Historically, the long-held protein-centered bias has denoted 98% of the human genome as ‘Junk’ DNA. However, the current work has shifted the perception of such 'junk' transcriptional products to functional regulatory molecules. The recent surveillance of the human transcriptome has highlighted the pivotal role of such non-coding RNA (ncRNA) molecules in diverse physiological and pathological conditions. Long non-coding RNA (lncRNA) is a recent class of ncRNA molecules that is still in its infancy stage. The main focus of this review is to unravel the importance of lncRNAs in the most prevalent malignancy among females which is Breast Cancer (BC). A specific focus on lncRNAs as prognostic markers among BC patients showing molecular subtype heterogeneity was also tackled in this review. Finally, the functional and the mechanistic roles of such booming ncRNA molecules in shaping the fate of the BC progression have been highlighted.

l-Arginine is one of the most metabolically versatile amino acids. In addition to its role in the synthesis of nitric oxide, l-arginine serves as a precursor for the synthesis of polyamines, proline, glutamate, creatine, agmatine and urea. Several human and experimental animal studies have indicated that exogenous l-arginine intake has multiple beneficial pharmacological effects when taken in doses larger than normal dietary consumption. Such effects include reduction in the risk of vascular and heart diseases, reduction in erectile dysfunction, improvement in immune response and inhibition of gastric hyperacidity. This review summarises several positive studies and personal experiences of l-arginine. The demonstrated anti-aging benefits of l-arginine show greater potential than any pharmaceutical or nutraceutical agent ever previously discovered.

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Fenugreek and Balanites are two plants commonly used in Egyptian folk medicine as hypoglycemic agents. In the present study, the effects of 21 days oral administration of Fenugreek seed and Balanites fruit extracts (1.5 g/kg bw) on the liver and kidney glycogen content and on some key liver enzymes of carbohydrate metabolism in STZ-diabetic rats were studied. In addition, the effects of these two plant extracts on the intestinal alpha-amylase activity in vitro and starch digestion and absorption in vivo were also examined. Results indicated that single injection of STZ (50 mg/kg bw) caused 5-folds increase in the blood glucose level, 80% reduction in serum insulin level, 58% decrease in liver glycogen and 7-folds increase in kidney glycogen content as compared to the normal levels. The activity of glucose-6-phosphatase was markedly increased, whereas, the activities of both glucose-6-phosphate dehydrogenase and phospho-fructokinase were significantly decreased in the diabetic rat liver. Administration of Fenugreek extract to STZ-diabetic rats reduced blood glucose level by 58%, restored liver glycogen content and significantly decreased kidney glycogen as well as liver glucose-6-phosphatase activity. Meanwhile, Balanites extract reduced blood glucose level by 24% and significantly decreased liver glucose-6-phosphatase activity in diabetic rats. On the other hand, our results demonstrated that both the Fenugreek and Balanites extracts were able to in vitro inhibit alpha-amylase activity in dose-dependent manner. Fenugreek was more potent inhibitor than Balanites. This inhibition was reversed by increasing substrate concentration in a pattern which complies well with the effect of competitive inhibitors. Furthermore, this in vitro inhibition was confirmed by in vivo suppression of starch digestion and absorption induced by both plant extracts in normal rats. These findings suggest that the hypoglycemic effect of Fenugreek and Balanites is mediated through insulinomimetic effect as well as inhibition of intestinal alpha-amylase activity.

Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype. Among young females, TNBC is the leading cause of cancer-related mortalities. Recently, long noncoding RNAs (lncRNAs) are representing a promising pool of regulators for tuning the aggressiveness of several solid malignancies. However, this still needs further investigations in TNBC. The main aim of this study is to unravel the expression pattern of sONE lncRNA and its mechanistic role in TNBC. Results showed that sONE is restrictedly expressed in TNBC patients; its expression level is inversely correlated with the aggressiveness of the disease. sONE acts as a posttranscriptional regulator to endothelial nitric oxide synthase (eNOS) and thus affecting eNOS-induced nitric oxide (NO) production from TNBC cells measured by Greiss reagent. Mechanistically, sONE is a potential tumor suppressor lncRNA in TNBC cells; repressing cellular viability, proliferation, colony-forming ability, migration, and invasion capacities of MDA-MB-231. Furthermore, sONE effects were found to be extended to affect the maestro tumor suppressor TP53 and the oncogenic transcription factor c-Myc. Knocking down of sONE resulted in a marked decrease in TP53 and increase in c-Myc and consequently altering the expression status of their downstream tumor suppressor microRNAs (miRNAs) such as miR-34a, miR-15, miR-16, and let-7a. In conclusion, this study highlights sONE as a downregulated tumor suppressor lncRNA in TNBC cells acting through repressing eNOSinduced NO production, affecting TP53 and c-Myc proteins levels and finally altering the levels of a panel of tumor suppressor miRNAs downstream TP53/c-Myc proteins. K E Y W O R D S eNOS, long noncoding RNAs, microRNAs, nitric oxide, sONE, triple-negative breast cancer SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Youness RA, Hafez HM, Khallaf E, Assal RA, Abdel Motaal A, Gad MZ. The long noncoding RNA sONE represses triple-negative breast cancer aggressiveness through inducing the expression of miR-34a, miR-15a, miR-16, and let-7a.