Clinical value of BRE-AS1 in myocardial infarction and its role in myocardial infarction-induced cardiac muscle cell apoptosis.

Objectives. The aim of this study was to investigate the expression of long non-coding RNA (lncRNA) brain and reproductive organ-expressed protein (BRE) antisense RNA 1 (BRE-AS1) in patients with acute myocardial infarction (AMI) and its effect on ischemia/reperfusion (I/R)-induced oxidative stress and apoptosis of cardiomyocytes. Methods. Serum BRE-AS1 levels in patients with AMI was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic and prognostic values of BRE-AS1 were evaluated. H9c2 cells were treated with hypoxia/reoxygenation to establish an in vitro myocardial infarction cell model. The levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). Levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were determined by commercial kits. Cell counting kit-8 (CCK-8) and flow cytometry were used to evaluate the cell viability and cell apoptosis. Results. The expression of BRE-AS1 in serum of patients with AMI is upregulated, which shows the clinical diagnostic value for AMI. In the I/R injury cell model, the knockout of BRE-AS1 can significantly alleviate the increase in TNF-α, IL-1ß, and IL-6 levels, inhibit the production of LDH and MDA, increase the activities of SOD and GSH-Px, promote the cell viability and suppress cell apoptosis. Conclusions. Abnormally elevated BRE-AS1 has a high diagnostic value for AMI as well as a prognostic value for major adverse cardiovascular events (MACEs). The elevation of BRE-AS1 promoted oxidative stress injury and cell apoptosis in vitro.

The clinical significance of long non-coding RNAs MALAT1 and CASC2 in the diagnosis of HCV-related hepatocellular carcinoma.

BACKGROUND: Globally, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death due to a lack of early predictive and/or diagnostic tools. Thus, research for a new biomarker is important. LncRNAs play a functional role in target gene regulation and their deregulation is associated with several pathological conditions including HCC. OBJECTIVE: This study aimed to explore the diagnostic potential of two LncRNAs MALAT1 and CASC2 in HCC compared to the routinely used diagnostic biomarker. MATERIALS AND METHODS: The current study is a case-control study carried out at Fayoum University Hospital and conducted on 89 individuals. The study included three groups of 36 HCC patients on top of HCV(HCC/HCV), 33 HCV patients, and 20 healthy volunteers as a control group. All study subjects were subjected to radiological examinations. The determination of CBC was performed by the automated counter and liver function tests by the enzymatic method were performed. In addition, HCV RNA quantification and the expression level of two LncRNAs (MALAT1 and CASC2) were performed by qRT-PCR. RESULTS: The results revealed a statistically significant difference between study groups regarding liver function tests with a higher mean in HCC/HCV group. Also, serum MALAT1 significantly up-regulated in HCV (11.2±2.8) and HCC/HCV (4.56±1.4) compared to the control group. Besides, serum CASC2 levels in the HCV group were significantly upregulated (14.9±3.6), while, downregulated in the HCC group (0.16± 0.03). Furthermore, The ROC analysis for diagnostic efficacy parameters indicated that CASC2 has higher accuracy (94.6%) and sensitivity (97.2%) for HCC diagnosis than AFP with an accuracy of (90.9%), sensitivity (69.4%), and MALAT1 showed an accuracy of (56.9%), sensitivity (72.2%). CONCLUSION: Our study results indicated that CASC2 is a promising biomarker and is considered better and could help in HCC diagnosis on top of HCV than MALAT1 and the routine biomarker AFP.

Common variation in a long non-coding RNA gene modulates variation of circulating TGF-ß2 levels in metastatic colorectal cancer patients (Alliance).

BACKGROUND: Herein, we report results from a genome-wide study conducted to identify protein quantitative trait loci (pQTL) for circulating angiogenic and inflammatory protein markers in patients with metastatic colorectal cancer (mCRC). The study was conducted using genotype, protein marker, and baseline clinical and demographic data from CALGB/SWOG 80405 (Alliance), a randomized phase III study designed to assess outcomes of adding VEGF or EGFR inhibitors to systemic chemotherapy in mCRC patients. Germline DNA derived from blood was genotyped on whole-genome array platforms. The abundance of protein markers was quantified using a multiplex enzyme-linked immunosorbent assay from plasma derived from peripheral venous blood collected at baseline. A robust rank-based method was used to assess the statistical significance of each variant and protein pair against a strict genome-wide level. A given pQTL was tested for validation in two external datasets of prostate (CALGB 90401) and pancreatic cancer (CALGB 80303) patients. Bioinformatics analyses were conducted to further establish biological bases for these findings. RESULTS: The final analysis was carried out based on data from 540,021 common typed genetic variants and 23 protein markers from 869 genetically estimated European patients with mCRC. Correcting for multiple testing, the analysis discovered a novel cis-pQTL in LINC02869, a long non-coding RNA gene, for circulating TGF-ß2 levels (rs11118119; AAF = 0.11; P-value < 1.4e-14). This finding was validated in a cohort of 538 prostate cancer patients from CALGB 90401 (AAF = 0.10, P-value < 3.3e-25). The analysis also validated a cis-pQTL we had previously reported for VEGF-A in advanced pancreatic cancer, and additionally identified trans-pQTLs for VEGF-R3, and cis-pQTLs for CD73. CONCLUSIONS: This study has provided evidence of a novel cis germline genetic variant that regulates circulating TGF-ß2 levels in plasma of patients with advanced mCRC and prostate cancer. Moreover, the validation of previously identified pQTLs for VEGF-A, CD73, and VEGF-R3, potentiates the validity of these associations.

Diagnostic value and clinical significance of lncRNA LINC01123 combined with fibrinogen in acute cerebral infarction.

OBJECTIVE: To explore the diagnostic value and clinical significance of lncRNA LINC01123 (LINC01123) binding fibrinogen in acute cerebral infarction (ACI) by evaluating the expression and potential molecular mechanism of LINC01123 in patients with acute cerebral infarction. METHODS: The clinical data of all the volunteers were collected. The level of serum LINC01123 in ACI patients was detected by RT-qPCR. The relationship between LINC01123 and fibrinogen was studied via Pearson's correlation analysis. ROC curve was used to evaluate the diagnostic value of LINC01123 and fibrinogen for ACI. The risk factors of ACI were investigated by Binary Logistic regression analysis. And the targeting relationship between LINC01123 and downstream miR-361-3p was verified through luciferase activity assay. RESULTS: Serum LINC01123 and fibrinogen levels were upregulated in ACI patients compared with healthy controls (P < 0.001), and there was a positive correlation between them (r = 0.6537, P < 0.001). In predicting the occurrence of ACI, LINC01123 and fibrinogen have high diagnostic value, and the AUC of combined diagnosis was 0.961, and the sensitivity and specificity (92.54%, 85.82%) were more significant. Meanwhile, LINC01123 and fibrinogen were confirmed to be independent risk factors for ACI (P < 0.0001). Mechanistically, miR-361-3p is the target of LINC01123. The expression of miR-361-3p was low in the serum of ACI patients, which was negatively correlated with the LINC01123 expression (r = -0.6885, P < 0.0001). CONCLUSION: LINC01123 combined with fibrinogen may have important reference value in the diagnosis of ACI as serum markers, which may become clinical indicators to predict the occurrence of ACI.

LncRNA microarray profiling identifies novel circulating lncRNAs in hidradenitis suppurativa.

Long noncoding RNAs (lncRNAs) have been demonstrated to be involved in biological processes, both physiological and pathological, including cancer, cardiovascular diseases, multiple sclerosis, autoimmune hepatitis and types I and II diabetes. LncRNAs are also known to have a critical role in the physiology of skin, and in the pathology of cutaneous diseases. LncRNAs are involved in a wide range of biological activities, including transcriptional post­transcriptional processes, epigenetics, RNA splicing, gene activation and or silencing, modifications and/or editing; therefore, lncRNAs may be useful as potential targets for disease treatment. Hidradenitis suppurativa (HS), also termed acne inversa, is a major skin disease, being an inflammatory disorder that affects ~1% of global population in a chronic manner. Its pathogenesis, however, is only partly understood, although immune dysregulation is known to have an important role. To investigate the biological relevance of lncRNAs with HS, the most differentially expressed lncRNAs and mRNAs were first compared. Furthermore, the lncRNA­microRNA regulatory network was also defined via reverse transcription­quantitative PCR analysis, whereby a trio of lncRNA expression signatures, lncRNA­TINCR, lncRNA­RBM5­ASI1 and lncRNA­MRPL23­AS1, were found to be significantly overexpressed in patients with HS compared with healthy controls. In conclusion, the three lncRNAs isolated in the present study may be useful for improving the prognostic prediction of HS, as well as contributing towards an improved understanding of the underlying pathogenic mechanisms, thereby potentially providing new therapeutic targets.

A novel diagnostic model based on lncRNA PTPRE expression, neutrophil count and red blood cell distribution width for diagnosis of seronegative rheumatoid arthritis.

Diagnosis of seronegative rheumatoid arthritis (SNRA) is difficult due to the lack of diagnostic markers. The study aims to construct a novel diagnostic model based on long noncoding RNAs (lncRNAs) expression and laboratory indicators to provide a new idea for diagnostic methods of SNRA. Differentially expressed lncRNAs in peripheral blood cells of RA patients were screened through eukaryotic long noncoding RNA sequencing and validated by quantitative real-time PCR. Meanwhile, the correlation between lncRNAs expression and laboratory indicators was analyzed. The diagnostic value was evaluated by receiver operating characteristic curve analysis. Finally, combined with laboratory indicators, a diagnostic model for SNRA was constructed based on logistic regression and visualized by nomogram. Expression of ADGRE5, FAM157A, PTPN6 and PTPRE in peripheral blood was significantly increased in RA than healthy donors. Meanwhile, we analyzed the relationship between lncRNAs and erythrocyte sedimentation rate, C-reactive protein and CD4 + T cell-related cytokines and transcription factors. Results showed that FAM157A and PTPN6 were positively related to RORγt, and negatively related to GATA3. Moreover, PTPRE has potential discrimination ability between SNRA and healthy donor (AUC = 0.6709). Finally, we constructed a diagnostic model based on PTPRE, neutrophil count and red blood cell distribution width (RDW). The AUC of the model was 0.939 and well-fitted calibration curves. Decision curve analysis indicated the model had better predict performance in SNRA diagnosis. Our study constructed a novel diagnostic model based on PTPRE, neutrophil count and RDW which may serve as a potential tool for the diagnosis of SNRA.

Long noncoding RNAs (CTC-471J1.2, NeST) as epigenetic risk factors of active juvenile lupus nephritis: a case-control study.

BACKGROUND: Measurement of the circulating levels of long-non-coding RNAs (lncRNAs) in lupus nephritis (LN) patients could dramatically explore more insights about the disease pathogenesis. Hence, we aimed to quantify the level of expression of CTC-471J1.2 and NeST in LN patients and to correlate it with the disease activity. METHOD: This case-control study was conducted on a group of children with juvenile LN attending to Mansoura University Children's Hospital (MUCH). Demographics, clinical, and laboratory findings were collected besides the measurement of lncRNAs by quantitative real-time PCR. RESULTS: The expression level of lncRNAs-CTC-471J1.2 was significantly down-regulated in children with active LN versus inactive cases or controls. In contrast, the NeST was significantly up-regulated in active LN cases. A significant correlation was found between CTC-471J1.2 expression and LN activity parameters. Additionally, both lncRNAs showed a reasonable sensitivity and specificity in differentiation of active LN. A regression analysis model revealed that CTC-471J1.2 and NeST were independent predictors of active nephritis. CONCLUSION: The expression level of circulatory lncRNAs-CTC-471J1.2 and NeST can be used as sensitive and specific biomarkers for active LN. Furthermore, both could serve as predictors for nephritis activity.

Expression of PVT-1 and miR-29a/29b as reliable biomarkers for liver cirrhosis and their correlation with the inflammatory biomarkers profile.

BACKGROUND & AIMS: The liver is a vital organ responsible for numerous metabolic processes, which can be significantly impacted by long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). These ribonucleic acid (RNA) molecules have been shown to play a crucial role in regulating gene expression, and their dysregulation has been implicated in numerous liver disorders. Our study aimed to investigate the diagnostic accuracy of plasmacytoma variant translocation-1 (PVT-1), microRNA-29a/29b (miR-29a/miR-29b), and inflammatory biomarkers [ interleukine-6 (IL-6), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-ß), and insulin growth factor-1 (IGF-1)] as diagnostic and prognostic biomarkers for liver cirrhosis. Therefore, understanding the mechanisms by which lncRNAs and miRNAs influence liver metabolism is of paramount importance in developing effective treatments for liver-related diseases. METHODS: Serum samples were collected from 164 participants, comprising 114 cirrhotic patients with varying grades (35 grade I, 35 grade II, and 44 grade III) and 50 healthy controls. PVT-1 and miR-29a/miR-29b expression was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-PCR), while the serum levels of inflammatory biomarkers were assessed using enzyme-linked immunosorbent assay (ELISA). RESULTS: The study participants exhibited notable differences in PVT-1 and miR-29a/miR-29b expression. ROC analysis revealed excellent discriminative power for PVT-1 and miR-29a/miR-29b in distinguishing cirrhotic patients from healthy controls. CONCLUSION: This study demonstrates the promising potential of PVT-1 and miR-29a/miR-29b as early diagnostic biomarkers for liver cirrhosis detection, requiring further validation in larger cohorts. Our findings also reinforce the diagnostic value of circulating inflammatory biomarkers (IL-6, TNF-α, TGF-ß, and IGF-1) levels for liver cirrhosis screening.

Insights into the Crosstalk Between miR-200a/lncRNA H-19 and IL-6/SIRT-1 Axis in Breast Cancer.

Breast cancer (BC) is a highly prevalent malignancy that poses a significant threat to women's well-being. Novel biomarker identification helps to improve clinical outcomes and provide tailored treatments. Our research aims to explore the diagnostic potential of miR-200a/lncRNA H-19 and interleukin-6 (IL-6)/SIRT-1 axis crosstalk and evaluate the impact of metastasis on gene expression, which provides valuable insights into the diagnosis and treatment of BC. In this case-control study, we collected blood samples from 54 nonmetastatic breast cancer (NMBC) patients, 46 metastatic breast cancer (MBC) patients, and 50 healthy individuals. We used real time-polymerase chain reaction to measure the expression levels of lncRNA H-19 and miR-200a, whereas enzyme linked immunosorbent assay was used to determine the IL-6 levels. In addition, we evaluated SIRT-1 expression level using a Western blot assay. The levels of lncRNA H-19, miR-200a, and IL-6 were higher in BC patients, whereas SIRT-1 levels were lower. Patients with MBC had higher levels of lncRNA H-19, miR-200a, and IL-6 than those with NMBC. In addition, the expression of lncRNA H-19 and miR-200a showed a negative correlation with SIRT-1 expression, whereas the levels of lncRNA H-19 and miR-200a showed a positive correlation with IL-6 expression level. The diagnostic potential of lncRNA H-19 and miR-200a in BC is undeniable. Moreover, the robust association of IL-6/SIRT-1 with lncRNA H-19/miR-200a expression presents a promising opportunity for clinical outcomes and tailored treatments.

Liquid Biopsy for Pancreatic Cancer by Serum Extracellular Vesicle-Encapsulated Long Noncoding RNA HEVEPA.

OBJECTIVES: The role of long noncoding RNAs (lncRNAs) in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Extracellular vesicle (EV)-encapsulated RNAs could be effective targets for liquid biopsy. We aimed to identify previously unknown EV-encapsulated lncRNAs in PDAC and establish highly accurate methods for isolating EVs. MATERIALS AND METHODS: Extracellular vesicles were isolated using existing and newly developed methods, namely, PEViA-UC and PEViA-IP, from serum samples of 20 patients with PDAC, 22 patients with intraductal papillary mucinous neoplasms, and 21 healthy individuals. Extracellular vesicle lncRNA expression was analyzed using digital PCR. RESULTS: Gene expression analysis using cDNA microarray revealed a highly expressed lncRNA, HEVEPA , in serum EVs from patients with PDAC. We established PEViA-UC and PEViA-IP using PEViA reagent, ultracentrifugation, and immunoprecipitation. Although detection of EV-encapsulated HEVEPA using existing methods is challenging, PEViA-UC and PEViA-IP detected EV HEVEPA , which was highly expressed in patients with PDAC compared with non-PDAC patients. The detection sensitivity for discriminating PDAC from non-PDAC using the combination of HEVEPA and HULC , which are highly expressed lncRNAs in PDAC, and carbohydrate antigen 19-9 (CA19-9), was higher than that of HEVEPA , HULC , or CA19-9 alone. CONCLUSIONS: Extracellular vesicle lncRNAs isolated using PEViA-IP and CA19-9 together could be effective targets in liquid biopsy for PDAC diagnosis.

Exosomal noncoding RNAs as noninvasive biomarkers in bladder cancer: a diagnostic meta-analysis.

BACKGROUND: In view of discordance consisting in different reports, a meta-analysis was conducted to comprehensively evaluate the diagnostic efficacy of exosomal noncoding RNAs (ncRNAs) in blood and urine in the detection of bladder cancer. METHODS: Eligible studies were acquired by systematic retrieval through PubMed, Cochrane Library, and Embase. The pooled diagnostic efficacy was appraised by reckoning the area under the summary receiver operating characteristic (SROC) curve. The latent sources of heterogeneity were probed by subgroup analyses and meta-regression. STATA 12.0, Meta-DiSc 1.4, and RevMan 5.3 were applied to carry out all statistical analyses and plots. RESULTS: A total of 46 studies from 15 articles comprising 2622 controls and 3015 bladder cancer patients were included in our meta-analysis. Exosomal ncRNAs in blood and urine represented relatively satisfactory diagnostic efficacy in detecting bladder cancer, with a pooled sensitivity of 0.75, a specificity of 0.79, and an area under the SROC curve (AUC) of 0.84. Exosomal microRNAs (miRNAs) exhibited better diagnostic value with a pooled AUC of 0.91 than that of exosomal long noncoding RNAs (lncRNAs). To some extent, the heterogeneity among studies was induced by exosomal ncRNA types (miRNA or lncRNA), exosomal ncRNA profiling (single- or multiple-ncRNA), sample size, specimen types, and ethnicity. CONCLUSION: Exosomal ncRNAs in blood and urine may play a vital role in diagnosing bladder cancer as prospective noninvasive biomarkers; nonetheless, their clinical performance needs to be confirmed by further massive proactive researches.

Plasma long non-coding RNAs ASMTL-AS1, AP001363.1, AC005730.3 and AL133415.1 as a potential biomarker for Alzheimer's disease.

BACKGROUND: Long non-coding RNAs (lncRNAs) play critical role in the pathogenesis of neurodegenerative diseases. Human plasma contains lncRNAs that are present in the blood, and their disease-specific profile has been considered a potential biomarker in some diseases. METHODS: This study reports screening of the plasma levels of lncRNAs between Alzheimer disease(AD) (n = 45) and matched healthy controls (n = 45). The plasma samples of 5 AD patients and 5 matched healthy controls were randomly selected for expression levels of lncRNAs using the TruSeq RNA Sample Prep Kit (Illumina). The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to study the potential of lncRNAs as biomarkers. RESULTS: The differential expression profiles of plasma showed that 514 lncRNAs were upregulated, whereas 499 lncRNAs were downregulated.We found that the lncRNAs AL133415.1, AC020916.1, ENST00000654948, ASMTL-AS, AC005730.3, and AP001363.1 levels in the plasma of the AD patients were significantly lower compared to the control group (p1 = 0.0006, p2 < 0.001, p3 < 0.001, p4 = 0.039, p5 = 0.006, p6 < 0.001, respectively). ROC curve analysis revealed that the AUC of AL133415.1 was 0.635 (95% CI]: 0.507-0.763, p = 0.036), the AUC of ASMTL-AS1 was 0.658 (95% CI: 0.513-0.785, p = 0.015), the AUC of AC005730.3 was 0.627 (95%CI: 0.498-0.756, p = 0.049), and the AUC of AP001363.1 was 0.708 (95%CI: 0.595-0.822, p = 0.001). CONCLUSION: This study indicated that the plasma levels of the lncRNAs ASMTL-AS1, AP001363.1, AC005730.3, and AL133415.1 might be considered potential biomarkers for AD in the Chinese Population.

Association between Inflammatory Factors, Vitamin D, Long Non-Coding RNAs, MALAT1, and Adiponectin Antisense in Individuals with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a common clustering of cardiovascular risk factors associated with increased inflammation. Long non-coding RNA (LncRNA) are involved in many of the body's metabolic activities, including inflammation. Vitamin D may play a vital role in preventing metabolic syndrome risk factors. This study aimed to evaluate the status of inflammation and expression of LncRNA and their relationship with serum vitamin D levels in patients with metabolic syndrome. METHOD: This cross-sectional study included staff and Mashhad University of Medical Sciences students between 30 and 50 years old who met the International Diabetes Federation criteria for Mets. Total RNA was extracted from both frozen clinical samples using the Trizol reagent. RESULTS: A total of eighty people were recruited into the two groups, with and without MetS. Inflammatory markers were higher in the individuals in the MetS group, and linear regression showed an inverse association between serum vitamin D and LncRNAs. There was a positive association between inflammatory biomarkers, lipid profiles and Adiponectin Antisense (APQ AS) expression. CONCLUSION: APQ AS and MALAT1 levels are positively associated with inflammatory biomarkers and inverse relation between MALAT1 and serum 25 (OH) D concentration.

Anesthetic­specific lncRNA and mRNA profile changes in blood during colorectal cancer resection: A prospective, matched­case pilot study.

Prometastatic and antitumor effects of different anesthetics have been previously analyzed in several studies with conflicting results. Thus, the underlying perioperative molecular mechanisms mediated by anesthetics potentially affecting tumor phenotype and metastasis remain unclear. It was hypothesized that anesthetic­specific long non­coding RNA (lncRNA) expression changes are induced in the blood circulation and play a crucial role in tumor outcome. In the present study, high­throughput sequencing and quantitative PCR were performed in order to identify lncRNA and mRNA expression changes affected by two therapeutic regimes, total intravenous anesthesia (TIVA) and volatile anesthetic gas (VAG) in patients undergoing colorectal cancer (CRC) resection. Total blood RNA was isolated prior to and following resection and characterized using RNA sequencing. mRNA­lncRNA interactions and their roles in cancer­related signaling of differentially expressed lncRNAs were identified using bioinformatics analyses. The comparison of these two time points revealed 35 differentially expressed lncRNAs in the TIVA­group, and 25 in the VAG­group, whereas eight were shared by both groups. Two lncRNAs in the TIVA­group, and 23 in the VAG­group of in silico identified target­mRNAs were confirmed as differentially regulated in the NGS dataset of the present study. Pathway analysis was performed and cancer relevant canonical pathways for TIVA were identified. Target­mRNA analysis of VAG revealed a markedly worsened immunological response against cancer. In this proof­of­concept study, anesthesic­specific expression changes in lncRNA and mRNA profiles in blood were successfully identified. Moreover, the data of the present study provide the first evidence that anesthesia­induced lncRNA pattern changes may contribute further in the observed differences in CRC outcome following tumor resection.

[Association study of serum LncRNA MALAT1 and SAA with type 2 diabetic kidney disease].

To investigate the correlation of serum long noncoding RNA-metastasis associated lung adenocarcinoma transcript 1(LncRNA MALAT1) and serum amyloid A(SAA) with diabetic kidney disease. Retrospective research was used, and 40 patients with type 2 diabetes and 80 patients with type 2 diabetic kidney disease patients who were treated in Tianjin Medical University Chu Hsien-I Memorial Hospital from August 2021 to February 2022 were selected, and 40 healthy subjects were selected during the same period. Reverse transcription-polymerase chain reaction(RT-PCR) was used to detect serum LncRNA MALAT1. SAA were detected with enzyme linked immunosorbent assay (ELISA). Automatic biochemistry analyzer was used to detect serum creatinine (CREA) and low-density lipoprotein cholesterol(LDL-C),automatic blood glucose analyzer to detect serum fasting plasma glucose (FPG), automatic glycated hemoglobin analyzer to detect hemoglobin A1C (HbA1c), and automatic immunoassay analyzer to detect urinary albumin to creatinine ratio(UACR). Differences between groups were compared by t test and analysis of variance. Pearson analysis was used to analyze the correlation between MALAT1, SAA and other indicators. Receiver operating characteristic curve(ROC) was used to evaluate the auxiliary diagnostic value of MALAT1 and SAA for diabetic kidney disease. The results showed that MALAT1 and SAA in the diabetic kidney disease with mass albuminuria group were higher than those in the type 2 diabetes mellitus group (q=8.57, P<0.01; q=11.09, P<0.01) and the diabetic kidney disease with microalbuminuria group (q=3.96, P<0.05; q=7.85, P<0.01). MALAT1 had a high correlation with UACR, CREA, SAA, HbA1c and FPG (r value was 0.706, 0.643, 0.578, 0.553, and 0.524, all P<0.01), and SAA had a high correlation with UACR, HbA1c and FPG (r value was 0.664, 0.617, and 0.595, all P<0.01). ROC curve analysis of the diagnostic value of LncRNA MALAT1 and protein SAA for diabetic kidney disease showed that the areas under curve (AUC) were 0.741 and 0.744, respectively. The combined diagnostic value of the two was the greatest (AUC=0.801). In summary, MALAT1 and SAA were elevated in the serum of patients with type 2 diabetes. Their concentrations in the serum of group with diabetic kidney disease were higher than that in the type 2 diabetes group, and the serum concentrations of MALAT1 and SAA in group with mass albuminuria are higher than the group with microalbuminuria. MALAT1 and SAA were both closely related to UACR and HbA1c, and there is a correlation between them. Both of them may have ancillary diagnostic value for diabetic kidney disease.

A novel circulating biomarker lnc-MALAT1 for acute myocardial infarction: Its relationship with disease risk, features, cytokines, and major adverse cardiovascular events.

OBJECTIVE: Long noncoding RNA MALAT1 (lnc-MALAT1) modulates atherosclerotic progression, myocardial ischemia injury, and systematic inflammation, which may be closely involved in acute myocardial infarction (AMI) pathogenesis. Thus, the current study intended to explore the relationship of lnc-MALAT1 to disease risk, features, cytokines, and prognostication in AMI patients. METHODS: This multicenter study consecutively enrolled 160 newly diagnosed AMI patients and 50 controls (angina pectoris patients). Their peripheral blood mononuclear cells were obtained to measure lnc-MALAT1 by RT-qPCR. Serum cytokines in AMI patients were detected by ELISA. In addition, AMI patients were followed up for major adverse cardiovascular event (MACE) risk evaluation. RESULTS: Lnc-MALAT1 was higher in AMI patients than in controls (median: 2.245 vs. 0.996, p = 0.004), and it also presented a good capacity for differentiating AMI patients from controls with an area under the curve of 0.823. Lnc-MALAT1 was positively related to C-reactive protein (p = 0.005), low-density lipoprotein cholesterol (p = 0.022), cardiac troponin I (p = 0.021), and infarct size (p = 0.007), but not other biochemical indexes in AMI patients. Meanwhile, lnc-MALAT1 was positively associated with tumor necrosis factor-alpha (p = 0.001), interleukin (IL)-6 (p = 0.031), IL-17A (p = 0.042), vascular cell adhesion molecule-1 (p = 0.004), and intercellular adhesion molecule-1 (p = 0.021) among AMI patients. Importantly, after categorization, lnc-MALAT1 high (vs. low) was related to an elevated MACE accumulation rate (p = 0.035); furthermore, a higher lnc-MALAT1 quartile showed a trend to be linked with an increased MACE accumulation rate (p = 0.092). CONCLUSION: Lnc-MALAT1 may serve as a biomarker for AMI risk, infarct size, inflammation and prognosis, but further validation by large-scale studies is needed.

Highly Expressed lncRNA GAS5 in the Serum of Children with Mycoplasma pneumoniae Pneumonia and Its Effect on LAMPs-Induced Apoptosis and Inflammation.

The aim of the study was to explore the serum expression of long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) in Mycoplasma pneumoniae pneumonia (MPP) and its effect on lipid-associated membrane proteins (LAMPs)-induced apoptosis and inflammation. Totally, 56 children with MPP (MPP group) and 56 healthy children (NC group) were enrolled. lncRNA GAS5 expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Serum levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) were detected using ELISA, and the high mobility family protein B1 (HMGBl) was detected by qRT-PCR. The methylated binding protein 2 (MECP2) was inhibited by gene silencing, and the expression of MECP2, TNF-α, IL-6, HMGBl, p-p65, and p-IκBα was measured. lncRNA GAS5 and TNF-α, IL-6, and HMGBl in the peripheral blood of the MPP group were positively correlated (P < 0.05). The expression of TNF-α, IL-6, HMGBl, and lncRNA GAS5 showed a positive correlation with that of LAMPs. The GAS5-siRNA group showed an increased cell survival rate compared with the scrambled-RNAi group (P < 0.05) while showing decreased apoptosis and cell death rates (P < 0.05). In addition, the expression of IL-6, TNF-α, HMGBl, p-p65, and p-IκBα was significantly reduced (P < 0.05). lncRNA GAS5 is highly expressed in the serum of children with MPP and inhibits LAMPs-induced apoptosis and alveolar macrophage inflammation.

Vitamin D Reduces the Helper T Cells 17 (Th17) Differentiation in Patients with Ulcerative Colitis by Targeting Long Non-coding RNA (lncRNA) OIP5-AS1/miR-26a-5p/IL-6 Axis

BACKGROUND: Vitamin D has anti-inflammatory efficacy against ulcerative colitis (UC), however, the mechanism is yet little understood. OBJECTIVE: To investigate the immunomodulatory effects of vitamin D against the UC, and to explore the potential downstream mechanisms. MATERIALS AND METHODS: Serum vitamin D, Interferon-γ (IFN-γ) and Interleukin (IL)-17 levels of the patients with UC were quantified using enzyme-linked immunosorbent assay (ELISA). Long non-coding RNAs (lncRNAs) levels were determined by using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Peripheral blood mononuclear cells (PBMCs) were collected from healthy control subjects, stimulated with CD4+ T lymphocytes or helper T cells 17(Th17) differentiation conditions, and then exposed to calcitriol (vitamin D active form) or certain lentiviral treatment, followed by subsequent molecular level testing. For in vivo assay, mice were given 3% dextran sulfate sodium (DSS) to induce colitis. RESULTS: Compared with the control group, vitamin D levels in the UCs were statistically lower, and there was a negative correlation between IL-17 and vitamin D in the UCs. The lncRNA OIP5-AS1 could decrease under calcitriol treatment in both CD4+ T cells and Th17 differentiation. The lncRNA OIP5-AS1 was a microRNA (miR)-26a-5p sponge and therefore modulated the Th17 cells and IL-6 expression. The lncRNA OIP5-AS1/miR-26a-5p/IL-6 axis mediated the regulation of calcitriol-induced Th17 differentiation. Calcitriol had therapeutic effects on the UC mouse models by regulating the lncRNA OIP5-AS1 related pathway. CONCLUSION: Vitamin D might have anti-inflammatory potential in the treatment of the UC.

Functional Analysis of Serum Long Noncoding RNAs in Patients with Atrial Fibrillation.

Objectives: Long noncoding RNAs (lncRNAs) are closely related to diverse diseases. However, its role in atrial fibrillation (AF) pathogenesis needs further exploration. Design: We performed microarray analysis on the serum samples from 70 healthy volunteers and 70 AF patients. This study was aimed at detecting the levels of serum lncRNAs and mRNAs and bioinformatically analyze them to establish potential marker(s) for AF diagnosis. Receiver operating curve (ROC) and area under the curve (AUC) were employed to address the AF diagnostic power of lncRNAs. Results: In the AF serum samples, 753 lncRNAs and 802 mRNAs (p ≤ 0.05; fold change ≥ 2) were upregulated, and 315 lncRNAs and 153 mRNAs were downregulated, as opposed to healthy serum samples. Using bioinformatic analysis, we analyzed the top 4 differentially expressed (DE) lncRNAs, namely, NR-001587, NR-015407, NR-038455, and NR-038894, and found that the PI3K-AKT cell proliferation signaling pathway was most affected. This was in accordance with our functional analysis of DE mRNAs and adjacent lncRNAs. Notably, the elevated serum NR-001587 levels were strongly associated with AF incidence. Conclusions: Our work highlights the role of lncRNAs in AF pathogenesis and provides a novel serum biomarker for AF diagnosis.

Plasma lncRNA LOC338963 and mRNA AP3B2 are upregulated in paraneoplastic Lambert-Eaton myasthenic syndrome.

INTRODUCTION/AIMS: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune neuromuscular junction disorder. Long noncoding RNA (lncRNA) can regulate the expression of mRNA and is involved in the development of autoimmune diseases, but few genetic studies are available. In this study we aimed to explore the lncRNA and mRNA changes of LEMS. METHODS: Plasma lncRNA and mRNA expression profiles of three LEMS patients with small cell lung cancer (SCLC) and three matched healthy controls were analyzed by microarray. Differentially expressed lncRNAs and adjacent mRNAs were jointly analyzed, and candidates were verified by quantitative real-time polymerase chain reaction (qRT-PCR). The identified genes were subsequently evaluated in 9, 8, and 4 patients with paraneoplastic LEMS, nontumor LEMS, and SCLC, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine possible functions. RESULTS: A total of 320 lncRNA and 168 mRNAs were differentially expressed in the three LEMS with SCLC and compared with healthy controls. Among these, lncRNA LOC338963 and its neighboring mRNA AP3B2 were upregulated jointly, which was confirmed by qRT-PCR. qRT-PCR revealed significant upregulation of the two genes in patients with paraneoplastic LEMS compared with nontumor LEMS or SCLC. GO analysis of AP3B2 identified the enrichment terms anterograde synaptic vesicle transport and establishment of synaptic vesicle localization. KEEG analysis showed that AP3B2 was enriched in lysosomal pathways. DISCUSSION: LOC338963 and AP3B2 were upregulated in patients with paraneoplastic LEMS, suggesting their involvement in pathogenesis. These genes could be targets for exploring the pathomechanism of paraneoplastic LEMS.