ABSTRACT
Atherosclerosis (AS) is a common cardiovascular disease and remains the leading cause of death in the world. It is generally believed that the deposition of foam cells in the arterial wall is the main cause of AS. Moreover, promoting cholesterol efflux and enhancing the ability of reverse cholesterol transport (RCT) can effectively inhibit the formation of foam cells, thereby preventing the occurrence and development of AS. Astaxanthin, with a powerful antioxidant ability, has a potential role in the prevention of atherosclerosis, but how it works in preventing atherosclerosis remains unknown. Here, our experimental results suggest that astaxanthin can upregulate the expression of circular RNA tripeptidyl-peptidase II (circTPP2) and eventually promote cholesterol efflux by modulating ATP-binding cassette subfamily A member 1 (ABCA1). The expression of ABCA1 was significantly suppressed after knocking down circTPP2 in macrophage-derived foam cells. In addition, the experimental results showed that circTPP2 could downregulate the expression of microRNA-3073b-5p (miR-3073b-5p), and ABCA1 was identified as the target gene of miR-3073b-5p. In conclusion, the circTPP2/miR-3073b-5p/ABCA1 axis may be the specific mechanism of astaxanthin promoting cholesterol efflux.
Subject(s)
Atherosclerosis , MicroRNAs , Animals , Mice , Foam Cells/metabolism , MicroRNAs/genetics , Cholesterol/metabolism , RAW 264.7 Cells , Atherosclerosis/metabolism , Cholesterol, LDL/metabolism , ATP Binding Cassette Transporter 1/metabolismABSTRACT
Background: A growing body of literature has demonstrated that circular RNAs (circRNAs) are the potential biomarkers in human cardiovascular disease (CVD). Therefore, a meta-analysis based on current studies was accomplished to appraise the role of circRNAs in the diagnostic of CVD patients. Methods: Studies before October 30, 2021, were searched using PubMed, EMBASE, the Web of Science, and Cochrane Library. The diagnostic odds ratio (DOR) with a confidence interval (CI) of 95% was used to investigate the associations between circRNAs and CVDs. Results: A total of 27 eligible articles were selected, including 47 studies, with 6833 participants meeting the criteria standard constrain. The pooled overall sensitivity and specificity for circRNAs expression profile in differentiating CVD patients from controls (non-CVDs or healthy subjects) were 0.81 (95%CI 0.78-0.83) and 0.74 (95%CI 0.68-0.78), respectively; the overall positive likelihood ratio was 3.1 (95%CI 2.5-3.7); the negative likelihood ratio was 0.26 (95%CI 0.22-0.31); the overall diagnostic odds ratio corresponding to an area under the curve of 0.85 (95%CI 0.81-0.88) was 12 (95%CI 9-16). Subgroup analysis indicated that the serum rather than blood has higher diagnostic accuracy. Likewise, meta-regression analysis demonstrated that the specimen, detection method, sample size, and publication year were the main sources of heterogeneity. Sensitivity analysis and Deeks' funnel plot revealed that our results are relatively robust. Conclusions: Our evidence-based analysis results suggested that circRNAs provide higher diagnostic accuracy in the prediction of CVDs. Thus, circRNAs might be potential biomarkers in CVDs.
Subject(s)
Cardiovascular Diseases , RNA, Circular , Biomarkers, Tumor , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/genetics , Humans , Odds Ratio , RNA, Circular/genetics , Sensitivity and SpecificityABSTRACT
Arsenic can cause neurodegenerative diseases of the brain, but the definite mechanism is still unknown. In this study, to discuss the disturbances on brain metabolome and lipidome under subchronic arsenic exposure, we treated mice with the arsenic-containing feed (concentration of total arsenic = 30 mg/kg) prepared in accordance with the proportion of rice arsenicals for 16 weeks and performed metabolomics and lipidomics studies respectively using UHPLC-Triple-TOF-MS/MS and UHPLC-Q Exactive Focus MS/MS on mice brain. In addition, the distributions of arsenical metabolites along the feed-gut-blood-brain chain were analyzed by ICP-MS and HPLC-ICP-MS, and fecal microbial variations were investigated by 16 s sequencing. The data showed that although only a tiny amount of arsenic (DMA=0.101 mg/kg, uAs=0.071 mg/kg) enters the brain through the blood-brain barrier, there were significant changes in brain metabolism, including 118 metabolites and 17 lipids. These different metabolites were involved in 30 distinct pathways, including glycometabolism, and metabolisms of lipid, nucleic acid, and amino acid were previously reported to be correlated with neurodegenerative diseases. Additionally, these different metabolites were significantly correlated with 12 gut bacterial OTUs, among which Lachnospiraceae, Muribaculaceae, Ruminococcaceae, and Erysipelotrichaceae were also previously reported to be related to the distortion of metabolism, indicating that the disturbance of metabolism in the brain may be associated with the disturbance of gut microbes induced by arsenic. Thus, the current study demonstrated that the brain metabolome and lipidome were significantly disturbed under subchronic arsenic exposure, and the disturbances also significantly correlated with some gut microbiome and may be associated with neurodegenerative diseases. Although preliminary, the results shed some light on the pathophysiology of arsenic-caused neurodegenerative diseases.
ABSTRACT
Dysfunctional adipogenesis such as subcutaneous lipoatrophy is closely related to insulin resistance and metabolic disorders. Although the expression or release of the cytokine interleukin-1α (IL-1α) is known to increase in adipose tissue in response to cell death, cell senescence, aging, or solar radiation, the regulatory role of IL-1α in adipogenesis has not been sufficiently investigated. To investigate the problem, we explored the effect of IL-1α on the proliferation and adipogenic differentiation of human adipose-derived mesenchymal stem cells (ADSCs) using cell counting, alamarBlue assay, oil red O staining, Western blot, among others. The results showed that IL-1α evidently inhibited the proliferation and adipogenic differentiation of ADSCs, which might be related with the activated nuclear factor-κB (NF-κB) and extracellular signal-regulated kinase (ERK) 1/2 pathways. Early-stage adipogenic differentiation was more sensitive to IL-1α than late-stage differentiation. After differentiation of ADSCs into mature adipocytes, adding of IL-1α had no obvious influence on the cellular morphology, including lipid droplet accumulation. IL-1α enhanced the expression of proinflammatory cytokines, such as IL-8, IL-6, CCL2 (C-C motif chemokine ligand 2), and IL-1ß, when added into the adipogenic medium of ADSCs. Blocking IL-8 and IL-6 with neutralizing antibodies partially alleviated the inhibitory effect of IL-1α on the proliferation and adipogenic differentiation. The results suggest that IL-1α inhibits adipogenesis through activation of NF-κB and ERK1/2 pathways and subsequent upregulation of proinflammatory cytokines in ADSCs. IL-1α might play an important role in mediating lipoatrophy by regulation of ADSCs.
Subject(s)
Adipogenesis/physiology , Interleukin-1alpha/metabolism , Mesenchymal Stem Cells/cytology , Mitogen-Activated Protein Kinase 3/metabolism , NF-kappa B/metabolism , Adipocytes/cytology , Adipose Tissue/cytology , Adult , Cell Differentiation/physiology , Cell Proliferation/physiology , Cells, Cultured , Humans , MaleABSTRACT
An increasing prevalence of diabetes is known as a main risk for human health in the last future worldwide. There is limited evidence on the potential management of type 2 diabetes mellitus using bioactive peptides from marine organisms, besides from milk and beans. We summarized here recent advances in our understanding of the regulation of glucose metabolism using bioactive peptides from natural proteins, including regulation of insulin-regulated glucose metabolism, such as protection and reparation of pancreatic ß-cells, enhancing glucose-stimulated insulin secretion and influencing the sensitivity of insulin and the signaling pathways, and inhibition of bioactive peptides to dipeptidyl peptidase IV, α-amylase and α-glucosidase activities. The present paper tried to understand the underlying mechanism involved and the structure characteristics of bioactive peptides responsible for its antidiabetic activities to prospect the utilization of rich marine organism proteins.
Subject(s)
Aquatic Organisms/chemistry , Diabetes Mellitus, Type 2/drug therapy , Peptides/pharmacology , Blood Glucose/drug effects , Dipeptidyl Peptidase 4/chemistry , Dipeptidyl Peptidase 4/pharmacology , Glucose/metabolism , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Insulin/metabolism , Peptides/chemistry , alpha-Amylases/chemistry , alpha-Amylases/pharmacology , alpha-Glucosidases/chemistry , alpha-Glucosidases/pharmacologyABSTRACT
Peptides derived from dietary proteins, have been reported to display significant antioxidant activity, which may exert notably beneficial effects in promoting human health and in food processing. Recently, much research has focused on the generation, separation, purification and identification of novel peptides from various protein sources. Some researchers have tried to discover the structural characteristics of antioxidant peptides in order to lessen or avoid the tedious and aimless work involving the ongoing generated peptide preparation schemes. This review aims to summarize the current knowledge on the relationship between the structural features of peptides and their antioxidant activities. The relationship between the structure of the precursor proteins and their abilities to release antioxidant fragments will also be summarized and inferred. The preparation methods and antioxidant capacity evaluation assays of peptides and a prediction scheme of quantitative structure-activity relationship (QSAR) will also be pointed out and discussed.
Subject(s)
Amino Acids/chemistry , Antioxidants/chemistry , Dietary Proteins/metabolism , Peptide Fragments/chemistry , Amino Acid Sequence , Amino Acids/metabolism , Amino Acids/pharmacology , Antioxidants/metabolism , Antioxidants/pharmacology , Biological Products/administration & dosage , Dietary Proteins/administration & dosage , Dietary Proteins/pharmacology , Humans , Hydrophobic and Hydrophilic Interactions , Molecular Sequence Data , Peptide Fragments/metabolism , Peptide Fragments/pharmacology , Proteolysis , Quantitative Structure-Activity Relationship , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/metabolism , Static ElectricityABSTRACT
Mangiferin is a xanthone widely distributed in higher plants showing antioxidative, antiviral, anticancer, antidiabetic, immunomodulatory, hepatoprotective and analgesic effects. In the present study, an ultrasonic-assisted extraction method was developed for the effective extraction of mangiferin from mango leaves. Some parameters such as ethanol concentration, liquid-to-solid ratio, extraction temperature, and extraction time were optimized by single-factor experiment and response surface methodology. The optimal extraction conditions were 44% ethanol, the liquid-to-solid ratio was 38:1, and extraction for 19.2 min at 60 °C under ultrasound irradiation of 200 W. Under optimal conditions, the yield of mangiferin was 58.46 ± 1.27 mg/g. The results obtained are helpful for the full utilization of mango leaves, and also indicated that ultrasonic-assisted extraction is a very useful method for the extraction of mangiferin from plant materials.
Subject(s)
Mangifera/chemistry , Plant Leaves/chemistry , Xanthones/isolation & purification , Ethanol/chemistry , Sound , Temperature , Xanthones/chemistryABSTRACT
AIMS: The study aims to investigate the role and underlying mechanisms of tricetin in regulating hepatic stellate cells (HSCs) activation. MAIN METHODS: We treated human hepatic stellate cells line LX-2 and freshly isolated primary mouse hepatic stellate cells (mHSCs) with tricetin, pharmacological inhibitors and siRNAs, western blot, immunofluorescence, quantitative PCR were used to evaluate the expression of fibrotic markers, autophagy levels and Nrf2 (nuclear factor E2-related factor 2) signaling. KEY FINDINGS: Herein, we demonstrated that tricetin strongly attenuated the proliferation, migration, lipid droplets (LDs) loss and fibrotic markers Col 1a1 (type I α 1 collagen) and α-SMA (α-smooth muscle actin) expression in LX-2 cells. Moreover, tricetin time- and dose-dependently provoked autophagic formation in LX-2 cells. Autophagy inhibition by pharmacological intervention or genetic ATG5 (autophagy related 5) silencing facilitated tricetin-induced downregulation of profibrotic markers in LX-2 cells. Additionally, tricetin treatment reduced reactive oxygen species (ROS) accumulation, promoted Nrf2 signaling in LX-2 cells and pretreatment with ROS scavenger NAC partially reversed tricetin-induced autophagy and enhanced tricetin-mediated HSCs inactivation. Nrf2 silencing partially reversed tricetin-mediated inhibition of α-SMA expression. Finally, utilizing primary mouse hepatic stellate cells (mHSCs), we demonstrated that tricetin also induced autophagy activation, repressed TGF-ß1-induced LDs loss and fibrotic marker expression and pretreatment with CQ further sensitized these effects. SIGNIFICANCE: Our study indicates that tricetin's actions may represent an effective strategy to treat liver fibrosis and help identify novel therapeutic targets, especially in combination with autophagy inhibitors.
Subject(s)
Autophagy , Hepatic Stellate Cells , Liver Cirrhosis , NF-E2-Related Factor 2 , Signal Transduction , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/drug effects , Hepatic Stellate Cells/pathology , Autophagy/drug effects , NF-E2-Related Factor 2/metabolism , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Liver Cirrhosis/drug therapy , Animals , Humans , Signal Transduction/drug effects , Mice , Reactive Oxygen Species/metabolism , Mice, Inbred C57BL , Cell Line , Cell Proliferation/drug effects , MaleABSTRACT
SCOPE: Bile acids play a crucial role in lipid absorption and the regulation of lipid, glucose, and energy homeostasis. Coenzyme Q10 (CoQ10), a lipophilic antioxidant, has been recognized for its positive effects on obesity and related glycolipid metabolic disorders. However, the relationship between CoQ10 and bile acids has not yet been evaluated. METHODS AND RESULTS: This study assesses the impact of CoQ10 treatment on bile acid metabolism in mice on a high-fat diet using Ultra-Performance Liquid Chromatography-tandem Mass Spectrometry. CoQ10 reverses the reduction in serum and colonic total bile acid levels and alters the bile acid profile in mice that are caused by a high-fat diet. Seventeen potential targets of CoQ10 in bile acid metabolism are identified by network pharmacology, with six being central to the mechanism. Molecular docking shows a high binding affinity of CoQ10 to five of these key targets. Further analyses indicate that farnesoid X (FXR) receptor and Takeda G-protein coupled receptor 5 (TGR5) may be crucial targets for CoQ10 to regulate bile acid metabolism and exert beneficial effects. CONCLUSION: This study sheds light on the impact of CoQ10 in bile acids metabolism and offers a new perspective on the application of CoQ10 in metabolic health.
Subject(s)
Bile Acids and Salts , Diet, High-Fat , Dietary Supplements , Mice, Inbred C57BL , Molecular Docking Simulation , Network Pharmacology , Receptors, Cytoplasmic and Nuclear , Ubiquinone , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology , Bile Acids and Salts/metabolism , Animals , Receptors, Cytoplasmic and Nuclear/metabolism , Male , Receptors, G-Protein-Coupled/metabolism , MiceABSTRACT
Mangiferin is the main bioactive component in mango leaves, which possesses anti-inflammatory, antioxidative, antidiabetic, immunomodulatory, and antitumor activities. In the present study, a microwave-assisted extraction method was developed for the extraction of mangiferin from mango leaves. Some parameters such as ethanol concentration, liquid-to-solid ratio, microwave power, and extraction time were optimized by single-factor experiments and response surface methodology. The optimal extraction conditions were 45% ethanol, liquid-to-solid ratio of 30:1 (mL/g), and extraction time of 123 s under microwave irradiation of 474 W. Under optimal conditions, the yield of mangiferin was 36.10 ± 0.72 mg/g, significantly higher than that of conventional extraction. The results obtained are beneficial for the full utilization of mango leaves and also indicate that microwave-assisted extraction is a very useful method for extracting mangiferin from plant materials.
Subject(s)
Chemical Fractionation/methods , Mangifera/chemistry , Plant Extracts/isolation & purification , Plant Leaves/chemistry , Xanthones/isolation & purification , Chemical Fractionation/instrumentation , MicrowavesABSTRACT
Astaxanthin is a novel carotenoid nutraceutical occurring in many crustaceans and red yeasts. It has exhibited various biological activities including prevention or amelioration of cardiovascular disease, gastric ulcer, hypertension, and diabetic nephropathy. In this study, ultrasound-assisted extraction was developed for the effective extraction of astaxanthin from Haematococcus pluvialis. Some parameters such as extraction solvent, liquid-to-solid ratio, extraction temperature, and extraction time were optimized by single-factor experiment and response surface methodology. The optimal extraction conditions were 48.0% ethanol in ethyl acetate, the liquid-to-solid ratio was 20:1 (mL/g), and extraction for 16.0 min at 41.1 °C under ultrasound irradiation of 200 W. Under optimal conditions, the yield of astaxanthin was 27.58 ± 0.40 mg/g. The results obtained are beneficial for the full utilization of Haematococcus pluvialis, which also indicated that ultrasound-assisted extraction is a very useful method for extracting astaxanthin from marine life.
Subject(s)
Chlorophyta/chemistry , Ultrasonography/methods , Solvents/chemistry , Temperature , Time Factors , Xanthophylls/isolation & purificationABSTRACT
CONTEXT: The relationship between food restriction (FR) and liver enzyme levels, such as alanine transferase (ALT), aspartate transferase (AST), and γ-glutamyl transferase (GGT), has not yet been confirmed. OBJECTIVE: A meta-analysis of research articles was conducted to investigate the association of FR and liver enzyme levels. DATA SOURCES: The PubMed, Web of Science, Embase, and Cochrane Library databases were screened for articles published up to April 30, 2022. DATA EXTRACTION: Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement methodology was used to search for research articles. Publication bias was detected using Begg's test. Finally, 17 trials involving 1982 participants and that reported mean value, mean difference, and standard deviation were identified. DATA ANALYSIS: Data were described as the weighted mean difference of body mass index, body weight, and standardized mean difference (SMD) of ALT, AST, and GGT. A reduction in ALT level was observed after a FR intervention (total SMD, -0.36, 95% confidence interval [CI], -0.68 to -0.05). GGT levels also were decreased in 4 studies (total SMD, -0.23; 95%CI, -0.33 to -0.14). According to subgroup analysis, serum AST levels decreased in the medium-term (between 5 wk and 6 mo) group (subtotal SMD, -0.48; 95%CI, -0.69 to -0.28). CONCLUSION: Existing evidence suggests that dietary restriction improves adult liver enzyme levels. The long-term maintenance of healthy liver enzyme levels, particularly in real-world applications, necessitates additional consideration.
Subject(s)
Food , Liver , gamma-Glutamyltransferase , Adult , Humans , Body Mass Index , Body WeightABSTRACT
Cyanidin-3-glucoside (C3G) is a member of the anthocyanin family which belongs to the flavonoid class and possesses antiatherogenic properties. Many studies have demonstrated the protective effects of C3G on vascular endothelial cells and monocytes, however, the precise effects on vascular smooth muscle cells (VSMCs) have been less thoroughly studied. Hence, we investigated the role of C3G in TNF-α-induced VSMCs proliferation and explored the possible mechanisms. TNF-α stimulated VSMCs proliferation, and pretreatment with C3G inhibited the proliferation in dose- and time-dependent manners. Then, we found that C3G attenuated TNF-α-induced ROS over generation by Dihydroethidium staining. The combination of 50 µM C3G and 100 µM apocynin significantly reduced ROS generation. Moreover, C3G pretreatment significantly suppressed the expression of Nox activator 1, a subunit of NADPH oxidase in mouse VSMCs. C3G also inhibited TNF-α-induced signal transducer and activator of transcription (STAT3) phosphorylation, and the inhibitory effect was more prominent in C3G and apocynin co-pretreated cells than that pretreated with C3G or apocynin alone. Administration of the ROS scavenger catalase (2,000 U/ml) remarkably inhibited TNF-α-induced cell proliferation and STAT3 activation. These data suggest that C3G exerts its antiproliferative effect on TNF-α-induced VSMCs proliferation through inhibiting STAT3 activation by attenuating NoxA1-derived ROS over production.
Subject(s)
Anthocyanins/pharmacology , Glucosides/pharmacology , Muscle, Smooth, Vascular/metabolism , Proteins/metabolism , STAT3 Transcription Factor/metabolism , Tumor Necrosis Factor-alpha/metabolism , Acetophenones/pharmacology , Adaptor Proteins, Signal Transducing , Animals , Catalase/pharmacology , Cell Proliferation/drug effects , Cells, Cultured , Mice , Mice, Inbred C57BL , Muscle, Smooth, Vascular/drug effects , Phosphorylation , Reactive Oxygen Species/metabolism , Signal Transduction/drug effectsABSTRACT
Mulberry is one of the most widely used traditional Chinese medicines. Anthocyanins are the main bioactive components of mulberry, and possess important biological activities, such as antimicrobial, anti-inflammatory and antioxidant activities. This study investigated the ultrasound-assisted extraction (UAE) of anthocyanins from mulberry by using response surface methodology (RSM). The extraction conditions associated with anthocyanin yield, including extraction solvent, liquid-to-solid rate, temperature and extraction time, are discussed. The optimal conditions obtained by RSM for UAE from mulberry include 63.8% methanol contains 1% (v/v) trifluoroacetic acid (TFA), 43.2 °C temperature, 23.8 (v/w) liquid-to-solid ratio, and 40 min time for the maximum yield (64.70 ± 0.45 mg/g). The results indicated that the UAE can be an effective method for the extraction of some active components from plant materials.
Subject(s)
Anthocyanins/isolation & purification , Morus/chemistry , Ultrasonography/methods , Anthocyanins/chemistry , Chromatography, High Pressure Liquid , Plant Extracts/chemistryABSTRACT
BACKGROUND: It is reported that circular RNAs (circRNAs) play a key role in atherosclerosis (AS). Foam cell formation, which is the main feature of AS, can be significantly inhibited by cholesterol efflux. METHODS: We established a model of astaxanthin (AST) promoting cholesterol efflux from macrophages through oil red O staining, real-time quantitative PCR (qRT-PCR), and western blot and used RNA sequencing to detect the expression of circRNAs in AST-treated and untreated THP-1 cells. Finally, siRNA transfection screened out circRNAs that were significantly differentially expressed. The data analysis was performed by Student's t test and P < 0.05 was considered statistically significant. RESULTS: In the model of AST promoting cholesterol efflux from THP-1 cells, there were a total of 7276 circRNAs differentially expressed, among which the top 25 upregulated and the top 25 downregulated circRNAs were selected based on the log2 (fold change). GO analysis showed that differential expression of circRNAs in biological process (2066/3098; 66.69%), molecular function (543/3098; 17.53%), and cellular component (489/3098; 15.78%). Based on KEGG analysis, RNA transport was the most enriched pathway. Finally, we obtained 3 significantly upregulated circRNAs by siRNA transfection and qRT-PCR. CONCLUSIONS: The 3 differentially expressed circRNAs may play an important role in the process of AST promoting cholesterol efflux and may be used as biomarkers to prevent AS.
ABSTRACT
Background: This meta-analysis aimed to evaluate the diagnostic accuracy of extracellular vesicles (EV) miRNAs for non-small cell lung cancer (NSCLC).Methods: All eligible studies were searched in an online database. Stata 15.0, Meta-disc 14.0 and Review Manager 5.2 software packages were used to perform all statistical analysis.Results: The analysis included 16 articles and 70 studies. Pooled sensitivity (SEN) and specificity (SPE), positive predictive value and negative predictive value were 0.77 (95% CI: 0.72-0.80), 0.83 (95% CI: 0.78-0.86), 0.88 (95% CI: 0.86-0.90) and 0.63 (95% CI: 0.58-0.68), respectively. The overall diagnostic odds ratio (DOR) was 16 (95% CI: 11-21) and the area under the curve (AUC) was 0.86 (95% CI: 0.83-0.89). 3 EV miRNAs could identify metastatic NSCLC from healthy, and 10 distinguish early-stage NSCLC. The respective targets of EV miR-21, miR-210, and miR-1290 could activate PI3K/AKT-related pathway.Conclusion: EV miRNAs had high diagnostic accuracy (AUC = 0.86) for NSCLC, especially metastatic NSCLC (AUC = 0.90), and early-stage NSCLC (AUC = 0.88). Besides, multitudinous EV miRNAs combined showed higher diagnostic value than alone. EV miR-21, miR-210, and miR-1290 might be associated with PI3K/AKT-related pathway and the valuable diagnostic biomarkers for NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Extracellular Vesicles , Lung Neoplasms , MicroRNAs , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Extracellular Vesicles/genetics , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/pathology , MicroRNAs/genetics , Phosphatidylinositol 3-KinasesABSTRACT
BACKGROUND: Recently, many studies have demonstrated that long non-coding RNAs (lncRNAs) are abnormally expressed in hepatocellular carcinoma (HCC) and may serve as a potential molecular biomarker to evaluate the prognosis of hepatocellular carcinoma. Therefore, we accomplished a meta-analysis built on current studies to assess the prognostic value of lncRNAs in hepatocellular carcinoma. METHODS: The PubMed database was carefully searched to collect all eligible studies until February 20, 2019. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of the overall survival, relapse-free survival, and progression-free survival were calculated to evaluate the prognostic significance of lncRNAs expression in hepatocellular carcinoma using Stata12.0 software. Heterogeneity, sensitivity analysis, and publication bias were also evaluated. RESULTS: The results showed that the expression level of lncRNAs was significantly correlated with clinical outcomes. Abnormally expressed lncRNAs predicted poor overall survival (HR=2.19, 95% CI: 1.99-2.42, P<0.001; I2=44.7%, P=0.005), relapse-free survival (HR=2.68, 95% CI: 1.74-4.14, P<0.001; I2=0.0%, P=0.763) and progression-free survival of hepatocellular carcinoma patients (HR=2.44, 95% CI: 1.53-3.89, P<0.001; I2=0.0%, P=0.336). Statistical significance was also noted in subgroup meta-analyses that were stratified by follow-up time, cutoff value, and quality score. Moreover, the pooled results indicated that lncRNAs expression was significantly associated with tumor size (HR=1.48, 95% CI: 1.24-1.79), tumor number (HR=1.34, 95% CI: 1.08-1.66), and tumor node metastasis stage (HR=2.10, 95% CI: 1.48-2.99), but not liver cirrhosis and tumor differentiation (P>0.05). CONCLUSIONS: This meta-analysis indicates that lncRNAs are strongly associated with prognosis in hepatocellular carcinoma and may serve as a promising indicator for prognostic evaluation of patients with hepatocellular carcinoma. But larger clinical studies are needed to verify its feasibility.
Subject(s)
Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , RNA, Long Noncoding/genetics , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Prognosis , Survival AnalysisABSTRACT
LINGO-1(LRR and Ig domain-containing NOGO receptor interacting protein 1) is a viable target for spinal cord injury (SCI) repair due to its potent negative regulation in neuron survival and axonal regeneration. Although promising, the intracellular mechanism underlying LINGO-1 regulation is unclear. Here, we identified miR-615 as a potential microRNA (miRNA) that directly targets LINGO-1 by binding its 3'-untranslated region (3'-UTR) and caused the translation inhibition of LINGO-1. MiR-615 negatively regulated LINGO-1 during neural stem cell (NSC) differentiation and facilitated its neuronal differentiation in vitro. Interestingly, compared to the control, neurons differentiated from miR-615-treated NSCs were immature with short processes. Further results showed LINGO-1/epidermal growth factor receptor (EGFR) signaling may be involved in this process, as blockade of EGFR using specific antagonist resulted in mature neurons with long processes. Furthermore, intrathecal administration of miR-615 agomir in SCI rats effectively knocked down LINGO-1, increased neuronal survival, enhanced axonal extension and myelination, and improved recovery of hindlimbs motor functions. This work thus uncovers miR-615 as an effective miRNA that regulates LINGO-1 in NSC and SCI animals, and suggests miR-615 as a potential therapeutic target for traumatic central nervous system (CNS) injury.
Subject(s)
Cell Differentiation/physiology , Membrane Proteins/metabolism , MicroRNAs/metabolism , Nerve Tissue Proteins/metabolism , Neural Stem Cells/metabolism , Spinal Cord Injuries/metabolism , Animals , Cell Proliferation/physiology , Neurons/metabolism , Rats , Signal Transduction/physiologyABSTRACT
BACKGROUND: The relationship between vitamin D level and NAFLD has not been investigated in children and adolescents. We performed a meta-analysis of published observational studies to assess this association between vitamin D levels (measured as serum 25-hydroxy vitamin D [25(OH)D]) and NAFLD in this age group. METHODS: Relevant studies conducted before May 20, 2018, were identified from the following electronic databases: PubMed, the Cochrane Library, Embase, and the Chinese CNKI databases. The quality of the included studies was evaluated using the Newcastle Ottawa Scale, and associations between vitamin D levels and NAFLD were estimated using standardised mean differences (SMD) and 95% confidence interval (CI). Subgroup and sensitivity analysis were used to identify sources of heterogeneity, and publication bias was evaluated using funnel plots. RESULTS: Eight articles were included in this meta-analysis. A significant difference was observed between low 25(OH)D levels and NAFLD in children and adolescents (SMD = -0.59, 95%CI = -0.98, -0.20, P <â 0.01). Subgroup analysis revealed no differences in the study type, geographic location, BMI, and age subgroups. CONCLUSIONS: Low vitamin D levels were associated with NAFLD in children and adolescents.
Subject(s)
Non-alcoholic Fatty Liver Disease/blood , Vitamin D Deficiency/blood , Vitamin D/blood , Adolescent , Child , Humans , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/pathology , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/pathologyABSTRACT
The aim of the present study was to investigate the role of microRNAs (miRNAs/miRs) in the antifibrotic effect of astaxanthin (AST), using the human hepatic stellate cell (HSC) line LX2 as the research model. LX2 cells were treated with various concentrations of AST (10, 20 and 40 µM) for 24 or 48 h. miR29b was selected based on existing literature, and its targeting gene B cell lymphoma (Bcl)2 was predicted by TargetScan and miRanda databases for further analysis. Interactions between miR29b and Bcl2 in the AST treated LX2 cells were evaluated using reverse transcriptionquantitative polymerase chain reaction (RTqPCR) and western blot analysis. MTT analysis was used to analyze cell viability. Overexpression of miR29b decreased the expression of Bcl2 in ASTtreated LX2 cells, and silencing of it had the opposite effect. Additionally, Annexin Vfluorescein isothiocyanate/propidium iodide double staining and flow cytometry were used to evaluate the cell apoptosis, and overexpression of miR29b increased cell apoptosis rates in ASTtreated LX2 cells; however, silencing of it had the opposite effect. RTqPCR and western blotting demonstrated that AST induced LX2 cells apoptosis which may be by regulating miR29b, as indicated by inhibited Bcl2 expression levels and elevated Bax and Caspase3 expression levels. These results highlight an important role of miR29b in the AST modulating LX2 cells proliferation and apoptosis and implicate a potential mechanism of miR29b and AST preventing liver fibrosis.