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Long non-coding RNAs (lncRNAs) play a critical role in a variety of human diseases such as cancer. Here, to elucidate a novel function of a lncRNA called LINC00173, we investigated its binding partner, target gene, and its regulatory mechanism in lung adenocarcinoma, including the A549 cell line and patients. In the A549 cell line, RNA immunoprecipitation (RIP) assays revealed that LINC00173 efficiently binds to SNAIL. RNA-seq and RT-qPCR analyses revealed that the expression of FHIT was decreased upon LINC00173 depletion, indicating that FHIT is a target gene of LINC00173. Overexpression of SNAIL suppressed and depletion of SNAIL increased the expression of FHIT, indicating that SNAIL negatively regulates FHIT. The downregulation of FHIT expression upon LINC00173 depletion was restored by additional SNAIL depletion, revealing a LINC00173-SNAIL-FHIT axis for FHIT regulation. Data from 501 patients with lung adenocarcinoma also support the existence of a LINC00173-SNAIL-FHIT axis, as FHIT expression correlated positively with LINC00173 (p = 1.75 × 10−6) and negatively with SNAIL (p = 7.00 × 10−5). Taken together, we propose that LINC00173 positively regulates FHIT gene expression by binding to SNAIL and inhibiting its function in human lung adenocarcinoma. Thus, this study sheds light on the LINC00173-SNAIL-FHIT axis, which may be a key mechanism for carcinogenesis and progression in human lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

We investigated the effects of by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, cerivastatin and fluvastatin, on the induction of nitric oxide (NO) production in vascular smooth muscle cells ( VSMC) stimulated by interleukin-1β (1L-1) or in combination with interferon-γ (IFN). IL-1 activated VSMC to synthesize and release NO, which was significantly potentiated by IFN. NO production induced by IL-1 or IL-1/lFN was dosedependently enhanced by both HMG-CoA reductase inhibitors. Incubating VSMC with IL-1/IFN stimulated inducible NO synthase (iNOS) mRNA expression. Both HMG-CoA reductase inhibitors significantly upreguiated IL/IFN-stimulated iNOS mRNA expression, and enhanced iNOS gene transcription as shown by nuclear run-on assays. Both IIMG-CoA reductase inhibitors slightly modulated IL-1/IFN-induced NF-kB activation, which was not associated with their effect on NO production. Cytokines induce the de novo synthesis of tetrahydrobiopterin (BH4) in VSMC. This event is essential for the induction of NO synthesis, which requires transcriptional induction of the genes that encode not only iNOS but also guanosine triphosphate cyclohydrolase I (GTPCH), the first and rate-limiting enzyme in de novo BH4 synthesis. The synthesis of BH4 and GFPCH mRNA induced by IL-1/IFΝ were enhanced by both HMG-CoA reductase inhibitors. Exogenous mevalonate significantly prevented and geranylgeranylpyrophosphate reversed the stimulatory effect of HMG-CoA reductase inhibitors. Thus, the effect of HMG-CoA reductase inhibitors on NO production is due at least partly through blocking the biosynthesis of mevalonate, which prevents isoprenoid biosynthesis. Our data demonstrated that HMG-CoA reductase inhibitors enhance immunostimulants-induced NO production by increasing iNOS gene expression at the transcriptional level via an NF-kB-independent pathway. In addition to augmenting iNOS expression, HMG-CoA reductase inhibitors potentiate GTPCH gene expression and BH4 synthesis, thereby prevents a relative shortage of BH4 which may shift in the balance between NOS-catalyzed generation of protective NO and deletorious reactive oxygen species.

Research has been conducted on nitrogenase cross-linked complex. The structural and biochemical characterization of this complex carried out to assess the mechanistic relevance of these species is described, and the results demonstrate that this chemical cross-link is formed by N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide reaction.

Introduction: Fibrin/fibrinogen degradation products (FDP) values reflect coagulation and fibrinolysis status, and FDP levels are helpful for diagnosis and classification of disseminated intravascular coagulation (DIC). FDP measurement has always played a key role in diagnosing DIC, a phenomenon that has recently gained renewed attention because of its occurrence in coronavirus disease 2019 (COVID‐19) patients. Although the evaluation of FDP is crucial for the management of critical care, the variability among FDP reagents is unclear. In this study, we aimed to compare LIASAUTO P‐FDP with three FDP reagents and investigate their characteristics. Methods: In total, 172 plasmas samples were used in the correlation. The sample data were divided into three groups including negative, no and positive discrepancy based on the discrepancy percentages calculated from each correlation between LIASAUTO P‐FDP and other three reagents. D‐dimer, plasmin‐α2 plasmin inhibitor complex (PIC), fibrin monomer complex (FMC), fibrinogen (Fbg) and Plasmin‐α2 Plasmin Inhibitor (α2PI) were measured and included in data analysis. Results: The positive discrepancy groups showed higher D‐dimer, PIC and FMC values than the negative discrepancy groups. The data indicated that LIASAUTO P‐FDP had higher reactivity to D‐dimer than other reagents and the values were elevated in the fibrinolysis‐enhanced samples with various FDP fragments. Conclusion: LIASAUTO P‐FDP displayed the reactivity towards various fibrin/fibrinogen degradation products, and it might be useful for DIC diagnosis because the fibrinolytic status differed in the DIC types and stages. [ABSTRACT FROM AUTHOR]