Our recently published study discovers that exosomal microRNA (miR)-186-5p promotes vascular smooth muscle cell viability and invasion to facilitate atherosclerosis. This research aimed to explore the prognostic implication of serum exosomal miR-186-5p in acute myocardial infarction (AMI) patients receiving percutaneous coronary intervention (PCI).
Abstract Background This study aimed to investigate the plasma long noncoding RNA metastasis‐associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) expression with risk, severity, inflammation level, and prognosis in sepsis. Methods One hundred and ninety sepsis patients and 190 health controls (HCs) were consecutively recruited. Blood samples within 24 hours after admission of sepsis patients and those on enrollment of HCs were collected, and then, plasma was separated for lncRNA MALAT1 and miR‐125b expressions detections by RT‐qPCR. In sepsis patients, clinical data and 28‐day mortality were recorded, and plasma inflammatory cytokines expressions were detected by ELISA. Results Plasma lncRNA MALAT1 expression was elevated in sepsis patients than HCs ( P < 0.001), and ROC curve disclosed that it had a good value in predicting sepsis risk with an area under curve (AUC) of 0.823 (95% CI: 0.783‐0.864). Additionally, lncRNA MALAT1 expression was positively correlated with Scr ( P = 0.005), WBC ( P = 0.017), CRP ( P < 0.001), PCT ( P < 0.001), TNF‐α ( P < 0.001), IL‐8 ( P < 0.001), IL‐17 ( P = 0.001), APACHE II score ( P < 0.001), and SOFA score ( P < 0.001). LncRNA MALA1 expression was elevated in deaths compared with survivors ( P < 0.001) and could predict the risk of 28‐day mortality with an AUC of 0.755 (95% CI: 0.682‐0.828). Accumulating survival was worse in patients with lncRNA MALAT1 high expression compared with patients who had lncRNA MALAT1 low expression ( P < 0.001). Moreover, lncRNA MALAT1 expression was negatively correlated with miR‐125b level in both sepsis patients ( P < 0.001) and HCs ( P < 0.001). Conclusion LncRNA MALAT1 could be developed as a potential biomarker for facilitating diagnosis and management in sepsis patients.
Abstract Objective The present study aimed to investigate the potential value of long non‐coding RNA metastasis‐associated lung adenocarcinoma transcript 1 (lnc‐MALAT1)/microRNA (miR)‐125a axis in disease management and prognosis surveillance of sepsis. Methods Totally, 196 sepsis patients and 196 healthy controls were enrolled. Blood samples were collected within 24 hours after admission in sepsis patients and were collected at enrollment in healthy controls. The relative expression of lnc‐MALAT1 and miR‐125a in all participants was detected by reverse transcription quantitative polymerase chain reaction, and the inflammatory cytokines in plasma of sepsis patients were measured by enzyme‐linked immunosorbent assay. Results Lnc‐MALAT1/miR‐125a axis was increased in sepsis patients compared with healthy controls ( P < .001) and was of excellent value in distinguishing septic patients from healthy controls with the area under the curve (AUC) of 0.931 (95% CI: 0.908‐0.954). In sepsis patients, lnc‐MALAT1 was negatively associated with miR‐125a, and lnc‐MALAT1/miR‐125a axis was positively correlated with acute pathologic and chronic health evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, serum creatinine, C‐reactive protein, tumor necrosis factor‐α, interleukin (IL)‐1β, IL‐6, and IL‐8, while negatively associated with albumin. Furthermore, lnc‐MALAT1/miR‐125a axis was of value in predicting increased 28‐day mortality risk to some extent (AUC: 0.678, 95% CI: 0.603‐0.754). Conclusion Lnc‐MALAT1/miR‐125a axis presents excellent value in differentiating sepsis patients from healthy controls and also exhibits positive association with general disease severity, organ injury, inflammation level, and mortality in sepsis patients.
This study aimed at determining the relationship between baseline cystatin C levels and coronavirus disease 2019 (COVID-19) and investigating the potential prognostic value of serum cystatin C in adult patients with COVID-19. 481 patients with COVID-19 were consecutively included in this study from January 2, 2020, and followed up to April 15, 2020. All clinical and laboratory data of COVID-19 patients with definite outcomes were reviewed. For every measure, COVID-19 patients were grouped into quartiles according to the baseline levels of serum cystatin C. The highest cystatin C level was significantly related to more severe inflammatory conditions, worse organ dysfunction, and worse outcomes among patients with COVID-19 (P values < 0.05). In the adjusted logistic regression analyses, the highest cystatin C level and ln-transformed cystatin C levels were independently associated with the risks of developing critically ill COVID-19 and all-cause death either in overall patients or in patients without chronic kidney disease (P values < 0.05). As a potential inflammatory marker, increasing baseline levels of serum cystatin C might independently predict adverse outcomes for COVID-19 patients. Serum cystatin C could be routinely monitored during hospitalization, which showed clinical importance in prognosticating for adult patients with COVID-19.
Objective To investigate the mechanisms of Chlamydia pneumoniae (C. pn)-induced foam cell formation, the expression of ATP binding cassette transporter AI ( ABCA1 ) and perexisome prolif-erator-activated receptor γ (PPARγ) were examined. Methods THP-1 monneytes were induced into mac-rophages after the addition of 160 nmol/L phorbol myristate acetate (PMA) for 72 h. THP-1-dorived macro-phages when co-cuhured 50 mg/L low density lipoprotein (LDL) were designated randomly in four groups: control (uninfected) group, C. pn infection group, rosiglitazone + C. pn infection group and rosiglitazone group. Lipid droplets in cytoplasm were observed by oil red O staining. The contents of intracellnlur choles-terol ester were detected by enzyme-flnoreseence. The expression of ABCA1, PPARγ, mRNA and protein were determined by RT-PCR and Western blot, respectively. Results C. pn down-regulated the expression of ABCA1, PPARγ at mRNA and protein levels in a concentration-dependent manner in THP-1-derived mac-rophages when co-incubated with LDL. Resiglitazone not only concentration-dependently alleviated the down-regulation of ABCA1 expression by C. pn infection (P<0.05), but also markedly suppressed the accumula- tion of lipid droplets and cholesteryl ester by C. pn at higher concentrations ( 10 and 20 μaol/L). Condu-sion C. pn induces foam cell formation by down-regulating the expression of ABCA1 via PPART pathway, which may provide a new evidence for the development and progression of atherosclerosis initiated by C. pn infection.
Key words:
Chlamydia pneumon/ae; ATP binding cassette transporter AI ; Peroxisome prnlifera-tor-activated receptor γ; Foam cell formation; Atherosclerosis
Abstract Long noncoding RNAs (lncRNAs) are known to play a key role in chronic myelocytic leukemia (CML) development, and we aimed to identify the involvement of the lncRNA HOX antisense intergenic RNA (HOTAIR) in CML via binding to DNA methyltransferase 1 (DNMT1) to accelerate methylation of the phosphatase and tensin homolog (PTEN) gene promoter. Bone marrow samples from CML patients and normal bone marrow samples from healthy controls were collected. HOTAIR, DNMT1, DNMT3A, DNMT3B, and PTEN expression was detected. The biological characteristics of CML cells were detected. The relationship among HOTAIR, DNMT1, and PTEN was verified. Tumor volume and weight in mice injected with CML cells were tested. We found that HOTAIR and DNMT1 expression was increased and PTEN expression was decreased in CML. We also investigated whether downregulated HOTAIR or DNMT1 reduced proliferation, colony formation, invasion, and migration and increased the apoptosis rate of CML cells. Moreover, we tested whether low expression of HOTAIR or DNMT1 reduced the volume and weight of tumors in mice with CML. Collectively, the results of this studied showed that depleted HOTAIR demonstrated reduced binding to DNMT1 to suppress CML progression, which may be related to methylation of the PTEN promoter.
Abstract Background Acute myeloid leukemia (AML) is the most common type of leukemia in adults. Its therapy has not significantly improved during the past four decades despite intense research efforts. New molecularly targeted therapies are in great need. The proto-oncogene c-Myc (MYC) is an attractive target due to its transactivation role in multiple signaling cascades. Deregulation of the MYC is considered one of a series of oncogenic events required for tumorigenesis. However, limited knowledge is available on which mechanism underlie MYC dysregulation and how long non-coding RNAs (lncRNAs) are involved in MYC dysregulation in AML. Methods AML microarray chips and public datasets were screened to identify novel lncRNA GAS6-AS1 was dysregulated in AML. Gain or loss of functional leukemia cell models were produced, and in vitro and in vivo experiments were applied to demonstrate its leukemogenic phenotypes. Interactive network analyses were performed to define intrinsic mechanism. Results We identified GAS6-AS1 was overexpressed in AML, and its aberrant function lead to more aggressive leukemia phenotypes and poorer survival outcomes. We revealed that GAS6-AS1 directly binds Y-box binding protein 1 (YBX1) to facilitate its interaction with MYC, leading to MYC transactivation and upregulation of IL1R1, RAB27B and other MYC target genes associated with leukemia progression. Further, lentiviral-based GAS6-AS1 silencing inhibited leukemia progression in vivo. Conclusions Our findings revealed a previously unappreciated role of GAS6-AS1 as an oncogenic lncRNA in AML progression and prognostic prediction. Importantly, we demonstrated that therapeutic targeting of the GAS6-AS1/YBX1/MYC axis inhibits AML cellular propagation and disease progression. Our insight in lncRNA associated MYC-driven leukemogenesis may contribute to develop new anti-leukemia treatment strategies.
Long non-coding RNAs (lncRNAs) play key roles in various cellular contexts and diseases by diverse mechanisms. With the rapid growth of identified lncRNAs and disease-associated single nucleotide polymorphisms (SNPs), there is a great demand to study SNPs in lncRNAs. Aiming to provide a useful resource about lncRNA SNPs, we systematically identified SNPs in lncRNAs and analyzed their potential impacts on lncRNA structure and function. In total, we identified 495,729 and 777,095 SNPs in more than 30,000 lncRNA transcripts in human and mouse, respectively. A large number of SNPs were predicted with the potential to impact on the miRNA-lncRNA interaction. The experimental evidence and conservation of miRNA-lncRNA interaction, as well as miRNA expressions from TCGA were also integrated to prioritize the miRNA-lncRNA interactions and SNPs on the binding sites. Furthermore, by mapping SNPs to GWAS results, we found that 142 human lncRNA SNPs are GWAS tagSNPs and 197,827 lncRNA SNPs are in the GWAS linkage disequilibrium regions. All these data for human and mouse lncRNAs were imported into lncRNASNP database (http://bioinfo.life.hust.edu.cn/lncRNASNP/), which includes two sub-databases lncRNASNP-human and lncRNASNP-mouse. The lncRNASNP database has a user-friendly interface for searching and browsing through the SNP, lncRNA and miRNA sections.
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