Background: Worldwide, hepatocellular carcinoma (HCC) is a universal problem and its epidemiological data showed variation from place to place. Hepatocellular carcinoma (HCC) is the sixth and fourth common cancer in worldwide and Egypt, respectively. Egypt ranks the third and 15 th most populous country in Africa and worldwide, respectively. The aim of this review is to compare the status of HCC in Egypt to that in the worldwide from different issues; risk factors, screening and surveillance, diagnosis and treatment, prevention, as well as research strategy. Main body: The risk factors for HCC in Egypt are of great importance to be reported. The risk factor for HCC are either environmental-or host/genetic-related risk factors. In the last years, there is a tangible improvement of both screening and surveillance strategies of HCC in Egypt. The unprecedented national screening campaign launched by the end of 2018 is a mirror image of this improvement. While the improvement of the HCC prevention requires the governmental health administration to implement health policies. Although the diagnosis of Egyptian HCC patients follows the international guidelines but HCC treatment options are limited in terms of cost. In addition, there are limited Egyptian reports about HCC survival and relapse. Both basic and clinical HCC research in Egypt are still limited compared to worldwide. Short conclusion: Deep analysis and understanding of factors affecting HCC burden variation worldwide help in customization of efforts exerted to face HCC in different countries especially large country like Egypt. Overall, the presence of a research strategy to fight HCC in Egyptian patients will help in the optimum allocation of available resources to reduce the numbers of HCC cases and deaths and to improve the quality of life.

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Although integrin alpha 2 subunit (ITGA2) mediates cancer progression and metastasis, its transfer by exosomes has not been investigated in prostate cancer (PCa). We aimed to determine the role of exosomal ITGA2 derived from castration-resistant PCa (CRPC) cells in promoting aggressive phenotypes in androgen receptor (AR)-positive cells. Exosomes were co-incubated with recipient cells and tested for different cellular assays. ITGA2 was enriched in exosomes derived from CRPC cells. Co-culture of AR-positive cells with CRPC-derived exosomes increased their proliferation, migration, and invasion by promoting epithelial-mesenchymal transition, which was reversed via ITGA2 knockdown or inhibition of exosomal uptake by methyl-β-cyclodextrin (MβCD). Ectopic expression of ITGA2 reproduced the effect of exosomal ITGA2 in PCa cells. ITGA2 transferred by exosomes exerted its effect within a shorter time compared to that triggered by its endogenous expression. The difference of ITGA2 protein expression in localized tumors and those with lymph node metastatic tissues was indistinguishable. Nevertheless, its abundance was higher in circulating exosomes collected from PCa patients when compared with normal subjects. Our findings indicate the possible role of the exosomal-ITGA2 transfer in altering the phenotype of AR-positive cells towards more aggressive phenotype. Thus, interfering with exosomal cargo transfer may inhibit the development of aggressive phenotype in PCa cells.

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Endoplasmic reticulum (ER) stress was reported to play a major role in non‐alcoholic fatty liver disease (NAFLD) induction and progression. Here, we study the effect of Zingiber officinale and omega‐3 fatty acids on ER stress for treating NAFLD. Male Wistar rats were fed on a normal diet (control group) or high‐fat diet (HFD) for 8 weeks. The HFD rats were later treated with vehicle, omega‐3 or with Z. officinale extract. HFD group demonstrated significantly more body weight gain and higher plasma lipid profile, glucose, and hepatic enzymes. The expressions of lipogenic ChREBP and ER stress genes CHOP, XBP1, and GRP78 were increased. This was accompanied by intrahepatic fat accumulation visualized by hepatic morphology and H&E‐stained sections. Treatment with Z. officinale and omega‐3 fatty acids reverted these changes into a normal healthy state. From these results, we prove that both therapeutic approaches can be potential drugs for treating NAFLD besides other ER stress‐associated diseases. Practical applications The effect of Zingiber officinale extract and omega‐3 fatty acid on ER stress associated with NAFLD was investigated. The results revealed that Z. officinale extract and omega‐3 fatty acids significantly inhibited ER stress and intrahepatic fat accumulation with the upper hand for Z. officinale extract. Both can be used as future promising therapies for the treatment of NAFLD patients and also treating different diseases that involve ER stress as a pathological modulator like diabetes mellitus, Alzheimer's disease, Parkinson's disease, and cancer.

SAPK-JNK pathway performs a significant role in the pathogenesis of type 2 diabetes. Balanites aegyptiaca (BA) is used as an anti-diabetic agent in folk medicine however its hypoglycemic mechanism is not fully elucidated. The current study aimed to evaluate the effect of crude extract, butanol, and dichloromethane fractions from BA on the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK-JNK) pathway in experimental diabetic rats. Six groups of male Wistar rats were included: normal control, diabetic, diabetic rats treated with crude, butanol or dichloromethane fraction from BA (50 mg/kg BW) and diabetic rats treated with gliclazide as a reference drug for one month. Our results suggested a protective role of treatment of diabetic rats with BA against oxidative stress-induced SAPK-JNK pathway. Moreover, BA treatment produced a reduction in plasma glucose, HbA, lactic acid, lipid profile, malondialdehyde levels and produced an increase in insulin, reduced glutathione levels, catalase and superoxide dismutase activities compared with untreated diabetic rats. Moreover, it decreased apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase 1, protein 53 and increased insulin receptor substrate 1 in rat pancreas while it increased glucose transporter 4 in rat muscle. Analysis of BA extracts by LC-HRMS revealed the presence of different saponins with reported hypoglycemic effect. In conclusion, BA exerted hypoglycemic, hypolipidemic, insulinotropic and antioxidant effects. Additionally, it reduced apoptosis in pancreatic β-cells and increased glucose uptake in muscle. These results suggest that the hypoglycemic effect of BA is due to the inhibition of the SAPK-JNK pathway.

BackgroundThe interaction of advanced glycation end products (AGEs) and its receptor (RAGE) has played an important role in the pathogenesis of diabetes and its complications. A soluble form of RAGE (sRAGE) has been reported as a decoy receptor for AGEs. Oxidative stress is demonstrated in pathological condition such as atherosclerosis and diabetes mellitus. It has been suggested to be involved in the pathogenesis of both macro- and microvascular complications. This study was designed to evaluate the effect of glycemic control on sRAGE and oxidative stress markers in type 2 diabetic patients.MethodsSeventy patients with type 2 diabetes and 20 healthy subjects were recruited into the study. Blood glutathione (GSH) and plasma total nitric oxide (NOx) levels were measured using commercially available colorimetric kits, blood superoxide dismutase (SOD) activity was measured by the method of Marklund and Marklund, and plasma C-peptide, oxidized LDL (ox-LDL), sRAGE, and VCAM-1 levels were measured using competitive ELISA kits.ResultsPlasma sRAGE levels were significantly lower (p < 0.05) while VCAM-1 levels were significantly higher (p < 0.05) in poorly controlled diabetic patients compared with healthy control. Blood GSH levels were significantly lower in diabetic patients compared with healthy control (p < 0.05). Plasma C-peptide, NOx, ox-LDL levels, and SOD activity were not significantly different in diabetic patients compared with healthy control. Plasma levels of sRAGE were negatively associated with circulating VCAM-1 levels in diabetic patients.ConclusionPoor glycemic control decreases plasma sRAGE and increases VCAM-1 levels while good glycemic control improves these abnormalities which provides benefit to diabetic patients.