Analysis of the Correlation of Galectin-3 Concentration with the Measurements of Echocardiographic Parameters Assessing Left Atrial Remodeling and Function in Patients with Persistent Atrial Fibrillation

Galectin-3 (gal-3) is a fibrosis marker and may play a role in fibrosis of the left atrium (LA). Left atrial wall fibrosis may influence the transition from paroxysmal to non-paroxysmal atrial fibrillation (AF). In this study, we assessed the correlation of gal-3 concentration with the main echocardio-graphic parameters evaluating dimensions, volume, compliance, and left atrial contractility during AF and after successful electrical cardioversion (DCCV). The study included 63 patients with left atrial enlargement who qualified for DCCV due to persistent AF. The procedure recovered sinus rhythm in 43 (68.3%) patients. The concentration of gal-3 was negatively correlated with the echocardiographic parameters of LA including dimensions (LA length pre, rho = −0.38; p = 0.003), volume (LAV pre, rho = −0.39; p = 0.003), compliance (LASr mean post, rho = −0.33) and contractility (pLASRct mean post, rho = −0.33; p = 0.038). Negative correlations of gal-3 concentration were also observed in relation to the volume and contractility of the left ventricle. The concentration of gal-3 significantly negatively correlates with the size, systolic function, and compliance of the LA wall in patients with persistent AF. Determining gal-3 concentration in patients with persistent AF may help in the assessment of remodeling of the LA wall.

A Novel OGR1 (GPR68) Inhibitor Attenuates Inflammation in Murine Models of Colitis

<b><i>Background and Aims:</i></b> Local extracellular acidification is associated with several conditions, such as ischemia, cancer, metabolic disease, respiratory diseases, and inflammatory bowel disease (IBD). Several recent studies reported a link between IBD and a family of pH-sensing G protein-coupled receptors. Our previous studies point to an essential role for OGR1 (GPR68) in the modulation of intestinal inflammation and fibrosis. In the current study, we evaluated the effects of a novel OGR1 inhibitor in murine models of colitis. <b><i>Methods:</i></b> The effects of a novel small-molecule OGR1 inhibitor were assessed in the acute and chronic dextran sulfate sodium (DSS) murine models of colitis. Macroscopic disease indicators of intestinal inflammation were evaluated, and epithelial damage and immune cell infiltration and proliferation were assessed by immunohistochemistry. <b><i>Results:</i></b> The OGR1 inhibitor ameliorated clinical parameters in acute and chronic DSS-induced colitis. In mice treated with the OGR1 inhibitor, endoscopy showed no thickening and normal vascularity, while fibrin was not detected. Histopathological findings revealed a decrease in severity of colonic inflammation in the OGR1 inhibitor group when compared to vehicle-DSS controls. In OGR1 inhibitor-treated mice, staining for the macrophage marker F4/80 and cellular proliferation marker Ki-67 revealed a reduction of infiltrating macrophages and slightly enhanced cell proliferation, respectively. This was accompanied by a reduction in pro-inflammatory cytokines, TNF and IL-6, and the fibrosis marker TGF-β1. <b><i>Conclusion:</i></b> This is the first report providing evidence that a pharmacological inhibition of OGR1 has a therapeutic effect in murine colitis models. Our data suggest that targeting proton-sensing OGR1 using specific small-molecule inhibitors may be a novel therapeutic approach for the treatment of IBD.

Preoperative Fibrosis-4 (FIB-4) Evaluation May Be Helpful to Evaluate Prognosis of Gastric Cancer Patients Undergoing Operation: A Retrospective Study

BackgroundLiver dysfunction and chronic inflammation influence the prognosis of many tumors and surgical outcomes. This study was performed to determine whether the Fibrosis-4 (FIB-4) index, originally defined as a noninvasive fibrosis marker, can predict the prognosis of patients with gastric cancer undergoing radical gastric cancer surgery.MethodsWe have retrospectively analyzed 594 consecutive patients with gastric cancer who underwent gastrectomy in our database. The FIB-4 index was calculated using laboratory data and age before gastrectomy. The clinical utility of FIB-4 was evaluated by X-tile. Patients were divided into two groups (high and low FIB-4 index groups), and their overall survival (OS) was investigated. Cox regression analysis was used to identify the independent parameters associated with prognosis. Finally, we developed a prognostic prediction model by using R statistical software.ResultsA total of 556 patients, including 422 men and 134 women, were enrolled. Of these, 61 (11.0%) and 495 (89.0%) patients had low and FIB-4 indexes, respectively. In addition to the indicators of FIB-4, preoperative age, tumor site, surgical procedure, TNM stage, and postoperative complications were found to be independent predictors of prognosis (P &lt; 0.05). Among patients, the FIB-4 index group had significantly shorter OS (log-rank P = 0.01) than the low FIB-4 index group. This association was also confirmed in the multivariate analysis (hazard ratio, 4.65; 95% confidence interval, 1.07-4.29; P = 0.031).ConclusionsPreoperative FIB-4 index can predict long-term outcomes of gastric cancer patients who had undergone gastrectomy.

MiR-214 promotes renal fibrosis in diabetic nephropathy via targeting SOCS1

Purpose: To elucidate how miR-214 regulates the pathogenesis of diabetic nephropathy (DN). Methods: The extent of fibrosis in DN mice kidneys was examined using Masson’s staining. Quantitative polymerase chain reaction (qPCR) was used to determine the levels of miR-214. Dual luciferase reporter assay was used to identify the target of miR-214. The expression of fibrosis marker proteins of high glucose-stimulated NRK-52E cells transfected with miR-214 was determined using western blotting. Results: Fibrosis in renal tissue of DN mice was significantly increased and miR-214 was upregulated (p < 0.001). Suppressor of cytokine signaling 1 protein (SOCS1) was the target gene of miR-214, and overexpression of miR-214 promoted fibrosis (p < 0.05, p < 0.001). On the other hand, overexpression of SOCS1 inhibited this process, indicating that miR-214 promoted fibrosis via targeting SOCS1 (p < 0.001). Finally, inhibition of miR-214 c ameliorated renal fibrosis in DN mice (p < 0.01, p < 0.001). Conclusions: MiR-214 is upregulated in db/db DN mice kidney tissue; miR-214 regulates renal fibrosis in DN mice by targeting SOCS1.

Less liver fibrosis marker increment in overweight chronic hepatitis B patients observed by age-adjusted Fibrosis-4 Index

Background and aimsChronic hepatitis B patients in Taiwan with no or limited liver injury are not reimbursed for antiviral treatment by the Taiwan National Health Insurance (NHI). Innovative fibrosis marker, age-adjusted Fibrosis-4 Index (FIB4-AA), was implemented to evaluate the tendency of liver fibrosis in these patients.MethodsThe FIB-4 indices of 256 antiviral treatment-naïve chronic hepatitis B patients at Kaohsiung Medical University Hospital from 2003 to 2019 were reviewed. The difference in initial FIB-4 and last FIB4-AA was treated as a categorical variable, representing the tendency of liver fibrosis in each individual aside from ageing. Logistic regression was implemented to evaluate the three parameters most dependent on increment of FIB4-AA: e seroconversion, body mass index (BMI) and initial FIB-4 index.ResultsThe yearly FIB-4 growth rate of an individual without chronic hepatitis was lower than that of the study group (0.0237 vs 0.0273 for males, 0.02 vs 0.0288 for females). Patients undergoing or completing e seroconversion were less prone to increment of FIB4-AA (p=0.036, OR 0.524). Logistic regression revealed that BMI ≥25 kg/m2 significantly less increment of FIB4-AA (p=0.001, OR 0.383, 95% CI 0.212 to 0.690), while patients with initial FIB-4 <1.29 were prone to increasing liver FIB4-AA (p=0.000, OR 3.687, 95% CI 1.999 to 6.797).ConclusionChronic hepatitis B patients not meeting the reimbursement criteria of the Taiwan NHI are prone to increment of liver fibrosis marker. Overweight is associated with less increment of fibrosis marker, while initial FIB-4 <1.29 is associated with increasing fibrosis marker.

Abstract 12989: Long-term Prognostic Value of Fibrosis-4 Index and Albumin-bilirubin Score in Patients Admitted for Acute Decompensated Heart Failure

Backgrounds: Cardiohepatic interactions have been a focus of attention among heart failure (HF). It was reported that liver stiffness assessed by non-invasive fibrosis marker such as Fibrosis-4(FIB4) index provide prognostic information in HF patients. Furthermore, the albumin-bilirubin (ALBI) score has recently been proposed as a validated index of liver dysfunction. We sought to investigate the long-term prognostic values of the combination of FIB4 index and ALBI score in patients admitted for acute decompensated heart failure (ADHF). Methods and Results: We studied 299 ADHF pts with survival discharge. FIB4 index was calculated by the formula: age(yrs) х AST[U/L]/(platelets [10 3 /μL] х (ALT[U/L]) 1/2 ). The ALBI was calculated using the formula: log 10 (total bilirubin) х 0.66 + albuminх-0.085. During a follow-up period of 4.3±3.3 yrs, 94 patients died. At multivariate Cox analysis, FIB4 index and ALBI score were significantly associated with total mortality, independently of prior HF hospitalization and body mass index after adjustment with systolic blood pressure, left ventricular end-diastolic dimension and left atrial dimension indexes. Patients with both greater FIB4 index (>3.608: top tertile) and ALBI score (>-2.076:top tertile) had a significantly higher risk of total mortality than those with either or none of them (46% vs 34% vs 25%, respectively, p=0.002). Conclusion: The combination of FIB4 index and ALBI score might identify higher risk subset for total mortality in ADHF patients.