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BACKGROUND: A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation. METHODS: PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021. Data extraction and analysis were performed for the populations, distribution, predictors, algorithms, etc. The risk of bias was evaluated with the prediction risk of bias assessment tool (PROBAST). Subsequently, we designed IVS for model replicability evaluation with five steps in five items, including transparency of algorithms, performance of models, feasibility of reproduction, risk of reproduction, and clinical implication, respectively. The review is registered in PROSPERO (No. CRD42021271789). RESULTS: In 20,887 screened references, 79 articles (82.5% in 2017-2021) were included, which contained 114 datasets (67 in Europe and North America, but 0 in Africa). We identified 486 AI-Ms, of which the majority were in development (n = 380), but none of them had undergone independent external validation. A total of 66 idiographic algorithms were found; however, 36.4% were used only once and only 39.4% over three times. A large number of different predictors (range 5-52,000, median 21) and large-span sample size (range 80-3,660,000, median 4466) were observed. All models were at high risk of bias according to PROBAST, primarily due to the incorrect use of statistical methods. IVS analysis confirmed only 10 models as "recommended"; however, 281 and 187 were "not recommended" and "warning," respectively. CONCLUSION: AI has led the digital revolution in the field of CVD prediction, but is still in the early stage of development as the defects of research design, report, and evaluation systems. The IVS we developed may contribute to independent external validation and the development of this field.
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Inteligência Artificial , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/diagnóstico , Medição de Risco/métodos , Programas de Rastreamento/métodos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The protocol for delayed-interval delivery of the second twin in twin pregnancies has not been standardized. Cervical cerclage is often performed, but its use is debated. To conduct a scoping review on cervical cerclage for prolonging the intertwin delivery interval and improving second twin survival and maternal outcomes after preterm delivery or spontaneous abortion of the first twin in twin pregnancies. METHODS: Seven Chinese and English language databases were searched from inception to March 1, 2023, including PubMed, The Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP Chinese Science Journal Database, and Sinomed. Relevant observational studies that assessed the effectiveness of the use of cervical cerclage in delayed-interval delivery of twins were screened and selected, and raw data were extracted, and descriptive statistics and chi-square analysis were performed. RESULTS: A total of 102 articles were retrieved. After screening and exclusion of duplicate and irrelevant articles, 22 articles meeting the inclusion criteria were obtained. Studies in which cerclage was performed reported longer intertwin delivery intervals than those that did not perform cerclage, and the difference was statistically significant. The cerclage group also tended to have lower rates of chorioamnionitis and maternal complications, but the difference between the two groups was not statistically significant. CONCLUSION: After excluding patients with contraindications, emergency cervical cerclage can be considered in cases of spontaneous abortion of the first twin in twin pregnancies to prolong the gestation and improve the prognosis of the remaining fetus until it becomes viable and increases its birth weight.
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Cerclagem Cervical , Parto Obstétrico , Gravidez de Gêmeos , Feminino , Humanos , Gravidez , Aborto Espontâneo , Cerclagem Cervical/métodos , Parto Obstétrico/métodos , Resultado da Gravidez , Nascimento Prematuro/prevenção & controle , Fatores de TempoRESUMO
BACKGROUND: Multiple negative health outcomes were linked to residential proximity to major roadways. Nevertheless, there is limited knowledge regarding the association between residential proximity to major roadways and chronic multimorbidity. METHODS: We used data from the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey, which included 12,214 individuals aged ≥ 60. We derived the residential proximity to major roadways from self-reported data, defining chronic multimorbidity as the presence of two or more concurrent chronic diseases. A binary logistic regression model was utilized to investigate the association between residential proximity to major roadways and chronic multimorbidity. The model accounted for some demographic features, socioeconomic conditions, social participation, and health conditions. Subsequently, we conducted subgroup analyses to examine potential interaction effects. RESULTS: Residential proximity to major roadways was associated with chronic multimorbidity, even after adjusting for confounding factors. Compared with those living > 300 m from major roadways, the OR for those living 201-300 m, 101-200 m, 50-100 m, and < 50 m were increased. When subgroup analyses were conducted using a cutoff point of 200 m, the risk of chronic multimorbidity associated with residential proximity to major roadways was stronger in participants with education levels > 6 years (P = 0.017). CONCLUSION: Our findings provide important implications for improving residential area siting, transportation policies, and environmental regulations to reduce the risk of chronic multimorbidity caused by traffic-related exposure.
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Multimorbidade , Emissões de Veículos , Humanos , Idoso , Emissões de Veículos/análise , Estudos Transversais , Modelos Logísticos , China/epidemiologiaRESUMO
BACKGROUND AND AIMS: Gout is a chronic self-limiting inflammatory arthritis. An increase in metallothionein-1 (MT-1) has been reported in rheumatoid arthritis and osteoarthritis, and it attenuates inflammation and the pathology of diseases. This study aims to detect MT-1 levels in patients with gout and to explore its correlation with disease activity, clinical indexes, and inflammatory cytokines. METHODS: The expression of MT-1 messenger RNAs (mRNAs) and protein levels in patients with gout were measured using real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Correlations between MT-1 and clinical indexes or inflammatory mediators were analyzed using Spearman's correlation test. RESULTS: Compared with healthy controls (HCs, n = 43), patients with active gout (n = 27) showed higher levels of MT-1 mRNA in peripheral blood mononuclear cells and protein in serum, particularly those with tophi. No significant difference in serum MT-1 levels was observed among patients with inactive gout, HCs, and patients with hyperuricemia without gout. Furthermore, no significant difference was observed between patients with gout with kidney damage and HCs. In addition, serum interleukin (IL)-1ß, IL-6, and IL-8 levels were significantly increased in patients with active gout, particularly in those with tophi. The serum MT-1 level was positively correlated with C-reactive protein, as well as with IL-1ß, IL-6, and IL-18. CONCLUSION: The higher levels of MT-1 were found in patients with gout, which were correlated with disease activity and gout related pro-inflammatory cytokines. Indicating MT-1 may serve as a new marker for predicting disease activity.Abbreviations: IL-1ß: Interleukin 1ß; MT-1: Metallothionein-1; CRP: C-Reactive Protein; ROS: Reactive Oxygen Species; IL-10: Interleukin 10; TGF-ß: Transforming Growth Factor Beta.
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Gota , Interleucina-6 , Humanos , Interleucina-6/genética , Leucócitos Mononucleares/metabolismo , Proteína C-Reativa/metabolismo , Metalotioneína/genética , Metalotioneína/metabolismo , Gota/genética , Citocinas/metabolismoRESUMO
Non-small cell lung cancer (NSCLC) is a common lung disorder. In this study, we applied bioinformatics methods to analyze and investigate the role of the NFIX gene in NSCLC. Hsa_circ_0049657 is derived from the NFIX gene, this research aimed to verify the potential role of hsa_circ_0049657 in the development of NSCLC. The results suggested that NFIX was downregulated in most cancers. In addition, the NFIX expression in lung adenocarcinoma (LUAD) was associated with the clinicopathological stage. In LUAD, NFIX expression was associated with the degree of infiltration of most immune cells. The expression levels of hsa_circ_0049657 were significantly lower in cancerous tissues than in paracancerous tissues. Moreover, the results showed that hsa_circ_0049657 expression was downregulated in NSCLC cells. After overexpression of hsa_circ_0049657, the proliferation and migration ability of NSCLC cells were significantly inhibited and the level of apoptosis was increased. We could suppress the proliferation and invasion abilities and promote apoptosis of NSCLC cells by up-regulating hsa_circ_0049657, which might be a potential biomarker for NSCLC.
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Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , RNA Circular/genética , Neoplasias Pulmonares/genética , BiomarcadoresRESUMO
The dynamic behavior of droplets impacting on textured surfaces has an important influence on many engineering applications, such as anti-icing and self-cleaning. However, the mechanism and law of the effect of textured surfaces on the impact behavior of nanodroplets has not been fully revealed yet. In this paper, the molecular dynamics (MD) method is used to model the dynamic behavior of nanodroplets after impacting the solid surface with a striped texture. The influences of texture gap and texture angle on the real contact area, spreading factor, contact time, and bounce velocity of the droplet after impact are also quantitatively analyzed. It is shown that the striped texture produces significant anisotropy in the spreading and contraction behavior of nanodroplets after impact, and the anisotropy is more pronounced on the ridged texture surface than on the grooved texture surface. In addition, we find that the texture gap has little effect on the dynamic behavior of nanodroplets impacting the textured surface. However, as the bottom angle of the texture increases, the real contact area and bounce velocity of the nanodroplet increase significantly, while the contact time and spreading factor decrease. This work further elucidates the characteristics and mechanisms of nanodroplets impacting on stripe-textured surfaces and provides a theoretical basis for the design of nanostructured surfaces in relevant applications.
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Background: LncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) was competitive endogenous RNA (ceRNA) involved in various molecular processes for metastasis development in lung cancer. Single nucleotide polymorphisms (SNPs) in MALAT1 gene might be predictive markers for lung cancer. In our study, we selected rs619586 and rs3200401 in MALAT1 gene to explore their effects on lung cancer susceptibility. Methods: The case-control study included 444 lung cancer cases and 460 healthy controls. Genotyping was performed by Taqman allelic discrimination method. Logistic regression, Student t-test, and Chi-square test (χ2 ) were used to analyze the data. Results: The findings of the study showed that rs3200401 was significantly associated with the risk of non-small cell lung cancer (NSCLC) and lung squamous cell carcinoma (LUSC). Compared with homozygous CC genotype, CT heterozygous genotype decreased risk of NSCLC (Pa = 0.034) and LUSC (Pa = 0.025). In addition, no statistical association was detected between rs619586 and lung cancer susceptibility. The interactions between genes and cigarette smoking were discovered via crossover analysis. However, there were no remarkable gene-environment interactions in additive and multiplicative model. Conclusion: Rs3200401 in lncRNA MALAT1 was associated with the susceptibility of non-small-cell lung cancer and lung squamous cell carcinoma. The gene-environmental (cigarette smoking) interactions were not notable.
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Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , RNA Longo não Codificante , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , China/epidemiologia , Fumar Cigarros/efeitos adversos , Fumar Cigarros/genética , Interação Gene-Ambiente , Predisposição Genética para Doença/genética , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único/genética , RNA Longo não Codificante/genéticaRESUMO
PURPOSE: Thyroid cancer (TC) is the most common malignancy of the endocrine system and its incidence is gradually rising. Research has demonstrated a close link between autophagy and thyroid cancer. We constructed a prognostic model of autophagy-related long non-coding RNA (lncRNA) in thyroid cancer and explored its prognostic value. METHODS: The data used in this study were all obtained from The Cancer Genome Atlas (TCGA) database and the Human Autophagy Database (HADb). We construct a co-expression network by autophagy-related genes and lncRNA to obtain autophagy-related lncRNAs. After univariate Cox regression analysis and multivariate Cox regression analysis, autophagy-related lncRNAs significantly associated with prognosis were identified. Based on the risk score of lncRNA, thyroid cancer patients are divided into high-risk group and low-risk group. RESULTS: A total of 14,142 lncRNAs and 212 autophagy-related genes (ATGs) were obtained from the TCGA database and the HADb, respectively. We performed lncRNA-ATGs correlation analysis and finally obtained 1,166 autophagy-associated lncRNAs. Subsequently, we conducted univariate Cox regression analysis and multivariate Cox regression analysis, nine autophagy-related lncRNAs (AC092279.1, AC096677.1, DOCK9-DT, LINC02454, AL136366.1, AC008063.1, AC004918.3, LINC02471 and AL162231.2) significantly associated with prognosis were identified. Based on these autophagy-related lncRNAs, a risk model was constructed. The area under the curve (AUC) of the risk score was 0.905, proving that the accuracy of risk signature was superior. In addition, multiple regression analysis showed that risk score was a significant independent prognostic risk factor for thyroid cancer. CONCLUSION: In this study, nine autophagy-related lncRNAs in thyroid cancer were established to predict the prognosis of thyroid cancer patients.
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RNA Longo não Codificante , Neoplasias da Glândula Tireoide , Autofagia/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , RNA Longo não Codificante/genética , Neoplasias da Glândula Tireoide/genéticaRESUMO
BACKGROUND: Systemic lupus erythematosus (SLE) is a representative systemic autoimmune disease. LncRNA H19 has been identified to participate in various biological processes in human diseases. However, the role of H19 in SLE remains unclear. METHODS: In this study, we first examined H19 expression in SLE patients by RT-qPCR and found that H19 expression was significantly upregulated in the serum and bone marrow-derived mesenchymal stem cells (BMMSCs) of SLE patients and positively associated with SLE disease activity index. We then performed gain-of-function and loss-of-function using mimic-H19 (H19-OE) and inhibitor-H19 (H19-KD) to examine the effects of H19 on BMMSC differentiation, proliferation, migration, and apoptosis using flow cytometry, DAPI staining, and migration and apoptosis assays. RESULTS: The results showed that H19 inhibited proliferation and migration but promoted apoptosis of BMMSCs, interfered with BMMSCs-mediated Treg cell proliferation and differentiation, and regulated BMMSCs-mediated Tfh/Treg cell balance. Dual-luciferase reporter assay confirmed the in silico prediction of interaction between H19 and IL-2. Furthermore, RT-qPCR showed that H19 directly inhibited IL-2 transcription in BMMSCs. ELISA showed that both active and total IL-2 protein levels were significantly lower in SLE BMMSCs. More importantly, we found that IL-2 significantly enhanced H19-OE-induced Treg cell differentiation and migration of BMMSCs, and these effects were reversed by anti-IL-2 antibody. CONCLUSION: Overall, our study indicates that LncRNA H19 induces immune dysregulation of BMMSCs, at least partly, by inhibiting IL-2 production and might be a novel therapeutic target for SLE.
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Regulação da Expressão Gênica , Imunomodulação/genética , Interleucina-2/biossíntese , Células-Tronco Mesenquimais/metabolismo , RNA Longo não Codificante/genética , Apoptose/genética , Biomarcadores , Estudos de Casos e Controles , Diferenciação Celular/genética , Movimento Celular , Células Cultivadas , Técnicas de Cocultura , Suscetibilidade a Doenças , Humanos , Interleucina-2/genética , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismoRESUMO
OBJECTIVE: The long non-coding RNA plays an important role in inflammation and autoimmune diseases. The aim of this study is to screen and identify abnormally expressed lncRNAs in peripheral blood neutrophils of SLE patients as novel biomarkers and to explore the relationship between lncRNAs levels and clinical features, disease activity and organ damage. METHODS: RNA-seq technology was used to screen differentially expressed lncRNAs in neutrophils from SLE patients and healthy donors. Based on the results of screening, candidate lncRNA levels in neutrophils of 88 SLE patients, 35 other connective disease controls, and 78 healthy controls were qualified by real-time quantitative polymerase chain reaction. RESULTS: LncRNA expression profiling revealed 360 up-regulated lncRNAs and 224 down-regulated lncRNAs in neutrophils of SLE patients when compared with healthy controls. qPCR assay validated that the expression of Lnc-FOSB-1:1 was significantly decreased in neutrophils of SLE patients when compared with other CTD patients or healthy controls. It correlated negatively with SLE Disease Activity Index 2000 (SLEDAI-2K) score (r = -0.541, P < 0.001) and IFN scores (r = -0.337, P = 0.001). More importantly, decreased Lnc-FOSB-1:1 expression was associated with lupus nephritis. Lower baseline Lnc-FOSB-1:1 level was associated with higher risk of future renal involvement (within an average of 2.6 years) in patients without renal disease at baseline (P = 0.019). CONCLUSION: LncRNA expression profile in neutrophils of SLE patients revealed differentially expressed lncRNAs. Validation study on Lnc-FOSB-1:1 suggest that it is a potential biomarker for prediction of near future renal involvement.
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Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , Neutrófilos/metabolismo , RNA Longo não Codificante/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores/metabolismo , Estudos de Casos e Controles , Regulação para Baixo , Perfilação da Expressão Gênica , Humanos , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/metabolismo , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima , Adulto JovemRESUMO
BACKGROUND: Some studies on the relationship between LINC00673 polymorphism and cancer susceptibility have been inconsistent. To perform a more comprehensively quantitative assessment of LINC00673 rs11655237 and risk of overall cancer, we operated this meta-analysis for the first time. METHODS: A comprehensive search was conducted to obtain relevant literature up to November 20, 2019. Pooled odds ratios and 95% confidence intervals were utilized to assess rs11655237 and cancer susceptibility under five different genetic models. RESULTS: Eventually, 11 case-control studies from 9 articles were included. We found that LINC00673 rs11655237 polymorphism increased the susceptibility to overall cancer under all genetic models in the overall population. By dividing ethnicity and cancer type into subgroups, we also obtained similar positive results in subgroups of Chinese population, pancreatic cancer, cervical cancer, neuroblastoma, hepatoblastoma and gastric cancer. CONCLUSION: Overall, this meta-analysis has demonstrated for the first time that LINC00673 rs11655237 could increase susceptibility to cancer.
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Predisposição Genética para Doença , Neoplasias/genética , Polimorfismo Genético , RNA Longo não Codificante/genética , Estudos de Casos e Controles , HumanosRESUMO
We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (pâ¯=â¯0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (ORâ¯=â¯1.31, 95% CI: 1.03, 1.66, pâ¯=â¯0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.
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Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , Tuberculose Pulmonar/genética , Adenocarcinoma de Pulmão/epidemiologia , Povo Asiático , Feminino , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Pulmonares/epidemiologia , Análise da Randomização Mendeliana , não Fumantes/estatística & dados numéricos , Tuberculose Pulmonar/epidemiologiaRESUMO
BACKGROUND: Long non-coding RNAs became the hot spots in the carcinogenesis of various tumors. This case-control study evaluated the association between the rs2151280 in lncRNA CDKN2B-AS1 and lung cancer risk. METHODS: This study included 507 lung cancer patients and 542 healthy individuals. Odds ratios and their 95% confidence intervals were calculated by unconditional logistic regression analysis to evaluate the association between the rs2151280 and lung cancer risk. RESULTS: Compared with individuals carrying TT genotype, individuals carrying CC genotype of rs2151280 had a decreased risk of lung cancer (OR = 0.640, 95%CI = 0.421-0.972, P = 0.036). In the recessive model, rs2151280 CC genotype was observed to reduce the risk of lung cancer (OR = 0.684). C allele was associated with non-small cell lung cancer risk (OR = 0.674). The rs2151280 was significantly associated with lung adenocarcinoma risk (CCvsTT: OR = 0.567, 95%CI = 0.333-0.965, P = 0.037; CCvsTC+TT: OR = 0.543, 95%CI 0.330-0.893, P = 0.016, respectively). However, there was no significant association between rs2151280 and lung squamous cell carcinoma risk in five models. The quantitative analysis suggested that there were no significant interactions of rs2151280 with smoking exposure to lung cancer susceptibility. CONCLUSIONS: This hospital-based case-control study suggested that CDKN2B-AS1 rs2151280 T>C was associated with the risk of lung cancer.
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Povo Asiático/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único/genética , RNA Longo não Codificante/genética , Fumar/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: Most studies revealed that microRNAs could play important roles in the development of various types of cancers. However, the findings remain inconsistent and controversial. To get more accurate results about the association of miR-26a-1 rs7372209 and miR-423 rs6505162 polymorphisms with risk of cancer, we conduct this meta-analysis. MATERIALS AND METHODS: We have searched relevant articles from the PubMed, Web of Science, Wanfang, and Chinese National Knowledge Infrastructure databases up to May 3, 2019. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed to assess the relationship between these two genetic polymorphisms and susceptibility to cancer. All statistical analyses were performed with Stata 12.0 software. RESULTS: Thirty-five articles were eligible in this meta-analysis, including 17,746 cases and 21,808 controls. Our results suggested that the miR-26a-1 rs7372209 polymorphism was associated with the susceptibility to overall cancer significantly in homozygote comparison and recessive model (TT versus CC: OR = 1.167, 95% CI: 1.025-1.329, P = 0.020; TT versus CT + CC: OR = 1.162, 95% CI: 1.025-1.318, P = 0.019). For miR-423 rs6505162, this study showed that the relationship between it and overall cancer susceptibility was statistically significant among five genetic models (CA versus CC: OR = 0.884, 95% CI: 0.806-0.969, P = 0.009; AA + CA versus CC: OR = 0.870, 95% CI: 0.789-0.959, P = 0.005; AA versus CA + CC: OR = 0.904, 95% CI: 0.827-0.988, P = 0.026; A versus C: OR = 0.899, 95% CI: 0.834-0.970, P = 0.006) rather than homozygote model. CONCLUSIONS: Rs7372209 in miR-26a-1 and rs6505162 in miR-423 are associated with overall cancer susceptibility.
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Predisposição Genética para Doença , MicroRNAs/genética , Modelos Genéticos , Neoplasias/genética , Humanos , Razão de ChancesRESUMO
PURPOSE OF REVIEW: MicroRNAs (miRNAs) play essential roles in immune abnormalities and organ damage of systemic lupus erythematosus (SLE). Current findings have indicated potential clinical applications of miRNAs for combating SLE. Here, we review recent evidence which support the notions that miRNAs can be novel biomarkers and therapeutic agents for SLE. RECENT FINDINGS: Following years of the studies of the expression patterns of miRNAs in both peripheral blood cells and body fluids, such as plasma and urine, several miRNAs or miRNA combinations have been associated with disease activity and specific organ damage. In depth analysis reveals complex and multiple roles of certain miRNAs in the pathogenesis of SLE. Manipulating miRNA expression shows in vivo therapeutic effects in lupus mouse models. MiRNAs contribute to the immune disorders and organ damage in SLE. MiRNA based biomarkers and therapies have the potential to be viable options for the treatment of SLE.
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Lúpus Eritematoso Sistêmico , MicroRNAs , Animais , Biomarcadores , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/terapia , Camundongos , MicroRNAs/genéticaRESUMO
Many microRNAs (miRNAs) play vital roles in the tumorigenesis and development of cancers. In this study, we aimed to identify the differentially expressed miRNAs and their specific mechanisms in non-small-cell lung cancer (NSCLC). Based on data from the GSE56036 database, miR-30a-5p expression was identified to be downregulated in NSCLC. Further investigations showed that overexpression of miR-30a-5p inhibited cell proliferation, migration, and promoted apoptosis in NSCLC. Increase of miR-30a-5p level could induce the increase of Bax protein level and decrease of Bcl-2 protein level. In addition, chromatin immunoprecipitation assays showed that miR-30a-5p expression was induced by binding of p53 to the promoter of MIR30A. Bioinformatics prediction indicated that miR-30a-5p targets SOX4, and western blot analysis indicated that overexpression of the miRNA decreases the SOX4 protein expression level, which in turn regulated the level of p53. Thus, this study provides evidence for the existence of a p53/miR-30a-5p/SOX4 feedback loop, which likely plays a key role in the regulation of proliferation, apoptosis, and migration in NSCLC, highlighting a new therapeutic target.
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Carcinoma Pulmonar de Células não Pequenas/genética , MicroRNAs/genética , Fatores de Transcrição SOXC/genética , Proteína Supressora de Tumor p53/genética , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Transição Epitelial-Mesenquimal/genética , Retroalimentação Fisiológica , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/genéticaRESUMO
INTRODUCTION: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterised by new bone formation, and Dickkopf homologue 1 (Dkk-1) may contribute to the ankylosis of the sacroiliac joint as a main regulator of the Wingless (Wnt) pathway. Increasing evidence shows that microRNAs targeting Dkk-1 might play a critical role in the pathogenesis of rheumatic diseases. We aim to investigate alterations in expression of miRNAs targeting Dkk-1 in AS patients in this study. MATERIAL AND METHODS: The peripheral blood mononuclear cells (PBMCs) of 20 AS patients and 20 normal controls were collected in our study. Three miRNAs targeting DKK1 including miR-29a, miR-335, and miR-363 were selected and quantitative real-time PCR was used to identify the expression of the three miRNAs in these samples. Correlation analysis was conducted between altered miRNA expression and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Function Index (BASFI), and mSASSS (modified Stoke Ankylosing Spondylitis Spinal Score). RESULTS: The expression of miR-29a was significantly higher in AS patients than in healthy controls (p < 0.01), while no significance was observed in the expression of miR-335 and miR-363 between AS patients and healthy controls (p > 0.05). No correlation was observed between miR-29a and ESR, CRP, BASDAI, and BASFI (p > 0.05). The elevated miR-29a expression was correlated with disease duration and mSASSS (p < 0.05). CONCLUSIONS: MiR-29a might be a useful marker in AS new bone formation and contributes to the regulation of Dkk-1 in Wnt signalling.
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Genome-wide association studies (GWAS) of lung cancer in Asian never-smoking women have previously identified six susceptibility loci associated with lung cancer risk. To further discover new susceptibility loci, we imputed data from four GWAS of Asian non-smoking female lung cancer (6877 cases and 6277 controls) using the 1000 Genomes Project (Phase 1 Release 3) data as the reference and genotyped additional samples (5878 cases and 7046 controls) for possible replication. In our meta-analysis, three new loci achieved genome-wide significance, marked by single nucleotide polymorphism (SNP) rs7741164 at 6p21.1 (per-allele odds ratio (OR) = 1.17; P = 5.8 × 10(-13)), rs72658409 at 9p21.3 (per-allele OR = 0.77; P = 1.41 × 10(-10)) and rs11610143 at 12q13.13 (per-allele OR = 0.89; P = 4.96 × 10(-9)). These findings identified new genetic susceptibility alleles for lung cancer in never-smoking women in Asia and merit follow-up to understand their biological underpinnings.
Assuntos
Loci Gênicos , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Povo Asiático , Estudos de Casos e Controles , Cromossomos Humanos Par 12 , Cromossomos Humanos Par 6 , Cromossomos Humanos Par 9 , Feminino , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Razão de Chances , FumarRESUMO
Genome-wide association studies have successfully identified a subset of common variants associated with lung cancer risk. However, these variants explain only a fraction of lung cancer heritability. It has been proposed that low-frequency or rare variants might have strong effects and contribute to the missing heritability. To assess the role of low-frequency or rare variants in lung cancer development, we analyzed exome chips representing 1,348 lung cancer subjects and 1,998 control subjects during the discovery stage and subsequently evaluated promising associations in an additional 4,699 affected subjects and 4,915 control subjects during the replication stages. Single-variant and gene-based analyses were carried out for coding variants with a minor allele frequency less than 0.05. We identified three low-frequency missense variants in BAT2 (rs9469031, c.1544C>T [p.Pro515Leu]; odds ratio [OR] = 0.55, p = 1.28 × 10(-10)), FKBPL (rs200847762, c.410C>T [p.Pro137Leu]; OR = 0.25, p = 9.79 × 10(-12)), and BPIFB1 (rs6141383, c.850G>A [p.Val284Met]; OR = 1.72, p = 1.79 × 10(-7)); these variants were associated with lung cancer risk. rs9469031 in BAT2 and rs6141383 in BPIFB1 were also associated with the age of onset of lung cancer (p = 0.001 and 0.006, respectively). BAT2 and FKBPL at 6p21.33 and BPIFB1 at 20q11.21 were differentially expressed in lung tumors and paired normal tissues. Gene-based analysis revealed that FKBPL, in which two independent variants were identified, might account for the association with lung cancer risk at 6p21.33. Our results highlight the important role low-frequency variants play in lung cancer susceptibility and indicate that candidate genes at 6p21.33 and 20q11.21 are potentially biologically relevant to lung carcinogenesis.
Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Neoplasias Pulmonares/genética , Povo Asiático , Autoantígenos/genética , Cromossomos Humanos Par 20/genética , Cromossomos Humanos Par 6/genética , Proteínas de Ligação a Ácido Graxo , Feminino , Frequência do Gene , Genótipo , Humanos , Imunofilinas/genética , Neoplasias Pulmonares/patologia , Masculino , Proteínas/genética , Fatores de Risco , Proteínas de Ligação a TacrolimoRESUMO
BACKGROUND: The aberrant regulation of MALAT1 has been indicated to be involved in various carcinogenic pathways contributing to the tumourigenesis and progression of cancers. The current meta-analysis summarized the research advances of MALAT1 functions and analyzed its prognostic value among multiple types of cancers. METHODS: Eligible studies were identified through retrieving the PubMed, Web of Science, and CNKI databases, up to Mar 1, 2018. 28 studies of 5436 patients and 36 studies of 3325 patients were enrolled in the meta-analysis to evaluate the association of MALAT1 expression with survival outcomes and clinical parameters. RESULTS: The results demonstrated that over-expression of MALAT1 may predict lymph node metastasis (pooled OR = 2.335, 95% CI 1.606-3.395, P = 0.000) and distant metastasis (pooled OR = 2.456, 95% CI 1.407-4.286, P = 0.002). Moreover, MALAT1 was also related with tumour size (pooled OR = 1.875, 95% CI 1.257-2.795, P = 0.002) and TNM stage (pooled OR = 2.034, 95% CI 1.111-3.724, P = 0.021). Additionally, elevated MALAT1 expression could predict poor OS (pooled HR = 2.298, 95% CI 1.953-2.704, P = 0.000), DFS (pooled HR = 2.036, 95% CI 1.240-3.342, P = 0.005), RFS (pooled HR = 2.491, 95% CI 1.505-4.123, P = 0.000), DSS (pooled HR = 2.098, 95% CI 1.372-3.211, P = 0.001) and PFS (pooled HR = 1.842, 95% CI 1.138-2.983, P = 0.013) in multivariate model. Importantly, subgroup analyses disclosed that increased MALAT1 expression had a poor OS among different cancer types (Estrogen-dependent cancer: pooled HR = 2.656, 95% CI 1.560-4.523; urological cancer: pooled HR = 1.952, 95% CI 1.189-3.204; glioma: pooled HR = 2.315, 95% CI 1.643-3.263; digestive cancer: pooled HR = 2.451, 95% CI 1.862-3.227). CONCLUSIONS: The present findings demonstrated that MALAT1 may be a novel biomarker for predicting survival outcome, lymph node metastasis and distant metastasis.