Diagnostic Significance of hsa-miR-21-5p, hsa-miR-192-5p, hsa-miR-155-5p, hsa-miR-199a-5p Panel and Ratios in Hepatocellular Carcinoma on Top of Liver Cirrhosis in HCV-Infected Patients.

Early hepatocellular carcinoma (HCC) diagnosis is challenging. Moreover, for patients with alpha-fetoprotein (AFP)-negative HCC, this challenge is augmented. MicroRNAs (miRs) profiles may serve as potential HCC molecular markers. We aimed to assess plasma homo sapiens-(hsa)-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p-expression levels as a panel of biomarkers for HCC in chronic hepatitis C virus (CHCV) patients with liver cirrhosis (LC), especially AFP-negative HCC cases, as a step toward non-protein coding (nc) RNA precision medicine. SUBJECTS AND METHODS: 79 patients enrolled with CHCV infection with LC, subclassified into an LC group without HCC (n = 40) and LC with HCC (n = 39). Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p. RESULTS: Plasma hsa-miR-21-5p and hsa-miR-155-5p demonstrated significant upregulation, while hsa-miR-199a-5p demonstrated significant downregulation in the HCC group (n = 39) when compared to the LC group (n = 40). hsa-miR-21-5p expression was positively correlated with serum AFP, insulin, and insulin resistance (r = 0.5, p < 0.001, r = 0.334, p = 0.01, and r = 0.303, p = 0.02, respectively). According to the ROC curves, for differentiating HCC from LC, combining AFP with each of hsa-miR-21-5p, hsa-miR-155-5p, and miR199a-5p improved the diagnostic sensitivity to 87%, 82%, and 84%, respectively, vs. 69% for AFP alone, with acceptable specificities of 77.5%, 77.5%, and 80%, respectively, and AUC = 0.89, 0.85, and 0.90, respectively vs. 0.85 for AFP alone. hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios discriminated HCC from LC at AUC = 0.76 and 0.71, respectively, with sensitivities = 94% and 92% and specificities = 48% and 53%, respectively. Upregulation of plasma hsa-miR-21-5p was considered as an independent risk factor for HCC development [OR = 1.198(1.063-1.329), p = 0.002]. CONCLUSIONS: Combining each of hsa-miR-21-5p, hsa-miR-155-5p, and hsa-miR-199a-5p with AFP made it possible to identify HCC development in the LC patients' cohort with higher sensitivity than using AFP alone. hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios are potential HCC molecular markers for AFP-negative HCC patients. hsa-miR-21-5p was linked, clinically and via in silico proof, to insulin metabolism, inflammation, dyslipidemia, and tumorigenesis in the HCC patients' group as well as for an upregulated independent risk factor for the emergence of HCC from LC in the CHCV patients.

Serum Collagen Triple Helix Repeat Containing-1 Levels are Related to Radiological Affection and Disease Activity in Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a common systemic inflammatory disease. Collagen triple helix repeat containing-1 (CTHRC1) is a unique gene product able to reduce collagen deposition. The present study aimed to assess CTHRC1 level in RA patients and to uncover its relation to clinical, laboratory and radiological findings. Methods: The study included 60 adult RA patients. In addition, there were 60 control subjects who included patients with osteoarthritis (n = 20) and reactive arthritis (n = 20) and healthy controls (n = 20). Serum CTHRC1 levels were assessed by Enzyme-Linked Immunosorbent Assay (ELISA). Disease activity was calculated using the Disease Activity Score (DAS28-CRP). Radiological damage was evaluated using the Simple Erosion Narrowing Score (SENS). Results: There was significantly higher serum CTHRC1 levels in RA patients when compared to OA, ReA and control groups [median (IQR): 4.66 (1.68-11.7) versus 1.88 (1.14-2.94), 1.55 (0.98-3.15) and 1.14 (0.85-1.3) mg/dL, respectively, p < 0.001]. There was significantly higher CTHRC1 levels in patients with higher disease activity [median (IQR): 2.23 (1.4-4.73) versus 6.55 (4.66-12.0) mg/dL, p = 0.004]. Patients with higher SENS had significantly higher CTHRC1 [median (IQR): 1.99 (1.4-4.66) versus 9.75 (4.39-12.63) mg/dL, p < 0.001] and DAS28 [median (IQR): 4.25 (2.9-5.2) versus 5.4 (4.65-5.8), p = 0.01]. Conclusion: Serum CTHRC1 levels are related to disease severity and radiological affection in RA patients.

Utility of Adipokines and IL-10 in Association with Anthropometry in Prediction of Insulin Resistance in Obese Children.

Aim: This is a case-controlled study, with two hundred children enrolled. They were divided into an obese group of 100 children who had BMI ≥ 95th percentile according to CDC criteria and a group of 100 children with normal weight. All enrolled children were subjected to detailed medical history and clinical examination, in addition to measuring fasting blood sugar, fasting serum insulin, HOMA-IR calculation, lipid profile analysis, total serum cholesterol, low- and high-density lipoproteins (LDL and HDL), and serum triglyceride (TG). Two adipokines (lipocalin-2 and adipsin) serum levels plus IL-10 serum level were assessed. Results: Higher Z score of weight, MI, and waist/height ratio and high serum cholesterol, LDL, TG, and low HDL were observed in obese children. Higher levels of serum lipocalin-2 and adipsin and lower IL-10 blood level were observed in the obese group in comparison with the normal weight children. Higher insulin resistance index was observed in the obese group, with positive correlation of HOMA-IR with the anthropometric measurements and lipocalin serum level, while negative correlation was observed between IL-10 and fasting insulin in obese children. Conclusion: Simple measurement of general and central adiposity markers and serum lipocalin-2 can predict insulin resistance in obese children while serum adipsin and IL-10 had no association with insulin resistance.

Assessment of coagulation markers, serum zinc and copper in children with beta-thalassemia major in Egypt.

BACKGROUND: Thalassemia is one of the commonest single gene disorders usually associated with many complications. Coagulation changes as well as trace elements levels alterations have been described in children with ß thalassemia. Activation of coagulation can be assessed by measuring thrombin-antithrombin (TAT) complex, plasmin-antiplasmin (PAP) complex and ß-thromboglobulin (ß-TG). METHODS: A total of 200 children and adolescents were enrolled in the study; 100 were from the Al-Azhar University hospital's pediatric hematology clinic diagnosed as thalassemia major, while the other 100 were apparently healthy volunteers who acted as the control group. Complete blood count, liver function test, kidney function tests, TAT complex, PAP complex, ß-TG as indicators of coagulation changes, serum zinc and copper were performed on all participants. RESULTS: Significantly higher levels of TAT complex, PAP complex and ß-TG in thalassemia children than the controls. Decreased serum zinc and increased serum copper levels in thalassemia children compared to the controls. A negative correlation was observed between the serum level of TAT and hemoglobin level, besides the negative correlation of TAT complex and ß-TG with the serum zinc. CONCLUSION: Thalassemia major was associated with increased serum level of coagulation activation markers, increased serum copper while decreased serum zinc.

Serum Endocan Levels and Subclinical Atherosclerosis in Patients with Chronic Kidney and End-Stage Renal Diseases.

Results: HD and CKD groups had significantly higher endocan levels when compared with control group (median (IQR): 519.0 (202.3-742.0) versus 409.0 (245.3-505.3) and 273.0 (168.0-395.5) ng/L, respectively). Also, HD patients had significantly higher endocan levels when compared with CKD levels. HD patients had significantly higher carotid intima-media thickness (CIMT) when compared with CKD patients (median (IQR): 0.80 (0.80-0.90) versus 0.75 (0.73-0.75) mm, p < 0.001). HD patients had significantly higher frequency of SCA when compared with CKD patients (46.7% versus 13.3%, p=0.005). Patients with SCA had significantly higher hsCRP (median (IQR): 36.5 (26.8-43.5) versus 24.0 (15.8-29.0) mg/dl) and endocan levels (697.0 (528.3-974.8) versus 222.5 (158.8-565.8) ng/L) when compared with patients without SCA. ROC curve analysis of endocan for identification of SCA in HD patients showed that at a cutoff of 380.5 ng/L, endocan has an AUC of 0.862 with a sensitivity and specificity of 92.9% and 68.7%, respectively. Conclusions: Serum endocan levels are related to SCA in HD patients. In addition, it is associated with the hyperinflammatory state in those patients.