Construction and Investigation of an LINC00284-Associated Regulatory Network in Serous Ovarian CarcinomaRead the full article
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CD26-Related Serum Biomarkers: sCD26 Protein, DPP4 Activity, and Anti-CD26 Isotype Levels in a Colorectal Cancer-Screening Context
Current screening trials are showing reduction in colorectal cancer incidence and mortality. However, participation rates are often low, and blood-based tests could complement existing screening strategies. CD26 protein (sCD26) and its dipeptidyl peptidase IV (DPP4) enzymatic activity in circulation have been proposed as biomarkers for colorectal cancer and other diseases. However, changes in sCD26 and DPP4 levels show complex degrees of correlation, and their physiological or pathophysiological role is unclear. The aim of this study was to analyse if anti-CD26 autoantibodies are related to sCD26 and DPP4 and to determine their relevance in a context of colorectal cancer screening for complementing the value of sCD26 and DPP4 as biomarkers. These biomarkers were measured in a large prospective cohort (, except the anti-CD26 antibodies, evaluated in 125 samples) that included a subgroup of individuals that were positive for the faecal immunological occult blood test (FIT) () and underwent a colonoscopy (). We confirmed for the first time higher DPP4 activity in men compared to women (Student’s test, ), though this difference between sexes was not seen for serum sCD26 protein. These biomarkers correlated (, ) only in women. Correlations were found between anti-CD26 isotypes but not with DPP4 activity or sCD26 concentration, except for a negative correlation only in men between anti-CD26 IgA isotype and sCD26 (, ), and an almost significant negative correlation between anti-CD26 IgG and sCD26 limited to FIT-positive men. Interestingly, patients with advanced adenomas displayed the most elevated mean levels of anti-CD26 IgA, IgM, and particularly IgG (Mann-Whitney test, ) in comparison with the other FIT positives without adenomas, and these levels did not correlate with sCD26 or its DPP4 activity. Our preliminary results suggest that the combination of these measures using sex as confounder could perhaps be used as biomarkers for colorectal disease. It also suggests that events affecting the gut influence the levels of anti-CD26 antibodies, which show little or no effect in antigen clearance. These findings should be confirmed in a larger cohort of individuals with colonoscopy. The physiological origin of the sex differences observed should be further addressed.
New Insights into the Role of Tyro3, Axl, and Mer Receptors in Rheumatoid Arthritis
Rheumatoid Arthritis (RA) is the most common chronic inflammatory autoimmune disease involving joints. Among several pathogenic mechanisms, the impairment of homeostatic regulators of inflammation seems to be critically important to sustain persistent infiltration and activation of immune and stromal cells within the diseased synovium. Tyrosine kinase receptors Tyro3, Axl, and Mer are members of the TAM family. Upon binding their ligands Growth Arrest-Specific gene 6 (Gas6) and Protein S (ProS1), TAM receptors (TAMs) exert numerous and diverse biologic functions. Activated Axl and Mer, for instance, can negatively regulate the inflammatory cascade and mediate phagocytosis of apoptotic cells, contributing to prevent the development of autoimmunity. Thus, a role for TAMs has been hypothesized in RA. In this review, we will summarise unmet clinical needs in RA, depict the biology of TAMs and TAM ligands, focussing on their ability to regulate the immune system and inflammation cascade, and finally offer an overview of the state-of-the-art literature about the putative role of TAM axis in RA.
A Meta-Analysis of Robotic Surgery in Endometrial Cancer: Comparison with Laparoscopy and Laparotomy
Background. The safety and effectiveness of robotic surgery are evaluated by comparing perioperative outcomes with laparoscopy and laparotomy in endometrial cancer. Method. PubMed, MEDLINE, Embase, Cochrane, and other databases were searched for eligible studies up to April 2019. Studies that compared robotic surgery with laparoscopy or laparotomy in surgical staging of endometrial cancer were included. The pooled odds ratio and weighted mean difference were calculated using a random-effects or a fixed-effects model to summarize the results. Results. Twenty-seven articles were ultimately included, with one randomized controlled trial and 26 observational studies. A total of 6568 patients were included. Meta-analysis showed that robotic surgery had less estimated blood loss (), blood transfusion (), intraoperative complications (), and conversion to open surgery (), and a shorter hospital stay (), but had a longer operation time () in surgical staging of endometrial cancer compared with laparoscopy. There were no significant differences in postoperative complications, the total number of lymph nodes harvested, the number of pelvic lymph nodes harvested, and the number of para-aortic lymph nodes harvested between techniques. Robotic surgery had a longer operation time (), less estimated blood loss (), blood transfusion (), and postoperative complications (), and a shorter hospital stay () compared with laparotomy. There were no significant differences in other variables between techniques. Conclusion. Robotic surgery is a safer surgical approach than laparoscopy and laparotomy in surgical staging of endometrial cancer, with less estimated blood loss, blood transfusion, and conversion, and the same number of lymph nodes harvested.
Serum Anion Gap Predicts All-Cause Mortality in Critically Ill Patients with Acute Kidney Injury: Analysis of the MIMIC-III Database
Background. No epidemiological study has investigated the effect of anion gap (AG) on the prognosis of critically ill patients with acute kidney injury (AKI). Therefore, we aimed to determine the association between serum AG and all-cause mortality in these patients. Methods. From MIMIC III, we extracted demographics, vital signs, laboratory tests, comorbidities, and scoring systems from the first 24 h after patient ICU admission. A generalized additive model was used to identify a nonlinear association between anion gap and 30-day all-cause mortality. We also used the Cox proportional hazards models to measure the association between AG levels and 30-day, 90-day, and 365-day mortality in patients with AKI. Results. A total of 11,573 eligible subjects were extracted from the MIMIC-III. The relationship between AG levels and 30-day all-cause mortality in patients with AKI was nonlinear, with a U-shaped curve. In multivariate analysis, after adjusting for potential confounders, higher AG was a significant predictor of 30-day, 90-day, and 365-day all-cause mortality compared with lower AG (HR, 95% CI: 1.54, 1.33–1.75; 1.55, 1.38–1.73; 1.46, 1.31–1.60). Conclusions. The relationship between AG levels and 30-day all-cause mortality described a U-shaped curve. High-AG levels were associated with increased risk 30-day, 90-day, and 365-day all-cause mortality in critically ill patients with AKI.
Long Noncoding RNA AFAP1-AS1 Promotes Cell Proliferation and Metastasis via the miR-155-5p/FGF7 Axis and Predicts Poor Prognosis in Gastric Cancer
Background. Actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) plays an important role in the development and progression of several human cancers. However, its biological function in gastric cancer (GC) progression is still unknown. Methods. We used qRT-PCR to detect the relative expression of AFAP1-AS1 in GC tissues and cell lines. The loss-of-function assays were conducted to detect the effect of AFAP1-AS1 on GC development. Bioinformatics analysis, luciferase reporter gene analysis, and RIP analysis were used to identify and validate target genes of AFAP1-AS1. Finally, rescue tests were performed to confirm the influence of the AFAP1-AS1-miR-155-5p-FGF7 axis on GC development. Results. AFAP1-AS1 was upregulated in GC tissues and cell lines and was closely correlated with poor prognosis of GC patients. AFAP1-AS1 knockdown inhibited proliferation, migration, and invasion of GC cells, indicating that AFAP1-AS1 acts as an oncogene in GC. Bioinformatics analysis, dual-luciferase reporter gene detection, and RIP assays validated that AFAP1-AS1 directly interacts to miR-155-5p and could positively affect cell proliferation, migration, and invasion by regulation of the expression of miR-155-5p and FGF7. Further rescue assays revealed that AFAP1-AS1 promotes cell proliferation and metastasis through the miR-155-5p/FGF7 axis in GC. Conclusions. AFAP1-AS1 might be an oncogenic lncRNA that promoted GC progression by acting as a competing endogenous RNA (ceRNA) that regulates the expression of FGF7 through sponging miR-155-5p, suggesting that AFAP1-AS1 may be a novel potential therapeutic target for GC.
Plasma Adipokines in Patients Resuscitated from Cardiac Arrest: Difference of Visfatin between Survivors and Nonsurvivors
Background. Adipokines are a group of cytokines or peptides secreted by adipose tissue to exert numerous biological functions. In the present study, we measured the plasma levels of four adipokines (adiponectin, leptin, fatty acid-binding protein 4 (FABP4), and visfatin) in cardiac arrest patients following return of spontaneous circulation (ROSC). Methods. Totally, 21 patients who experienced cardiac arrest and successful ROSC with expected survival of at least 48 hours (from January 2016 to December 2017) were consecutively enrolled into this prospective observational clinical study. Of the 21 enrolled patients, ten survived, and other eleven died between 2 days and 6 months post ROSC. Venous blood was drawn at three time points: baseline (<1 hour post ROSC), 2 days post ROSC, and 7 days post ROSC. Plasma concentrations of adiponectin, leptin, FABP4, and visfatin were determined using commercial enzyme-linked immunosorbent assays. Results. The plasma visfatin levels at 2 or 7 days post ROSC increased significantly compared with the baseline (), while plasma levels of adiponectin, leptin, and FABP4 did not change. Moreover, plasma visfatin levels in survivors at 2 or 7 days post ROSC were higher than those in nonsurvivors (). Plasma visfatin levels at 2 or 7 days post ROSC were negatively correlated with Acute Physiology and Chronic Health Evaluation (APACHE) II score and time to ROSC. Moreover, receiver operating characteristic curve analysis showed that the plasma visfatin levels at 2 or 7 days post ROSC were good predictors for survival of the patients. Conclusion. Elevated plasma visfatin levels may be a marker for better outcome of cardiac arrest patients post ROSC.