replication analysis further substantiated positive associations for MDH1 and LSM1, and a negative one for MSMB with PCa. A meta-analysis harmonizing primary and replication data mirrored these findings. Furthermore, the MVMR analysis pinpointed B2M and MSMB as having significant associations with PCa risk. CONCLUSION: The genetic evidence unveils a refined set of proteins associated with PCa risk. The findings underscore the potential of these proteins as molecular markers or therapeutic targets for PCa, calling for deeper mechanistic studies and exploration into their translational relevance.
Subject(s)
Blood Proteins , Mendelian Randomization Analysis , Prostatic Neoplasms , Humans , Prostatic Neoplasms/genetics , Prostatic Neoplasms/blood , Male , Blood Proteins/genetics , Autophagy-Related Protein 7/genetics , Genetic Predisposition to Disease , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Proteomics/methods , Risk Factors , Membrane Proteins/genetics , Membrane Proteins/blood , Polymorphism, Single Nucleotide , Prostatic Secretory ProteinsABSTRACT
Taking the AquaCrop crop model as the research object, considering the complexity and uncertainty of the crop growth process, the crop model can only achieve more accurate simulation on a single point scale. In order to improve the application scale of the crop model, this study inverted the canopy coverage of a tea garden based on UAV multispectral technology, adopted the particle swarm optimization algorithm to assimilate the canopy coverage and crop model, constructed the AquaCrop-PSO assimilation model, and compared the canopy coverage and yield simulation results with the localized model simulation results. It is found that there is a significant regression relationship between all vegetation indices and canopy coverage. Among the single vegetation index regression models, the logarithmic model constructed by OSAVI has the highest inversion accuracy, with an R2 of 0.855 and RMSE of 5.75. The tea yield was simulated by the AquaCrop-PSO model and the measured values of R2 and RMSE were 0.927 and 0.12, respectively. The canopy coverage R2 of each simulated growth period basically exceeded 0.9, and the accuracy of the simulation results was improved by about 19.8% compared with that of the localized model. The results show that the accuracy of crop model simulation can be improved effectively by retrieving crop parameters and assimilating crop models through UAV remote sensing.
ABSTRACT
Electrolyte additive engineering is a crucial method for enhancing the performance of aqueous zinc-ion batteries (AZIBs). Recently, most research predominantly focuses on the role of functional groups in regulating electrolytes, often overlooking the impact of molecule stereoscopic configuration. Herein, two isomeric sugar alcohols, mannitol and sorbitol, are employed as electrolyte additives to investigate the impact of the stereoscopic configuration of additives on the ZnSO4 electrolyte. Experimental analysis and theoretical calculations reveal that the primary factor for improving Zn anode performance is the regulation of the solvation sheath by these additives. Among the isomers, mannitol exhibits stronger binding energies with Zn2+ ions and water molecules due to its more suitable stereoscopic configuration. These enhanced bindings allow mannitol to coordinate with Zn2+, contributing to solvation structure formation and reducing the active H2O molecules in the bulk electrolyte, resulting in suppressed parasitic reactions and inhibited dendritic growth. As a result, the zinc electrodes in mannitol-modified electrolyte exhibit excellent cycling stability of 1600 h at 1 mA cm-2 and 900 h at 10 mA cm-2, respectively. Hence, this study provides novel insights into the importance of suitable stereoscopic molecule configurations in the design of electrolyte additives for highly reversible and high-rate Zn anodes.
ABSTRACT
Amyloid-ß1-42 (Aß1-42 ) is strongly associated with Alzheimer's disease (AD). The aim of this study is to elucidate whether and how miR-6076 participates in the modulation of amyloid-ß (Aß)-induced neuronal damage. To construct the neuronal damage model, SH-SY5Y cells were treated with Aß1-42 . By qRT-PCR, we found that miR-6076 is significantly upregulated in Aß1-42 -treated SH-SY5Y cells. After miR-6076 inhibition, p-Tau and apoptosis levels were downregulated, and cell viability was increased. Through online bioinformatics analysis, we found that B-cell lymphoma 6 (BCL6) was a directly target of miR-6076 via dual-luciferase reporter assay. BCL6 overexpression mediated the decrease in elevated p-Tau levels and increased viability in SH-SY5Y cells following Aß1-42 treatment. Our results suggest that down-regulation of miR-6076 could attenuate Aß1-42 -induced neuronal damage by targeting BCL6, which provided a possible target to pursue for prevention and treatment of Aß-induced neuronal damage in AD.
Subject(s)
Alzheimer Disease , MicroRNAs , Neuroblastoma , Humans , MicroRNAs/genetics , Cell Line, Tumor , Amyloid beta-Peptides/toxicity , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Apoptosis/genetics , Peptide Fragments/pharmacology , Proto-Oncogene Proteins c-bcl-6/geneticsABSTRACT
Fucoxanthin and fatty acids are active substances that are beneficial to the growth and immunity of humans and aquatic animals. However, relatively few species have been exploited for fucoxanthin and fatty acids in the industry. At the same time, due to its low extract content, poor stability, high production cost, and serious seasonal and regional limitations, the industry cannot normally meet the greater demand of the international market. Therefore, this experiment seeks to improve the fucoxanthin and fatty acid content of C. weissflogii by adjusting the nitrogen concentration in the culture medium. It was found that when the nitrogen concentration was 150 mg L-1, the cell number was 1.5 × 106 cell mL-1, and the average biomass was 0.75 g L-1. The mean value of carotenoid concentration was 2.179 mg L-1. The average concentration of fucoxanthin was 1.547 mg g-1. When the nitrogen concentration was 75 mg L-1, the fatty acid content reached its highest. By adjusting the concentration of nitrogen, the contents of fucoxanthin and fatty acids were increased. The results provided a theoretical basis for commercial extraction of fucoxanthin and fatty acids and further promoted the industrialization of fucoxanthin and fatty acids.
Subject(s)
Diatoms , Fatty Acids , Animals , Humans , Fatty Acids/pharmacology , Xanthophylls/pharmacology , Carotenoids/pharmacology , Nitrogen/pharmacologyABSTRACT
Exosomes transfer signaling molecules such as proteins, lipids, and RNAs to facilitate cell-cell communication and play an important role in the stem cell microenvironment. In previous work, we demonstrated that rat fimbria-fornix transection (FFT) enhances neurogenesis from neural stem cells (NSCs) in the subgranular zone (SGZ). However, how neurogenesis is modulated after denervation remains unknown. Here, we investigated whether exosomes in a denervated hippocampal niche may affect neurogenesis. Using the FFT rat model, we extracted hippocampal exosomes and identified them using western blots, transmission electron microscopy (TEM), and nanoparticle size measurement. We also used RNA sequencing and bioinformatic analysis of exosomes to identify noncoding RNA expression profiles and neurogenesis-related miRNAs, respectively. RNA sequencing analysis demonstrated 9 upregulated and 15 downregulated miRNAs. miR-3559-3P and miR-6324 increased gradually after FFT. Thus, we investigated the function of miR-3559-3P and miR-6324 with NSC proliferation and differentiation assays. Transfection of miR-3559-3p and miR-6324 mimics inhibited the proliferation of NSCs and promoted the differentiation of NSCs into neurons, while miR-3559-3p and miR-6324 inhibitors promoted NSC proliferation and inhibited neuronal differentiation. Additionally, the exosome marker molecules CD9, CD63, and Alix were expressed in exosomes extracted from the hippocampal niche. Finally, TEM showed that exosomes were â¼100 nm in diameter and had a "saucer-like" bilayer membrane structure. Taken together, these findings suggest that differentially expressed exosomes and their related miRNAs in the denervated hippocampal niche can promote differentiation of NSCs into neurons.
Subject(s)
Exosomes/metabolism , Hippocampus/physiology , Neural Stem Cells/cytology , Neurogenesis , Animals , Female , Fornix, Brain/surgery , Hippocampus/cytology , Male , Rats , Rats, Sprague-DawleyABSTRACT
Globally, the incidence rate for breast cancer ranks first. Treatment for early-stage breast cancer is highly cost effective. Five-year survival rate for stage 0-2 breast cancer exceeds 90%. Screening mammography has been acknowledged as the most reliable way to diagnose breast cancer at an early stage. Taiwan government has been urging women without any symptoms, aged between 45 and 69, to have a screening mammogram bi-yearly. This brings about a large workload for radiologists. In light of this, this paper presents a deep neural network (DNN)-based model as an efficient and reliable tool to assist radiologists with mammographic interpretation. For the first time in the literature, mammograms are completely classified into BI-RADS categories 0, 1, 2, 3, 4A, 4B, 4C and 5. The proposed model was trained using block-based images segmented from a mammogram dataset of our own. A block-based image was applied to the model as an input, and a BI-RADS category was predicted as an output. At the end of this paper, the outperformance of this work is demonstrated by an overall accuracy of 94.22%, an average sensitivity of 95.31%, an average specificity of 99.15% and an area under curve (AUC) of 0.9723. When applied to breast cancer screening for Asian women who are more likely to have dense breasts, this model is expected to give a higher accuracy than others in the literature, since it was trained using mammograms taken from Taiwanese women.
Subject(s)
Breast Neoplasms , Mammography , Aged , Area Under Curve , Breast Neoplasms/diagnostic imaging , Early Detection of Cancer , Female , Humans , Middle Aged , Neural Networks, ComputerABSTRACT
Taiwan faces challenges in providing long-term family care as its population rapidly ages. This study aimed to construct a health application that could effectively meet family caregivers' needs in providing home care. Mixed methods were adopted to explore their acceptance of the application, as well as to gather their suggestions for improving the application. A nonrandomized controlled group pretest-posttest design was utilized. The participants were family caregivers who were recruited via purposive sampling at a regional hospital in Taipei, Taiwan. The caregivers used the application to monitor and manage the health of those they were caring for. Elderly family caregivers scored 1.57 and 1.16 points higher than their middle-aged counterparts in terms of performance expectancy (0.61-2.53, P = .01) and effort expectancy (0.25-2.06, P = .01), respectively. The caregivers opined that it was convenient to use the application for managing the health data of their patients, and resources and solutions for overcoming problems when using the application were easily within their reach. They also suggested that relevant information for promoting patient mental health could also be included in the application. Thus, the software is acceptable to all the family caregivers regardless of age, indicating that it can assist family caregivers in the future in performing home care management.
Subject(s)
Home Care Services , Mobile Applications , Aged , Caregivers , Family , Humans , Mental Health , Middle Aged , TechnologyABSTRACT
Establishment of symbiosis between legumes and nitrogen-fixing rhizobia depends on bacterial Nod factors (NFs) that trigger symbiosis-related NF signaling in host plants. NFs are modified oligosaccharides of chitin with a fatty acid moiety. NFs can be cleaved and inactivated by host enzymes, such as MtNFH1 (MEDICAGO TRUNCATULA NOD FACTOR HYDROLASE1). In contrast to related chitinases, MtNFH1 hydrolyzes neither chitin nor chitin fragments, indicating a high cleavage preference for NFs. Here, we provide evidence for a role of MtNFH1 in the symbiosis with Sinorhizobium meliloti Upon rhizobial inoculation, MtNFH1 accumulated at the curled tip of root hairs, in the so-called infection chamber. Mutant analysis revealed that lack of MtNFH1 delayed rhizobial root hair infection, suggesting that excess amounts of NFs negatively affect the initiation of infection threads. MtNFH1 deficiency resulted in nodule hypertrophy and abnormal nodule branching of young nodules. Nodule branching was also stimulated in plants expressing MtNFH1 driven by a tandem CaMV 35S promoter and plants inoculated by a NF-overproducing S. meliloti strain. We suggest that fine-tuning of NF levels by MtNFH1 is necessary for optimal root hair infection as well as for NF-regulated growth of mature nodules.
Subject(s)
Gene Expression Regulation, Plant , Hydrolases/metabolism , Medicago truncatula/enzymology , Signal Transduction , Sinorhizobium meliloti/physiology , Symbiosis , Chitin/metabolism , Hydrolases/genetics , Medicago truncatula/genetics , Medicago truncatula/microbiology , Oligosaccharides/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Root Nodules, Plant/enzymology , Root Nodules, Plant/genetics , Root Nodules, Plant/microbiologyABSTRACT
BACKGROUND: Alzheimer's disease (AD) is a fatal neurodegenerative disorder, and the lesions originate in the entorhinal cortex (EC) and hippocampus (HIP) at the early stage of AD progression. Gaining insight into the molecular mechanisms underlying AD is critical for the diagnosis and treatment of this disorder. Recent discoveries have uncovered the essential roles of microRNAs (miRNAs) in aging and have identified the potential of miRNAs serving as biomarkers in AD diagnosis. METHODS: We sought to apply bioinformatics tools to investigate microarray profiles and characterize differentially expressed genes (DEGs) in both EC and HIP and identify specific candidate genes and pathways that might be implicated in AD for further analysis. Furthermore, we considered that DEGs might be dysregulated by miRNAs. Therefore, we investigated patients with AD and healthy controls by studying the gene profiling of their brain and blood samples to identify AD-related DEGs, differentially expressed miRNAs (DEmiRNAs), along with gene ontology (GO) analysis, KEGG pathway analysis, and construction of an AD-specific miRNA-mRNA interaction network. RESULTS: Our analysis identified 10 key hub genes in the EC and HIP of patients with AD, and these hub genes were focused on energy metabolism, suggesting that metabolic dyshomeostasis contributed to the progression of the early AD pathology. Moreover, after the construction of an miRNA-mRNA network, we identified 9 blood-related DEmiRNAs, which regulated 10 target genes in the KEGG pathway. CONCLUSIONS: Our findings indicated these DEmiRNAs having the potential to act as diagnostic biomarkers at an early stage of AD.
Subject(s)
Alzheimer Disease/genetics , Entorhinal Cortex/metabolism , Hippocampus/metabolism , MicroRNAs/genetics , RNA, Messenger/genetics , Aged , Aged, 80 and over , Biomarkers/blood , Computational Biology , Female , Gene Expression Profiling , Gene Ontology , Humans , Male , Protein Interaction MapsABSTRACT
Aerobic fermentation composting can transform solid organic waste into biological organic fertiliser, while reducing resource wastage and ecological damage. However, in the composting process, a serious loss of nitrogen occurs, primarily in the form of the release of ammonia gas. The release of ammonia gas not only pollutes the environment, but also diminishes the presence of nutrient elements, resulting in compost products that are lower in quality. Given that many factors influence the release of ammonia gas during the aerobic fermentation process, it is difficult to determine optimal process parameters. In an effort to address this issue, we propose herein a combinational weighting method based on the analytic hierarchy process (AHP) and entropy weighting method to determine the weight of each secondary index. We also establish a parametric optimisation model based on the ammonia release conditions of the ELECTRE-I method that provides a theoretical underpinning and a decision basis for optimising the process parameters that mediate the release of ammonia during the aerobic fermentation process. This method can be widely employed to reduce the release of ammonia gas and may be of significance to the future development of bioengineering-based composting technology.
Subject(s)
Bioengineering/methods , Fermentation , Refuse Disposal/methods , Air Pollutants , Ammonia , Biotechnology/methods , Composting , Gases , Industrial Microbiology/methods , Nitrogen/chemistry , Soil , Solid WasteABSTRACT
Radiotherapy (RT) as one of the most powerful cancer treatment strategies has been greatly restricted by tumor hypoxia. A mounting effort has been devoted to develop oxygen delivery systems for boosting the RT effect. Unluckily, those systems only supplied modest oxygen, which could not afford more than once and long-time RT. Herein, we describe the development of a glucose-regulated drug release platform, allowing for a long-term tumor normoxic microenvironment and repeated RT for a long time. The repeated cycles resulted in sustained high Endostar plasma levels, which dramatically normalized the tumor vasculature and chronically reversed tumor hypoxia. Taking advantage of the inexhaustible supply of oxygen, Endo@GOx-ER enabled RT achieved an impressive cancer treatment output. To the best of our knowledge, our strategy is the initial attempt to overcome tumor-hypoxia-limited RT through the normalization of tumor vasculature by using an erythrocyte-inspired and glucose-activatable platform and it visually casts a light on the clinical development.
Subject(s)
Glucose , Hypoxia , Tumor Hypoxia , Humans , Oxygen , Radiotherapy , Tumor MicroenvironmentABSTRACT
BACKGROUND: The long noncoding RNA (lncRNA) OTUD6B antisense RNA 1 (OTUD6B-AS1) is oriented in an antisense direction to the protein-coding gene OTUD6B on the opposite DNA strand. TCGA database data show that the expression of the lncRNA OTUD6B-AS1 is downregulated and that OTUD6B-AS1 acts as an antioncogene in a variety of tumors. However, the expression and biological functions of the lncRNA OTUD6B-AS1 are still unknown in tumors, including clear cell renal cell carcinoma (ccRCC). METHODS: The expression level of OTUD6B-AS1 was measured in 75 paired human ccRCC tissue and corresponding adjacent normal renal tissue samples. The correlations between the OTUD6B-AS1 expression level and clinicopathological features were evaluated using the chi-square test. The effects of OTUD6B-AS1 on ccRCC cells were determined via MTT assay, clone formation assay, transwell assay, and flow cytometry. Furthermore, the impact of OTUD6B-AS1 overexpression on the activation of the Wnt/ß-catenin signaling pathway was investigated. Finally, ACHN cells with OTUD6B-AS1 overexpression were subcutaneously injected into nude mice to evaluate the influence of OTUD6B-AS1 on tumor growth in vivo. RESULTS: In this study, we found that the expression of the lncRNA OTUD6B-AS1 was downregulated in ccRCC tissue samples and that patients with low OTUD6B-AS1 expression had shorter overall survival than patients with high OTUD6B-AS1 expression, which showed that the different expression level of OTUD6B-AS1 indirectly correlated with survival of patients. Lentivirus-mediated OTUD6B-AS1 overexpression significantly decreased the proliferation of ccRCC cells and promoted the apoptosis of the cells. Furthermore, OTUD6B-AS1 overexpression partly inhibited cell migration and invasion. The overexpression of OTUD6B-AS1 decreased the activity of the Wnt/ß-catenin pathway and suppressed the expression of epithelial-to-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Snail) in ccRCC cells. In addition, compared with the parental ACHN cells, OTUD6B-AS1-overexpressing ACHN cells injected into nude mice exhibited decreased tumor growth in vivo. CONCLUSIONS: Taken together, our findings present a road map for targeting the newly identified lncRNA OTUD6B-AS1 to suppress ccRCC progression in cell lines, and these results elucidate a novel potential therapeutic target for ccRCC treatment.
Subject(s)
Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Cell Proliferation/genetics , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , RNA, Long Noncoding/genetics , Wnt Signaling Pathway/genetics , beta Catenin/genetics , Animals , Apoptosis/genetics , Carcinogenesis/genetics , Cell Line, Tumor , Cell Movement/genetics , Disease Progression , Down-Regulation , Epithelial-Mesenchymal Transition/genetics , Female , Humans , Mice , Mice, Nude , PrognosisABSTRACT
Neural stem cells (NSCs) possess self-renewal and multilineage differentiation ability, thus are considered to be a potential source for cell replacement therapy of many nervous system diseases, such as neurodegenerative diseases. Valproate (VPA), a member of histone deacetylase inhibitor family, is an epigenetic regulator and can promote NSCs to differentiate into neurons, nevertheless, the underlying mechanisms of the process remain unclear. MicroRNAs (miRNAs) exert a crucial part in the posttranscriptional regulation of gene expression. Epigenetic mechanisms involve in the regulation of miRNAs expression. Therefore we speculated that miRNAs may be important factors during the promotion of neuronal differentiation by VPA. Here, after selecting appropriate concentration and treatment time of VPA, we conducted microRNA arrays at 24 h on the treatment of 1 mM VPA or vehicle. After validation, we obtained 5 significantly upregulated miRNAs (miR-29a-5p, miR-674-5p, miR-155-5p, miR-652-3p, and miR-210-3p) in VPA group compared with control. We predicted the target genes of these miRNAs on the website. Through gene ontology (GO) and pathway analyses, we obtained preliminary comprehension of the function of these genes. The bioinformatics analyses indicated the involvement of them during neurogenesis. In addition, we observed high expression of miR-210-3p, miR-29a-5p, and miR-674-5p in central nervous system, which suggested that they were likely to play crucial roles in neuronal differentiation. We then defined the upregulation of Map2 by transfecting mimic of miR-674-5p, which indicated the promotion of miR-674-5p on NSCs differentiation. The present study explored the miRNAs potentially mediated the function of VPA on promoting NSCs to differentiate into neurons.
Subject(s)
Anticonvulsants/pharmacology , Gene Expression Profiling , Gene Expression Regulation/drug effects , MicroRNAs/genetics , Neural Stem Cells/metabolism , Valproic Acid/pharmacology , Animals , Cell Differentiation , Cells, Cultured , Female , Neural Stem Cells/cytology , Neural Stem Cells/drug effects , Neurogenesis , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To investigate the familial risk of appendicitis in the general population. STUDY DESIGN: A nationwide, cross-sectional study consisting of 24 349 599 Taiwan National Health Insurance beneficiaries in 2015 was conducted. Among them, 788 042 individuals had at least 1 first-degree relative with appendicitis. The familial relative risks (RRs) of appendicitis and familial transmission were estimated. RESULTS: The overall RR (95% CI) of appendicitis in individuals with any affected first-degree relatives was 1.67 (1.64-1.71) compared with the general population. The RRs for individuals with an affected twin, sibling, offspring, and parent were 3.40 (2.66-4.35), 1.98 (1.92-2.04), 1.55 (1.51-1.59), and 1.54 (1.50-1.58), respectively. The RRs for individuals with 1, 2, 3 or more affected first-degree relatives were 1.65 (1.62-1.68), 2.63 (2.37-2.91), and 6.70 (4.22-10.63), respectively. Furthermore, there was an age-dependent trend of the RRs, with the greatest RR in the youngest group. The estimated familial transmission (genetic plus shared environmental contribution to the total phenotypic variance of appendicitis) was 23.2%. CONCLUSION: Individuals with a family history of appendicitis have an increased risk of appendicitis. This risk is age-dependent and related to the genetic distance and numbers of affected relatives.
Subject(s)
Appendicitis/diagnosis , Appendicitis/genetics , Genetic Predisposition to Disease , Adolescent , Adult , Aged , Child , Child, Preschool , Cross-Sectional Studies , Family Health , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Proportional Hazards Models , Registries , Risk Factors , Taiwan/epidemiology , Young AdultABSTRACT
Docosahexaenoic acid (DHA) is an n-3 long chain polyunsaturated fatty acid (PUFA) that is involved in a wide range of cellular processes in human cells. Brain lipid binding protein (BLBP) exhibits a high affinity for n-3 PUFAs, especially DHA, but the precise functional contributions of DHA and BLBP in astrocytes are not clear. We analyzed cell viability and the ratio of Ki67 positive cells after manipulating DHA and/or BLBP levels in cultured astrocytes, and found that low-dose DHA stimulated proliferation of astrocytes, whereas this proliferative effect could be attenuated by downregulation of BLBP. Moreover, we found that astrocyte proliferation was directly regulated by BLBP independently of DHA. Taken together, low-dose DHA-induced astrocyte proliferation was disturbed by insufficient BLBP; and besides acting as a fatty acid transporter, BLBP was also involved in the proliferation of astrocytes directly.
Subject(s)
Astrocytes/cytology , Astrocytes/drug effects , Docosahexaenoic Acids/pharmacology , Fatty Acid-Binding Protein 7/genetics , Gene Expression Regulation/drug effects , Animals , Astrocytes/metabolism , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Rats , Rats, Sprague-Dawley , S Phase/drug effectsABSTRACT
BACKGROUND: Stroke is a severe neurologic complication of dengue fever, described in only a few case reports. The incidence and risk factors for stroke in patients with dengue remain unclear. We conducted a population-based retrospective cohort study to investigate the risk of stroke in patients with dengue. METHODS: Using data from the Taiwan National Health Insurance Research Database, we included a total of 13 787 patients with dengue newly diagnosed between 2000 and 2012. The control cohort consisted of patients who did not have dengue, matched 1:1 by demographic characteristics and stroke-related comorbidities. We calculated the cumulative incidences and hazard ratios (HRs) of stroke in both cohorts using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: The overall incidence rate of stroke was 5.33 per 1000 person-years in the dengue cohort and 3.72 per 1000 person-years in the control cohort, with an adjusted HR of 1.16 (95% confidence interval [CI] 1.01-1.32). The risk of stroke among patients with dengue was highest in the first 2 months after diagnosis (25.53 per 1000 person-years, adjusted HR 2.49, 95% CI 1.48-4.18). INTERPRETATION: Dengue fever was associated with an increased risk of stroke in the first few months after diagnosis. The effect of dengue on stroke may be acute rather than chronic.
Subject(s)
Dengue/complications , Stroke/etiology , Adult , Aged , Cohort Studies , Dengue/epidemiology , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Assessment/methods , Risk Factors , Stroke/epidemiology , Taiwan/epidemiologyABSTRACT
BACKGROUND: The denervated hippocampus provides a proper microenvironment for the survival and neuronal differentiation of neural progenitors. While thousands of lncRNAs were identified, only a few lncRNAs that regulate neurogenesis in the hippocampus are reported. The present study aimed to perform microarray expression profiling to identify long noncoding RNAs (lncRNAs) that might participate in the hippocampal neurogenesis, and investigate the potential roles of identified lncRNAs in the hippocampal neurogenesis. RESULTS: In this study, the profiling suggested that 74 activated and 29 repressed (|log fold-change|>1.5) lncRNAs were differentially expressed between the denervated and the normal hippocampi. Furthermore, differentially expressed lncRNAs associated with neurogenesis were found. According to the tissue-specific expression profiles, and a novel lncRNA (lncRNA2393) was identified as a neural regulator in the hippocampus in this study. The expression of lncRNA2393 was activated in the denervated hippocampus. FISH showed lncRNA2393 specially existed in the subgranular zone of the dentate gyrus in the hippocampus and in the cytoplasm of neural stem cells (NSCs). The knockdown of lncRNA2393 depletes the EdU-positive NSCs. Besides, the increased expression of lncRNA2393 was found to be triggered by the change in the microenvironment. CONCLUSION: We concluded that expression changes of lncRNAs exists in the microenvironment of denervated hippocampus, of which promotes hippocampal neurogenesis. The identified lncRNA lncRNA2393 expressed in neural stem cells, located in the subgranular zone of the dentate gyrus, which can promote NSCs proliferation in vitro. Therefore, the question is exactly which part of the denervated hippocampus induced the expression of lncRNA2393. Further studies should aim to explore the exact molecular mechanism behind the expression of lncRNA2393 in the hippocampus, to lay the foundation for the clinical application of NSCs in treating diseases of the central nervous system.
Subject(s)
Hippocampus/metabolism , Neurogenesis/genetics , RNA, Long Noncoding/genetics , Animals , Cell Differentiation/genetics , Cell Proliferation , Cluster Analysis , Denervation , Female , Gene Expression Profiling , Gene Silencing , Male , Neural Stem Cells/cytology , Neural Stem Cells/metabolism , Rats , Reproducibility of Results , TranscriptomeABSTRACT
BACKGROUND/AIMS: MiR-30a-5p, a member of the microRNA-30 family (miR-30), is known to function as a tumor suppressor in several different cancers. However, the expression levels, biological function, and underlying mechanisms of miR-30a-5p in renal cell carcinoma (RCC) remain unclear. Glucose-regulated protein78 (GRP78) is a common cancer biomarker and promotes the growth and survival of cancer cells. The expression of GRP78 has been reported to be modulated by miR-30a in neurons. In this study, the expression profile of miR-30a-5p in clear cell renal cell carcinoma (ccRCC) and its effect on ccRCC through regulating GRP78 expression was investigated. METHODS: MiR-30a-5p expression was analyzed using bioinformatic software on open microarray datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and confirmed by quantitative RT-PCR (qRT-PCR) in ccRCC cell lines. Cell proliferation was investigated using CCK-8 and cell count assays. Western blotting, immunohistochemistry, luciferase reporter assays, and flow cytometry were employed to investigate the mechanisms of the effect of miR-30a-5p on ccRCC Results: MiR-30a-5p was down-regulated in ccRCC and related to the clinicopathological factors and prognosis of ccRCC. MiR-30a-5p was found to both suppress the growth of ccRCC cells and promote apoptosis of ccRCC cells in vitro. GRP78 was the direct target gene of miR-30a-5p, and the GRP78 expression was inversely correlated with the expression of miR-30a-5p in vivo and in vitro. The functional studies of GRP78 overexpression or knockdown demonstrated that GRP78 promoted proliferation and anti-apoptosis of ccRCC cells, and the oncogenic activity of GRP78 resulting in by miR-30a-5p overexpression. CONCLUSION: MiR-30a-5p is a bona fide negative regulator of GRP78 expression, and the anti-tumor activity of miR-30a-5p in ccRCC is due at least in part to down-regulating GRP78 expression and modulating the unfolded protein response (UPR) pathway. Thus, miR-30-GRP78 interaction provides a novel therapeutic candidate target in ccRCC treatment.
Subject(s)
Carcinoma, Renal Cell/pathology , Heat-Shock Proteins/metabolism , Kidney Neoplasms/pathology , MicroRNAs/metabolism , 3' Untranslated Regions , Aged , Antagomirs/metabolism , Apoptosis , Base Sequence , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/mortality , Cell Line, Tumor , Cell Movement , Cell Proliferation , Databases, Genetic , Down-Regulation , Endoplasmic Reticulum Chaperone BiP , Female , Heat-Shock Proteins/antagonists & inhibitors , Heat-Shock Proteins/genetics , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Kidney Neoplasms/metabolism , Kidney Neoplasms/mortality , Male , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , Middle Aged , Prognosis , RNA Interference , RNA, Small Interfering/metabolism , Sequence AlignmentABSTRACT
We report the properties of dual phononic-photonic band gaps and localized modes of eightfold lithium niobate (LiNbO3) phoxonic quasicrystals (PhXQCs). Complete and large phoxonic band gaps are easily achieved despite the low refractive index of LiNbO3 substrate. Point defect intentionally introduced can form localized modes within both forbidden and transparency bands over a wide range of geometric parameters. Further analysis indicates that the localized modes within transparency bands originate from the intrinsic high-order rotational symmetry of quasiperiodic structures, which resemble whispering gallery modes. LiNbO3 PhXQCs provide a good candidate to enhance phononic-photonic interaction and show considerable advantage over the periodic counterparts.