Introduction: Cancer is one of the most difficult challenges faced by humanity due to its many associated issues, such as inability to prevent diseases, treatment safety, and high mortality rate. In cancer, a variety of cellular signaling is activated to ensure malignancy transformation, angiogenesis and metastasis. The most efficient signaling pathway in cancer is mitogen-activated protein kinase (MAPK), which controls malignancy and regulates apoptosis.Methods: Four different flavonoid glycosides have been isolated from Pulicaria jaubertii using the phytochemical characterization of hydro-methanol extract. The purified glycosides (PJs) were investigated for their potential repression of cancer development using human lung epithelial cells and hepatocellular carcinoma (HCC) and compared with Sorafenib (SOR), the standard systemic drug for HCC. In PJ-treated cells, the expression profile of K-Ras, B-Raf, and P53 were detected using qRT-PCR, flow cytometry, confocal microscopy and western blot. Steady-state mRNA and levels of transforming growth factor-beta (TGF-β) and interleukin 8 (IL-8) were monitored in the fluids media at different time points following treatment.Results: Our results showed that the qurictine glycosides (PJ-1 and PJ-9) selectively inhibited the mutant K-Ras/B-Raf proteins expression and interaction in both cancer cells; while SOR showed obvious depletion of total Raf-1 protein in cancer cells and normal cells as well. Interestingly, the combination of PJ-1 or PJ-9 with SOR exhibited restoring cell viability of normal cells via controlling Raf-1 and P53 genes expression. Further, these identified PJ agents significantly adjusted the levels of TGF-β and IL-8 in cancer treated cells accompanied by restoring the activation of P53 expression. These findings were confirmed by docking analysis of PJs ligand and the crystal structure of K-Ras, B-Raf, and ERK transcription factor.Conclusion: The current data provide novel and natural multi-kinase inhibitors with competitive regulation of the mutant proteins; K-Ras and B-Raf and sustained MAPK signaling without any detectable toxic effect in normal cells.

Background and Objectives. SAA is an acute-phase reactant detected during an FMF attack or other inflammatory conditions. High SAA levels may increase the risk of amyloidosis. The aim of the study is to measure the serum amyloid A (SAA) level in a group of Egyptian children with familial Mediterranean fever (FMF) and study its various correlates, if any. Methods. The study enrolled seventy-one children with FMF. Results. SAA level was high in 78.9% of the studied patients with a mean of 81.62 ± 31.6 mg/L, and CRP was positive in 31% of patients. There was no significant releation between SAA level and any demographic or clinical manifestation. High SAA was more frequent in V726A allele (16.9%) followed by M694V allele (12.3%). Elevated SAA levels were more frequent in patients on low colchicine doses. Forty-five percent (45%) of patients have low adherence to colchicine therapy. Interpretation and Conclusion. High SAA levels were detected two weeks after last FMF attack in a large percentage of Egyptian FMF children. This indicates that subclinical inflammation continues during attack-free periods, and SAA could be used as a marker of it.

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There are very few published reports on the causes of chronic kidney disease (CKD) in Egyptian children. We reviewed the records of 1018 (males 56.7%, age ranged from 1 to 19 years) Egyptian patients suffering from CKD and followed-up at the pediatric nephrology units (outpatient clinics and dialysis units) of 11 universities over a period of two years. The mean of the estimated glomerular filtration rate was 12.5 mL/min/1.73 m 2 . Children with CKD stage I and stage II comprised 4.4% of the studied group, while those with stage III, IV and V comprised 19.7%, 18.3% and 57.6%, respectively. The most common single cause of CKD was obstructive uropathy (21.7%), followed by primary glomerulonephritis (15.3%), reflux/urinary tract infection (14.6%), aplasia/hypoplasia (9.8%) and familial/metabolic diseases (6.8%); unknown causes accounted for 20.6% of the cases. Of the 587 patients who had reached end-stage renal disease, 93.5% was treated with hemodialysis and only 6.5% were treated with peritoneal dialysis.