Mycobacterium marinum mediates regulation of prostaglandin E2 expression on host immune response through cyclooxygenase pathway.

PURPOSE: Investigate the role of COX signaling in activating the PGE2-EP2 pathway. METHODS: Utilized a marine Mycobacterium infection model in zebrafish. Marine mycobacteria were stained with fluorescein isothiocyanate. The COX inhibitor indomethacin, EP2 receptor inhibitor AH6809, EP4 receptor inhibitor AH23848 and clodronate Liposomes were used to investigate the role of COX, EP2, EP4 and macrophage whether participating in combat marine mycobacterial infection. The expression level of the target gene was detected using real-time fluorescence quantitative PCR instrument. RESULTS: The findings revealed that larvae exposed to the COX inhibitor indomethacin or the EP2 receptor inhibitor AH6809 demonstrated a significantly higher mortality rate due to marine mycobacterium infection than those in the control group. Administration of exogenous prostaglandin E2 (PGE2) rescued the survival of zebrafish infected with marine mycobacteria and treated with indomethacin. Additionally, a significant reduction in survival rate was noted in macrophage-depleted zebrafish infected with marine mycobacteria. CONCLUSION: The host may combat marine mycobacterium infection via COX signaling, which activates the PGE2-EP2 pathway and mediates macrophage resistance.

Mechanisms of circular RNA degradation.

Circular RNAs (CircRNAs) are a class of noncoding RNAs formed by backsplicing during cotranscriptional and posttranscriptional processes, and they widely exist in various organisms. CircRNAs have multiple biological functions and are associated with the occurrence and development of many diseases. While the biogenesis and biological function of circRNAs have been extensively studied, there are few studies on circRNA degradation and only a few pathways for specific circRNA degradation have been identified. Here we outline basic information about circRNAs, summarize the research on the circRNA degradation mechanisms and discusses where this field might head, hoping to provide some inspiration and guidance for scholars who aim to study the degradation of circRNAs.

An analysis of the role of HnRNP C dysregulation in cancers.

Heterogeneous nuclear ribonucleoproteins C (HnRNP C) is part of the hnRNP family of RNA-binding proteins. The relationship between hnRNP C and cancers has been extensively studied, and dysregulation of hnRNP C has been found in many cancers. According to existing public data, hnRNP C could promote the maturation of new heterogeneous nuclear RNAs (hnRNA s, also referred to as pre-mRNAs) into mRNAs and could stabilize mRNAs, controlling their translation. This paper reviews the regulation and dysregulation of hnRNP C in cancers. It interacts with some cancer genes and other biological molecules, such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and double-stranded RNAs (dsRNAs). Even directly binds to them. The effects of hnRNP C on biological processes such as alternative cleavage and polyadenylation (APA) and N6-methyladenosine (m6A) modification differ among cancers. Its main function is regulating stability and level of translation of cancer genes, and the hnRNP C is regarded as a candidate biomarker and might be valuable for prognosis evaluation.

Prevalence and Prognosis of HFimpEF Developed From Patients With Heart Failure With Reduced Ejection Fraction: Systematic Review and Meta-Analysis.

Background: Heart failure with improved ejection fraction (HFimpEF) is classified as a new type of heart failure, and its prevalence and prognosis are not consistent in previous studies. There is no systematic review and meta-analysis regarding the prevalence and prognosis of the HFimpEF. Method: A systematic search was performed in MEDLINE, EMBASE, and Cochrane Library from inception to May 22, 2021 (PROSPERO registration: CRD42021260422). Studies were included for analysis if the prognosis of mortality or hospitalization were reported in HFimpEF or in patients with heart failure with recovered ejection fraction (HFrecEF). The primary outcome was all-cause mortality. Cardiac hospitalization, all-cause hospitalization, and composite events of mortality and hospitalization were considered as secondary outcomes. Result: Nine studies consisting of 9,491 heart failure patients were eventually included. During an average follow-up of 3.8 years, the pooled prevalence of HFimpEF was 22.64%. HFimpEF had a lower risk of mortality compared with heart failure patients with reduced ejection fraction (HFrEF) (adjusted HR: 0.44, 95% CI: 0.33-0.60). HFimpEF was also associated with a lower risk of cardiac hospitalization (HR: 0.40, 95% CI: 0.20-0.82) and the composite endpoint of mortality and hospitalization (HR: 0.56, 95% CI: 0.44-0.73). Compared with patients with preserved ejection fraction (HFpEF), HFimpEF was associated with a moderately lower risk of mortality (HR: 0.42, 95% CI: 0.32-0.55) and hospitalization (HR: 0.73, 95% CI: 0.58-0.92). Conclusion: Around 22.64% of patients with HFrEF would be treated to become HFimpEF, who would then obtain a 56% decrease in mortality risk. Meanwhile, HFimpEF is associated with lower heart failure hospitalization. Further studies are required to explore how to promote left ventricular ejection fraction improvement and improve the prognosis of persistent HFrEF in patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021260422, identifier: CRD42021260422.

Feasibility of coding-based Charlson comorbidity index for hospitalized patients in China, a representative developing country.

BACKGROUND: The Charlson Comorbidity Index (CCI) can be automatically calculated from the International Classification of Disease (ICD) code. However, the feasibility of this transformation has not been acknowledged, particularly in hospitals without a qualified ICD coding system. Here, we investigated the utility of coding-based CCI in China. METHODS: A multi-center, population-based, retrospective observational study was conducted, using a dataset incorporating 2,464,395 adult subjects from 15 hospitals. CCI was calculated using both ICD-10-based and diagnosis-based method, according to the transformation rule reported previously and to the literal description from discharge diagnosis, respectively. A κ coefficient of variation was used as a measure of agreement between the above two methods for each hospital. The discriminative abilities of the two methods were compared using the receiver-of-operating characteristic curve (ROC) for prediction of in-hospital mortality. RESULTS: Total agreement between the ICD-based and diagnosis-based CCI for each index ranged from 86.1 to 100%, with κ coefficients from 0.210 [95% confidence interval (CI) 0.208-0.212] to 0.932 (95% CI 0.924-0.940). None of the 19 indices of CCI had a κ coefficient > 0.75 in all the hospitals included for study. The area under the curve of ROC for in-hospital mortality of all 15 hospitals was significantly lower for ICD-based than diagnosis-based CCI [0.735 (0.732, 0.739) vs 0.760 (0.757, 0.764)], indicative of more limited discriminative ability of the ICD-based calculation. CONCLUSIONS: CCI calculated using ICD-10 coding did not agree with diagnosis-based CCI. ICD-based CCI displayed diminished discrimination performance in terms of in-hospital mortality, indicating that this method is not promising for CCI scoring in China under the present circumstances.

Soluble Urokinase Plasminogen Activator Receptor is Associated with Coronary Artery Calcification and Cardiovascular Disease in Patients Undergoing Hemodialysis.

BACKGROUND/AIMS: Cardiovascular disease (CVD) is an important cause of morbidity and mortality in hemodialysis patients. Vascular calcification is thought to play an important role in causing CVD. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker strongly predictive of cardiovascular outcomes in the pathogenesis of diabetic patients with renal disease treated with hemodialysis. We investigated the relationship between suPAR and coronary artery calcification (CAC) in patients undergoing maintenance hemodialysis. METHODS: A total of 99 adult hemodialysis patients were enrolled in this study. Plasma samples were analyzed for suPAR with an enzyme-linked immunosorbent assay and the CAC score was determined with multidetector computed tomography. The occurrence of cardiovascular events and all-cause mortality during follow-up were recorded from January 1, 2010 to June 1, 2016. RESULTS: In 99 patients treated with maintenance hemodialysis, 91 (91.9%) had varying degrees of CAC, and suPAR correlated positively with the CAC score in a Spearman analysis. In a mean follow-up period of 33 months, 36 patients (36.4%) experienced at least one cardiovascular event. When the quartiles of suPAR concentrations were used as the cutoff points for a subgroup analysis, the incidence of CVD and all-cause mortality was much higher in the higher quartiles of suPAR. In a univariate Cox regression analysis, high suPAR was a risk factor for CVD and all-cause mortality. CONCLUSION: suPAR is associated with the CAC score and is a risk factor for new-onset CVD in patients undergoing hemodialysis.

Red blood cell distribution width as a marker of cerebral infarction in hemodialysis patients.

BACKGROUND: Red blood cell distribution width (RDW) is a cardiovascular biomarker. We evaluated the association between RDW and cerebral stroke risk in hemodialysis patients. METHODS: A cohort of 442 adult patients on hemodialysis was studied. Strokes were defined according to ICD-10 diagnosis codes. Routine complete blood counts, evaluated every 3-6 months, were used for RDW values. RESULTS: Among 442 hemodialysis patients, during the 50-month follow-up, there were 62 cases (14.0%) of cerebral stroke: 41 (9.3%) with cerebral infarction and 21 (4.8%) with cerebral hemorrhage. Compared with nonstroke patients, a significantly higher RDW was measured in patients with cerebral stroke and cerebral infarction. However, no significant difference was seen in RDW between patients with cerebral hemorrhage and nonstroke patients. After adjustment by age, hypertension, albumin, Charlson Comorbidity Score, and C-reactive protein in different multivariable Cox regression models, patients with the highest mean RDW quartile had a 2.55-fold (hazard ratio = 3.55; 95% confidence interval: 1.33-9.51) higher risk of developing cerebral infarction relative to those with the lowest mean RDW quartile. RDW was not an independent risk factor for cerebral hemorrhage. CONCLUSIONS: Increased RDW is an independent risk factor of cerebral infarction in hemodialysis patients.

Peripheral kynurenine/tryptophan ratio is not a reliable marker of systemic indoleamine 2,3-dioxygenase: A lesson drawn from patients on hemodialysis.

Indoleamine 2,3-dioxygenase (IDO) has emerged as a pivotal enzyme for mediating immune tolerance. Because IDO metabolizes tryptophan into kynurenine, the plasma kynurenine/tryptophan (Kyn/Trp) ratio has been widely used as a marker of systemic IDO. Here, we evaluated the clinical value of using the plasma Kyn/Trp ratio to estimate cell-mediated immune responses to tuberculin skin testing and risk of new bacterial infection. We also compared the Kyn/Trp ratio to a novel IDO marker, the IDO median fluorescence index (MFI) of peripheral blood mononuclear cells, which was determined by flow cytometry. In 228 patients from two hemodialysis centers, the two IDO markers were higher in patients than in healthy controls but were not correlated with each other. In vitro experiments demonstrated that peripheral blood mononuclear cells could not metabolize tryptophan into kynurenine, indicating that the increased Kyn/Trp ratio was IDO-independent. Skin induration diameters of tuberculin skin testing were correlated with the IDO MFI (negatively), but not the Kyn/Trp ratio. Further, in a 24-month prospective cohort, the Kyn/Trp ratio was not correlated with clinical infection. Alternatively, patients with a higher IDO MFI had a lower accumulative infection-free survival rate. Using a Cox proportional hazard model, it was also revealed that a higher IDO MFI was significantly associated with new bacterial infection. Taken together, these results indicate that the Kyn/Trp ratio is not a reliable circulating IDO marker in hemodialysis patients. However, the IDO MFI reflects an immunocompromised state and thus might be a potential clinical marker of bacterial infection.

Proteinuria as an independent risk factor for contrast-induced acute kidney injury and mortality in patients with stroke undergoing cerebral angiography.

BACKGROUND: The correlation between proteinuria and contrast-induced acute kidney injury (CI-AKI) in patients with cerebrovascular disease is still unknown. OBJECTIVE: To determine whether proteinuria is a risk factor for CI-AKI and death in patients with stroke undergoing cerebral angiography. METHODS: Data from 2015 patients with stroke undergoing cerebral angiography between January 2009 and December 2013 were retrospectively collected. Clinical parameters were obtained from the hospital's computerized database. All variables were analyzed by univariate analysis and multivariate logistic regression analysis. RESULTS: CI-AKI was seen in 85 patients (4.2%). After adjustment for potential confounding risk factors, patients with proteinuria had a fivefold higher risk of CI-AKI than patients without proteinuria (OR=5.74; 95% CI 2.23 to 14.83; p<0.001). Other independent risk factors for CI-AKI were estimated glomerular filtration rate <60 mL/min/1.73 m2, anemia, and a high National Institute of Health Stroke Scale score. Proteinuria did not increase in-hospital mortality (OR=1.25; 95% CI 0.49 to 3.17; p=0.639) but did increase 1-year mortality (HR=2.30, 95% CI 1.55 to 3.41, p<0.001). CONCLUSIONS: Proteinuria is an independent risk factor for CI-AKI and 1-year mortality in patients with stroke undergoing cerebral angiography. More attention should be paid to the development of CI-AKI in patients with stroke with proteinuria.