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Circulating microRNAs are deregulated in liver fibrosis and hepatocellular carcinoma (HCC) and are candidate biomarkers. This study investigated the potential of serum microRNAs; miR-19a, miR-296, miR-130a, miR-195, miR-192, miR-34a, and miR-146a as early diagnostic biomarkers for hepatitis C virus (HCV)-related HCC. As how these microRNAs change during liver fibrosis progression is not clear, we explored their serum levels during fibrosis progression in HCV-associated chronic liver disease (CLD) and if they could serve as non-invasive biomarkers for fibrosis progression to HCC. 112 Egyptian HCV-HCC patients, 125 non-malignant HCV-CLD patients, and 42 healthy controls were included. CLD patients were subdivided according to Metavir fibrosis-scoring. Serum microRNAs were measured by qRT-PCR custom array. Serum microRNAs were deregulated in HCC versus controls, and except miR-130a, they were differentially expressed between HCC and CLD or late fibrosis (F3-F4) subgroup. Serum microRNAs were not significantly different between individual fibrosis-stages or between F1-F2 (early/moderate fibrosis) and F3-F4. Only miR-19a was significantly downregulated from liver fibrosis (F1-F3) to cirrhosis (F4) to HCC. Individual microRNAs discriminated HCC from controls, and except miR-130a, they distinguished HCC from CLD or F3-F4 patients by receiver-operating-characteristic analysis. Multivariate logistic analysis revealed a panel of four microRNAs (miR-19a, miR-195, miR-192, and miR-146a) with high diagnostic accuracy for HCC (AUC = 0.946). The microRNA panel also discriminated HCC from controls (AUC = 0.949), CLD (AUC = 0.945), and F3-F4 (AUC = 0.955). Studied microRNAs were positively correlated in HCC group. miR-19a and miR-34a were correlated with portal vein thrombosis and HCC staging scores, respectively. In conclusion, studied microRNAs, but not miR-130a, could serve as potential early biomarkers for HCC in high-risk groups, with miR-19a as a biomarker for liver fibrosis progression to cirrhosis to HCC. We identified a panel of four serum microRNAs with high accuracy in HCC diagnosis. Additional studies are required to confirm this panel and test its prognostic significance.

Background/objectiveZingiber officinale Roscoe (ginger) (Zingiberaceae) has been cultivated for thousands of years both as a spice and for medicinal purposes. Ginger rhizomes successive extracts (petroleum ether, chloroform and ethanol) were examined against liver fibrosis induced by carbon tetrachloride in rats.ResultsThe evaluation was done through measuring antioxidant parameters; glutathione (GSH), total superoxide dismutase (SOD) and malondialdehyde (MDA). Liver marker enzymes; succinate and lactate dehydrogenases (SDH and LDH), glucose-6-phosphatase (G-6-Pase), acid phosphatase (AP), 5'- nucleotidase (5'NT) and liver function enzymes; aspartate and alanine aminotransferases (AST and ALT) as well as cholestatic markers; alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin were estimated. Liver histopathological analysis and collagen content were also evaluated. Treatments with the selected extracts significantly increased GSH, SOD, SDH, LDH, G-6-Pase, AP and 5'NT. However, MDA, AST, ALT ALP, GGT and total bilirubin were significantly decreased.ConclusionsExtracts of ginger, particularly the ethanol one resulted in an attractive candidate for the treatment of liver fibrosis induced by CCl4. Further studies are required in order to identify the molecules responsible of the pharmacological activity.

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This study investigated the involvement of neutrophil infiltration, nitric oxide (NO) generation, and oxidative stress in indomethacin-induced ulcer and the possible gastroprotective potentials of spermine and taurine, known for their tissue regenerating and antioxidant effects, respectively. Male Wistar albino rats (180-220 g) were allocated into a normal control group, ulcer control group (received a single dose of indomethacin 40 mg-kg p.o.), and two ulcer groups pretreated with spermine (150 mg-kg p.o. 1 h before ulcer induction) and taurine (250 mg-kg i.p. for three consecutive days before ulcer induction). The animals were killed 6 h after indomethacin administration, and the gastric juice, serum, and mucosal tissue were used for gastric injury evaluation. Both modulators significantly ameliorated the indomethacin-induced gastric lesions in glandular mucosa. Notably, spermine exhibited the most pronounced effect as manifested by great reduction in the gastric ulcer index, normalization of the elevated gastric acidity, and triggering of mucin production. Spermine and taurine were able to decrease the elevated levels of gastric myeloperoxidase, conjugated diene, and serum NO. However, the lowered tissue NO content was markedly elevated only by taurine. The antioxidant action of taurine was illustrated by restoration of the depressed content of glutathione, normalization of the inhibited activities of glutathione reductase, and superoxide dismutase. These results suggest that spermine and taurine confer significant gastroprotection against indomethacin-induced gastric injury with the priority of spermine.

Cardiovascular diseases (CVD) are the leading cause of death in the diabetic population. Obesity is a serious problem that has been linked with CVD and diabetes via a variety of adipokines. The aims of this study were to evaluate and correlate circulating chemerin, apelin, vaspin, and omentin-1 levels in obese type 2 diabetic Egyptian patients with coronary artery stenosis (CAS), and to assess their usefulness as noninvasive diagnostic biomarkers. Chemerin, apelin, vaspin, and omentin-1 levels were determined by enzyme immunoassay in coronary artery disease (CAD) I patients (45 non-obese, nondiabetic with CAS), CAD II patients (45 obese, diabetic with CAS), and 30 controls. Patients in CAD I and CAD II groups exhibited higher levels of chemerin and apelin together with lower levels of vaspin and omentin-1 than in controls. These alterations were more significant in CAD II than in CAD I patients. Additionally, adipokine levels were individually correlated with each other and with certain biochemical variables. Moreover, chemerin and vaspin levels could differentiate CAD II patients from CAD I and controls. Alterations of these adipokines may play a crucial role in the pathogenesis of CAS in obese type 2 diabetic Egyptian patients. Chemerin and vaspin could be used as markers to support diagnosis of CAS.

Zizyphus is one of the plants commonly used in Egyptian folk medicine for the treatment of different diseases. The present study aims to investigate the effect of the butanol extract of Zizyphus spina-christi leaves as well as christinin-A, its principle saponin glycoside, in normal and streptozotocin-diabetic rats. In normal rats, treatment in both cases for one and four weeks produced insignificant changes in all studied parameters. However, in diabetic rats, both treatments significantly reduced serum glucose level, liver phosphorylase and glucose-6-phosphatase (G-6-pase) activities, and significantly increased serum pyruvate level and liver glycogen content after 4 weeks treatment. There was also marked improvement in glucose utilization in diabetic rats in both cases. Serum insulin and pancreatic cAMP levels showed significant increases in diabetic rats treated for a period of 4 weeks with the butanol extract.