The evolving role of long noncoding RNA HIF1A-AS2 in diabetic retinopathy: a cross-link axis between hypoxia, oxidative stress and angiogenesis via MAPK/VEGF-dependent pathway.

BACKGROUND: Diabetic retinopathy (DR) signifies a frequent serious diabetic complication influencing retinal structure and function. Dysregulation of lncRNAs drives a wide array of human diseases especially diabetes; thus, we aimed to study lncRNA HIF1A-AS2 role and its interplay with hypoxia, oxidative stress (OS), and angiogenesis in DR. MATERIALS AND METHODS: 60 DM patients in addition to 15 healthy subjects. were enrolled. LncRNA HIF1A-AS2 mRNA relative gene expression was assessed. Hypoxia inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), mitogen activated protein kinase (MAPK), and endoglin levels were assessed. Detection of DNA damage using comet assay, and Redox status parameters were also detected. RESULTS: LncRNA HIF1A-AS2 expression was significantly increased in diabetic patients with the highest levels in proliferative DR patients. Moreover, HIFα, VEGF, MAPK, and Endogolin levels were significantly higher in the diabetic patients compared to control group with the highest levels in in proliferative DR patients. Significant DNA damage in comet assay was observed to be the highest in this group. CONCLUSION: We observed for the first time the imminent role of long noncoding RNA HIF1A-AS2 in DR throughout its stages and its interplay with hypoxia, OS, and angiogenesis via MAPK/VEGF-dependent pathway.

Fibrofast and fibrosis-4 versus fibroscan as indicators of hepatic fibrosis in non-alcoholic fatty liver disease patients: A cross sectional Study

Aims: Non-alcoholic fatty liver disease (NAFLD) is a broad category for a disease spectrum that includes simple steatosis, which can proceed to non-alcoholic steatohepatitis, cirrhosis, and, finally, hepatocellular carcinoma. Owing to the invasive nature of liver biopsy, the need for non-invasive tools were required for diagnosis. Objective: To compare the performance of simple biochemical scores (fibroblast) FIB-5 and (fibrosis-4) FIB-4 with fibroscan to differentiate mild to moderate fibrosis (MF; F0 to F2) from advanced fibrosis (AF; F3 to F4) in patients with NAFLD. Patients and methods: This cross-sectional study was done on 116 NAFLD patients. All patients were scanned with the FibroScan examination. FIB-5 and FIB-4 were calculated for all patients. Results: The mean kPa score (liver stiffness measurement score) of the patients belonging to advanced fibrosis [9.53 ± 1.05]. The FIB-4 score was significantly higher in patients with advanced fibrosis (1.54 ± 0.38) compared with patients with mild to moderate fibrosis (1.18 ± 0.44), p-value = 0.001, whereas the FIB-5 score was insignificant between patients. Conclusion: FIB-4 is superior to FIB-5 as a non-invasive simple marker in diagnosing advanced fibrosis in NAFLD patients.

Interleukin-31 interaction with inflammasome: A promising diagnostic and prognostic panel for early sepsis identification in critically ill patients.

PURPOSE: This case-control study aimed to evaluate the ability to use a panel of IL-31, IL-1ß and NLRP3 to differentiate sepsis from systemic inflammatory response syndrome (SIRS) and to predict septic shock. METHODS: Serum levels of IL-31, IL-1ß and NLRP3 were measured by ELISA in 149 participants; 38 with sepsis, 51 with SIRS, 30 with septic shock and 30 healthy controls. RESULTS: Lower levels of IL-31 were found in sepsis (10.21 ± 4.34 pg/ml) compared to SIRS (16.74 ± 3.18 pg/ml) and to controls with the lowest levels detected in septic shock (6.26 ± 2.72 pg/ml). IL-1ß and NLRP3 levels were higher in sepsis (54.99 ± 14.11 pg/ml and 9.93 ± 2.38 ng/ml) compared to SIRS (27.8 ± 6.94 pg/ml and 4.86 ± 1.33 ng/ml) with the highest levels seen in septic shock (125.1 ± 32.79 pg/ml and 19.43 ± 6.48 ng/ml) respectively. IL-31 discriminated sepsis in patients showing SIRS with 80% sensitivity and 70% specificity and, identified septic shock with 78.6% sensitivity and 60.3% specificity. IL-1ß identified sepsis from SIRS with 93.3% and 83.3% specificity. NLRP3 discriminated sepsis from SIRS with 94.5% sensitivity and 93.3% specificity. And, with sensitivity 99.1% and 90.1% and specificity 98.9% and 80% IL-1ß and NLRP3 could respectively define septic shock. A panel of combined markers provided 100% sensitivity and specificity. The three biomarkers proved to be independent prognostic biomarkers. At 95% CI, IL-31 hazard ratio (HR) was 0.716, p = 0.001; IL-1ß HR was 1.023, p ≤ 0.001; and NLRP3 HR was 1.114, p ≤ 0.001. Additionally, IL-1ß proved to be an independent predictor of septic shock (ß = 0.355; p = 0.035). CONCLUSION: The cross-relation between IL-31, IL-1ß and NLRP3 in sepsis can provide a promising diagnostic and prognostic panel.

Expression of LRP1 and CHOP genes associated with peripheral neuropathy in type 2 diabetes mellitus: Correlations with nerve conduction studies.

AIM: Diabetic peripheral neuropathy (DPN) is a frequent and debilitating complication of diabetes mellitus. The low-density lipoprotein receptor-related protein-1 (LRP-1) is a multifunctional cell surface receptor playing critical roles in lipoprotein metabolism and several cell signaling processes. C/EBP homologous protein (CHOP) is a main conduit to endoplasmic reticulum stress-induced apoptosis. We aimed to investigate LRP1 and CHOP gene expression in peripheral blood cells of type 2 diabetes mellitus (T2DM) subjects to clarify its possible relation to DPN pathogenesis. METHOD: The study included 20 non-complicated T2DM subjects, 20 subjects with DPN and 20 healthy controls. Quantitative real time PCR was used to study gene expression. RESULTS: There was a significant reduction in LRP1 mRNA expression and a significant increase in CHOP mRNA expression in subjects with DPN compared to non-complicated group and healthy controls. Both LRP1 and CHOP expression levels were inversely correlated, and both showed significant correlation with HbA1c, hyperlipidemia, hs-CRP, and different electrophysiological parameters. Receiver operating characteristics (ROC) analysis suggested that both LRP1 and CHOP mRNA expression and hs-CRP levels had great potential advantages to predict the progression of DPN. CONCLUSION: LRP1 and CHOP might be involved in DPN pathogenesis and progression, thus providing opportunities for early detection and treatment.

Nephronectin (NPNT) and the prediction of nephrotic syndrome response to steroid treatment.

Steroid-resistant nephrotic syndrome represents about 10-20% of pediatrics' nephrotic syndrome. The regeneration of glomerular barrier seems pivotal for cessation of proteinuria. Nephronectin (NPNT) plays a major role in nephrogenesis, signal transduction, and epithelial-mesenchymal interactions. This study aims to preliminary assess NPNT as potential noninvasive biomarker of glomerular regeneration and its ability to identify steroid resistance. In this case control study, 80 retrospectively selected patients with nephrotic syndrome were enrolled in addition to 40 healthy controls. Forty patients were steroid sensitive (SSNS) and the other 40 patients were steroid-resistant (SRNS), NPTN concentration was measured using ELISA and NPNT mRNA expression was assayed using real-time PCR. NPTN concentrations were significantly higher in SSNS than both SRNS and controls (The means were 4.64 ± 3.05, 0.69 ± 0.44, and 1.63 ± 0.59, respectively). Moreover, NPTN concentrations were significantly lower in SRNS than controls. NPTN was significantly overexpressed in SSNS compared to both SRNS and controls (the means were 10.82 ± 7.39, 1.19 ± 0.94, and 1.04 ± 0.10, respectively) with no statistically significant difference between SRNS and controls. ROC curves analysis showed that both NPNT expression and NPNT serum level are of promising diagnostic performance (ROCAUC 0.948 and 0.896, respectively). Regression analysis showed that both NPNT expression and NPNT serum level can be independent predictors of steroid resistance. The present study shows for the first time an enhanced expression of NPNT in steroid-sensitive nephrotic syndrome patients suggesting NPNT as a marker of glomerular regeneration. Also, serum NPNT can be a useful noninvasive biomarker of steroid resistance.

Serum FBLN1 and STK31 as biomarkers of colorectal cancer and their ability to noninvasively differentiate colorectal cancer from benign polyps.

PURPOSE: The aim of this work is to evaluate Fibulin-1 (FBLN1) and serine threonine kinase-31 (STK31) as colorectal cancer (CRC) tumour markers and their ability to differentiate it from colorectal benign lesions. MATERIAL AND METHODS: In this case-control study, FBLN1 and STK31 serum levels were measured in 120 participants; 49 CRC patients (group I), 26 patients with benign colorectal polyps (group II) and 45 healthy controls (group III). RESULTS: The means of serum FBLN1 were 1.02 ±â€¯0.95, 6.36 ±â€¯2.55 and 6.26 ±â€¯2.76 in group I, II and III respectively. Significant lower levels were found in group I compared to group II and III (both p < 0.001) with no significant difference between group II and III (p = .983). The means of serum STK31 were 13.51 ±â€¯7.67, 5.98 ±â€¯3.3 and 1.37 ±â€¯1.22 in group I, II and III respectively with significant differences in-between the 3 groups (p < 0.001). Both FBLN1 and STK31 were superior to CEA as CRC screening biomarkers; with sensitivity 90.1% and 93% respectively and specificity 93.9% and 95.9% respectively. FBLN1 differentiated CRC from benign polyps with 91.8% sensitivity and 100% specificity. STK31 differentiated CRC from benign polyps with 93.9% sensitivity and 84.6% specificity. CONCLUSION: FBLN1 and STK31 can be possible screening and differentiating biomarkers of CRC.

Circulating miR-21, miR-210 and miR-146a as potential biomarkers to differentiate acute tubular necrosis from hepatorenal syndrome in patients with liver cirrhosis: a pilot study.

BACKGROUND: Acute kidney injury (AKI) in cirrhotic patients may be functional (hepatorenal syndrome [HRS]) or structural (acute tubular necrosis [ATN]). The differentiation between these two conditions remains challenging; no definite biomarker with a clear cutoff value had been declared. miRNAs seem to be attractive innovative biomarkers to identify the nature of kidney injury in cirrhotic patients. This study aimed to investigate the possibility of using miR-21, miR-210 and miR-146a as differentiating markers between HRS and ATN. METHODS: This pilot case control study included 50 patients with liver cirrhosis; 25 with HRS and another 25 with ATN beside 30 healthy controls. Real-time qPCR was used to measure the circulating miRNA tested. RESULTS: Higher levels of miR-21 were observed in both ATN and HRS vs. controls with statistically significant difference between ATN and HRS. The means were 9.466±3.21 in ATN, 2.670±1.387 in HRS and 1.090±0.586 in controls. miR-146a and miR-210 were both significantly lower in ATN and HRS compared to controls with statistically significant differences between ATN and HRS. The means of miR-210 were 1.020±0.643, 1.640±0.605 and 3.0±0.532 in ATN, HRS and controls, respectively. The means of miR-146a were 2.543±1.929, 4.98±1.353 and 6.553±0.426 in ATN, HRS and controls, respectively. ROC analyses proved that the three studied mi-RNAs can be used as differentiating biomarkers between ATN and HRS with the best performance observed with mi-21 achieving specificity and sensitivity equal 96%. CONCLUSIONS: miR-21, miR-210 and miR-146a may be candidate differentiating markers between HRS and ATN in cirrhotic patients.