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This study investigates the interrelationship between human telomerase reverse transcriptase (hTERT) and ferroptosis in precursor-B (pre-B) acute lymphoblastic leukemia (ALL), specifically examining how hTERT modulation affects ferroptotic cell death pathways. Given that hTERT overexpression characterizes various cancer phenotypes and elevated telomerase activity is observed in early-stage and relapsed ALL, we investigated the molecular mechanisms linking hTERT regulation and ferroptosis in leukemia cells. The experimental design employed Nalm-6 and REH cell lines under three distinct conditions: curcumin treatment, hTERT siRNA knockdown, and their combination. Cell viability and proliferation were assessed via MTT and BrdU assays at 24- and 48-hour intervals post-treatment. Ferroptotic and oxidative markers were quantified using commercial assays, while cell death parameters and gene expression were evaluated through flow cytometry and qRT-PCR analyses. Molecular docking studies were performed to evaluate protein-ligand interactions. Results demonstrated that combined curcumin treatment and hTERT knockdown significantly enhanced cytotoxicity in Nalm-6 cells compared to individual interventions. This was characterized by the upregulation of ferroptosis promoters (lipid-ROS, Fe²⁺, ACSL4) and suppression of inhibitors (GSH, GPx, SLC7A11, GPx4). The response showed cell-line specificity, with Nalm-6 cells exhibiting enhanced ferroptotic sensitivity while REH cells underwent apoptotic cell death. Molecular docking revealed strong curcumin-protein interactions (∆G = -34.24 kcal/mol for hTERT). This study establishes hTERT as a critical regulator of ferroptotic cell death in pre-B ALL, operating through redox homeostasis, iron metabolism, and lipid peroxidation pathways. The cell-type-specific responses suggest promising therapeutic strategies through combined hTERT suppression and ferroptosis induction. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress induced by superoxide anion plays critical roles in the pathogenesis of coronary artery disease (CAD) and hence acute myocardial infarction (AMI). The major source of superoxide production in vascular smooth muscle and endothelial cells is the NADPH oxidase complex. An essential component of this complex is p22phox, that is encoded by the cytochrome b-245, Alpha polypeptide (CYBA) gene. The aim of this study was to investigate the association of CYBA variants (rs1049255 and rs4673) and premature acute myocardial infarction risk in an Iranian population. Methods: The study population consisted of 158 patients under the age of 50 years, with a diagnosis of premature AMI, and 168 age-matched controls with normal coronary angiograms. Genotyping of the polymorphisms was performed by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results: There was no association between the genotypes and allele frequencies of rs4673 polymorphism and premature acute myocardial infarction (P> 0.05). A significant statistical association was observed between the genotypes distribution of rs1049255 polymorphism and AMI risk (P= 0.037). Furthermore, the distribution of AA+ AG /G G genotypes was found to be statistically significant between the two groups (P= 0.011). Conclusions: Our findings indicated that rs1049255 but not rs4673 polymorphism is associated with premature AMI.

Traditional medicines remain a source of potential for discovering of new compounds with valuable pharmacological activities. Leaves of Ficus carica were dried, powdered and extracted using methanol (ME). An aliquot of ME was dried and re-extracted by water:chloroform and the other aliquot by water: peteruleum ether. Effect of aqueous fractions of the former (ACR; 0.08, 0.1 and 0.13 mg d[L.sup.1]), the latter (APR; 0.07, 0.1 and 0.15 mg d[L.sup.1]) and ME (0.03, 0.05 and 0.08 mg d[L.sup.1]) of Ficus carica leaf on the secretion and cell content of cholesterol in HepG2 cells were studied. Extracts were added to the media in both basal and glucose stimulated conditions and incubated for 48h.While glucose significantly increased cholesterol secretion (17[+ or -]0.76 mg d[L.sup.1]) vs basal condition (6.91[+ or -]0.66 mg d[L.sup.1]), co-incubation with extracts reduced secretion of cholesterol in many concentrations of the stimulated condition. On the other hand, cholesterol content of HepG2 in glucose stimulated condition (2.73[+ or -]0.39 mg d[L.sup.1]) showed significant increase compared to the basal status (1.96[+ or -]0.14 mg d[L.sup.1]) (p Key words: Ficus carica, leaf extract, cholesterol, INTRODUCTION Hypercholesterolemia is one of the major risk factors in development of coronary artery disease in recent years [2,6]. Nowadays; many non-prescribed treatments have been available for lowering the cholesterol. [...]

Recognition of the molecular mechanisms of cAMP action against DNA damage-induced apoptosis can be useful to improve the efficacy of DNA damaging therapeutic agents. Considering the critical role of bcl-2-associated death promoter (BAD) and p53 proteins in DNA damage -induced apoptosis, the aim of this study was to assess the effect of cAMP-elevating agents on these proteins in doxorubicin-treated pre-B acute lymphoblastic leukemia (pre-B ALL) NALM-6 cells.The pre-B ALL cell line NALM-6 was cultured and treated with doxorubicin in combination with or without cAMP-elevating agents forskolin and 3-isobutyl-1-methylxanthine (IBMX). Cell viability was measured by trypan blue staining and MTT assay. For evaluation of apoptosis, annexin-V staining by flow cytometry and caspase-3 activity assay were used. Protein expression of p53, BAD and phoshorylated BAD was detected by western blotting analysis.cAMP-increasing agents diminished the doxorubicin-mediated cytotoxicity in NALM-6 cells as indicated by the viability assays. Annexin-V apoptosis assay showed that the cAMP-elevating agents decreased doxorubicin-induced apoptosis. Moreover, doxorubicin-induced caspase-3 activity was attenuated in the presence of cAMP-increasing agents. Western blot results revealed the reduced expression of p53 protein in cells treated with combination of cAMP-elevating agents and doxorubicin in contrast to cells treated with doxorubicin alone. Expression of total BAD protein was not affected by doxorubicin and cAMP-elevating agents. However, phosphorylation of BAD protein was induced in the presence of cAMP-elevating agents. Our study suggests that elevated cAMP levels inhibit doxorubicin-induced apoptosis in pre-B ALL cells through induction of BAD phosphorylation and abrogation of p53 accumulation.