miR-214 aggravates oxidative stress in thalassemic erythroid cells by targeting ATF4.

Oxidative damage to erythroid cells plays a key role in the pathogenesis of thalassemia. The oxidative stress in thalassemia is potentiated by heme, nonheme iron, and free iron produced by the Fenton reaction, due to degradation of the unstable hemoglobin and iron overload. In addition, the levels of antioxidant enzymes and molecules are significantly decreased in erythrocytes in α- and ß-thalassemia. The control of oxidative stress in red blood cells (RBCs) is known to be mediated by microRNAs (miRNAs). In erythroid cells, microR-214 (miR-214) has been reported to respond to external oxidative stress. However, the molecular mechanisms underlying this phenomenon remain unclear, especially during thalassemic erythropoiesis. In the present study, to further understand how miR-214 aggravates oxidative stress in thalassemia erythroid cells, we investigated the molecular mechanism of miR-214 and its regulation of the oxidative status in thalassemia erythrocytes. We have reported a biphasic expression of miR-214 in ß- and α-thalassemia. In the present study the effect of miR-214 expression was investigated by using miR -inhibitor and -mimic transfection in erythroid cell lines induced by hemin. Our study showed a biphasic expression of miR-214 in ß- and α-thalassemia. Subsequently, we examined the effect of miR-214 on erythroid differentiation in thalassemia. Our study reveals the loss-of-function of miR-214 during translational activation of activating transcription factor 4 mRNA, leading to decreased reactive oxygen species levels and increased glutathione levels in thalassemia erythroid cell. Our results suggest that the expression of activating transcription factor 4 regulated by miR-214 is important for oxidative stress modulation in thalassemic erythroid cells. Our findings can help to better understand the molecular mechanism of miRNA and transcription factors in regulation of oxidative status in erythroid cells, particularly in thalassemia, and could be useful for managing and relieving severe anemia symptoms in patients in the future.

Phytochemical Composition and Bioactivities of Aqueous Extract of Rambutan (Nephelium lappaceum L. cv. Rong Rian) Peel.

Thailand is one of the leading exporting countries of rambutan and rambutan peels are considered as a biological waste. In this study, rambutan (Nephelium lappaceum L. cv. Rong Rian) peel extracts (RPE) obtained by water extraction were analyzed for their phytochemical composition, antibacterial and antioxidant activities, and cytotoxicity. The bioactive compounds in RPE identified by GC-MS were mome inositol (35.99 mg/g), catechol (29.37 mg/g), 5-hydroxymethylfurfural (5.69 mg/g), 2-pentenal, (E)-(5.22 mg/g), acetic acid (3.69 mg/g), 1,2,3-propanetriol (3.67 mg/g), 2-furan-carboxaldehyde (2.66 mg/g), and other compounds. FT-IR analysis confirmed the presence of alcohol and phenol in the extract. Antibacterial activities of RPE against food pathogenic and spoilage bacteria showed that RPE could inhibited Bacillus subtilis, B. cereus, Staphylococcus aureus, Vibrio cholerae, V. parahaemolyticus, Pseudomonas aeruginosa, and P. fluorescens, with MIC values ranging between 1024 and 8192 µg/mL. The extract also showed antioxidant properties, as determined by DPPH and ABTS assays. The cytotoxicity analysis after 72 h of treatment showed the IC50 values at 194.97 ± 4.87, 205.92 ± 2.55, and 94.11 ± 1.33 µg/mL for L929, Vero, and MCF-7 cell lines, respectively. Therefore, this study provided a basis of knowledge of rambutan peels as an excellent source of natural bioactive compounds for various applications.