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Introduction Mutations in the HFE gene have been shown to be associated with hemochromatosis which is observed in beta-thalassemia major. In this study, we determined the HFE gene mutations (C282Y and H63D) among b-thalassemia major patients to investigate the effect of these mutations on serum Ferritin levels. Material and methods In this cross-sectional study, a total of 105 b-thalassemia subjects with a history of regular blood transfusion were selected. They divided into two distinct groups according cut off 1000 ng/ml of serum Ferritin levels. The HFE gene mutant allele detected by RFLP-PCR. Results Of 105 thalassemia patients, 29 patients (14 male and 15 female) were heterozygote for H63D mutation, and just one male was homozygote, but for C282Y mutation just one heterozygote and one homozygote was detected, and overall 31% had coexistence of b-thal and HFE gene mutations. As expected, Ferritin levels significantly differed between groups (P = 0.001). Conclusion The impact of detection of HFE mutations could prognosis the likelihood of iron overload in multi-transfused patients, and allowing early diagnosis and proper management to overcome complications of iron overload in beta-thalassemia patients.

Sirtuins are key players for maintaining cellular homeostasis and are often deregulated in different human diseases. SIRT7 is the only member of mammalian sirtuins that principally resides in the nucleolus, a nuclear compartment involved in ribosomal biogenesis, senescence, and cellular stress responses. The ablation of SIRT7 induces global genomic instability, premature ageing, metabolic dysfunctions, and reduced stress tolerance, highlighting its critical role in counteracting ageing-associated processes. In this review, we describe the molecular mechanisms employed by SIRT7 to ensure cellular and organismal integrity with particular emphasis on SIRT7-dependent regulation of nucleolar functions.

Giant cell arteritis (GCA), medium and large vessel granulomatous vasculitis affecting the elderly, is characterized by a multitude of vascular complications, including venous thrombosis, myocardial infraction and stroke. The formation of granulomatous infiltrates and the enhanced accumulation of proinflammatory cytokines are typical features of this condition. The GCA pathogenesis remains largely unknown, but recent studies have suggested the involvement of oxidative stress, mainly sustained by an enhanced reactive oxygen species (ROS) production by immature neutrophils. On this basis, in the present study, we intended to evaluate, in GCA patients, the presence of systemic oxidative stress and possible alterations in the expression level of nuclear sirtuins, enzymes involved in the inhibition of inflammation and oxidative stress. Thirty GCA patients were included in the study and compared to 30 healthy controls in terms of leukocyte ROS production, oxidative stress and SIRT1 expression. Our results clearly indicated a significant increase (p < 0.05) both in the ROS levels in the leukocyte fractions and plasma oxidative stress markers (lipid peroxidation and total antioxidant capacity) in the GCA patients compared to the healthy controls. In PBMCs from the GCA patients, a significant decrease in SIRT1 expression (p < 0.05) but not in SIRT6 and SIRT7 expression was found. Taken together, our preliminary findings indicate that, in GCA patients, plasma oxidative stress is paralleled by a reduced SIRT1 expression in PBMC. Further studies are needed to highlight if and how these alterations contribute to GCA pathogenesis.

Adaptation to different forms of environmental stress is crucial for maintaining essential cellular functions and survival. The nucleolus plays a decisive role as a signaling hub for coordinating cellular responses to various extrinsic and intrinsic cues. p53 levels are normally kept low in unstressed cells, mainly due to E3 ubiquitin ligase MDM2-mediated degradation. Under stress, nucleophosmin (NPM) relocates from the nucleolus to the nucleoplasm and binds MDM2, thereby preventing degradation of p53 and allowing cell-cycle arrest and DNA repair. Here, we demonstrate that the mammalian sirtuin SIRT7 is an essential component for the regulation of p53 stability during stress responses induced by ultraviolet (UV) irradiation. The catalytic activity of SIRT7 is substantially increased upon UV irradiation through ataxia telangiectasia mutated and Rad3 related (ATR)-mediated phosphorylation, which promotes efficient deacetylation of the SIRT7 target NPM. Deacetylation is required for stress-dependent relocation of NPM into the nucleoplasm and MDM2 binding, thereby preventing ubiquitination and degradation of p53. In the absence of SIRT7, stress-dependent stabilization of p53 is abrogated, both in vitro and in vivo, impairing cellular stress responses. The study uncovers an essential SIRT7-dependent mechanism for stabilization of the tumor suppressor p53 in response to genotoxic stress.

Background: Differential expression profile of microRNAs (miRNAs) could be a diagnosis signature for monitoring gastric cancer (GC) progression. In this study, we focus on the comparison of expression levels of miR-21, miR-25, miR-93, miR-106b, and miR-375 during the sequential pattern of GC development, including normal gastric, gastric dysplasia, and GC sample. Methods: We used SYBR Green-based quantitative-PCR to quantify miRNAs expression. Results: Our analysis revealed the increased expression levels of miR-21 (p = 0.034), miR-25 (p = 0.0003), miR-93 (p = 0.0406), and miR-106b (p = 0.023) in GC samples. In addition, GC patients with positive lymph node metastasis showed the up-regulation of miR-25, miR-93, and miR-106b (p < 0.05). Conclusion: Our findings suggested that the expression of miR-21, miR-25, miR-93, and miR-106b altered in GC, and some of them may be further investigated as biomarkers for GC early detection and prognosis prediction.

Coronary Artery Disease (CAD) is one of the most widespread non-communicable diseases. Vitamin Dbinding protein (VDBP) and its genetic poly morphisms have been highlighted as the susceptible components for CAD. The aim of the present study was to examine the association of VDBP single nucleotide poly morphisms (SNPs) - rs7041 and rs4588 - with CAD susceptibility among the Iranian population.A total of 143 men with CAD and 145 healthy age-sex matched controls underwent genotyping for the - rs7041 and rs4588 polymorphisms using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Serum level of 25(OH)D was assayed using microplate colorimetric enzyme immunoassay.We found a significant association between GG genotype (rs7041) and CAD (p=0.02, OR=0.537 95% CI =0.306-0.944). Regarding rs4588 polymorphism, a significant difference was observed in which the CA genotype (p=0.00032, OR=2.578, 95% CI=1.579-4.208) and allele A (P=0.028, OR=1.491, 95% CI=1.043-2.132) were significantly higher in CAD patients compared to controls. In spite of lower serum levels of 25(OH)D in CAD patients, we found no significant association between these SNPs and Vitamin D serum concentrations.We concluded that VDBP polymorphisms affect the susceptibility to CAD in Iranian men. Therefore, further studies are required to clarify the association of VDBP phenotypes and its serum levels with CAD.Koronarna arterijska bolest (CAD) jedno je od najrasprostranjenijih hroničnih oboljenja. Vitamin D-vezuju}i protein (VDBP) i njegovi genetski polimorfizmi predočeni su kao podložne komponente za CAD. Cilj ove studije bio je da se ispita povezanost između polimorfizama pojedinačnih nukleotida (SNPs) proteina VDBP –rs7041 i rs4588 i podložnosti CAD u populaciji Iranaca.Ukupno 143 muškarca sa CAD i 145 zdravih kontrolnih ispitanika odgovarajućeg uzrasta i pola podvrgnuto je genotipizaciji za polimorfizme –rs7041 i rs4588 pomoću metode lančane reakcije polimeraze odnosno polimorfizama dužine restrikcionih fragmenata (PCR-RFLP). Nivo 25(OH)D u serumu određen je pomoću kolorimetrijskog enzimskog imunoeseja na mikroploči.Otkrili smo značajnu povezanost između genotipa GG (rs7041) i CAD (p=0,02, OR=0,537 95% CI=0,306– 0,944). [to se tiče polimorfizma rs4588, uočena je značajna razlika, pri ~emu su genotip CA (P=0,00032, OR=2,578, 95% CI=1,579–4,208) i alel A (P=0,028, OR=1,491, 95% CI=1,043–2,132) bili značajno viši kod obolelih od CAD u poređenju s kontrolom. Uprkos nižim serumskim nivoima 25(OH)D kod pacijenata sa CAD, nije otkrivena značajna povezanost između ovih polimorfizama i koncentracija vitamina D u serumu.Zaključili smo da polimorfizmi VDBP utiču na podložnost CAD kod iranskih muškaraca. Dakle, potrebne su dalje studije kako bi se razjasnila povezanost između fenotipova VDBP i njegovih nivoa u serumu i CAD.

Release of nucleophosmin (NPM) from nucleoli following stress promotes rapid stabilization of the tumor suppressor p53 (TP53, best known as p53). Nucleoplasmic NPM binds to the ubiquitin ligase mouse double minute 2 (MDM2) and prevents MDM2-dependent p53 degradation. We recently demonstrated that sirtuin 7 (SIRT7) activates this pathway by directly deacetylating NPM following ultraviolet irradiation, indicating tumor-suppressive functions of SIRT7.

Recent genome-wide association studies (GWAS) identified a list of single-nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD). Replication of GWAS findings in different population corroborated the observed association in the parent GWAS. In this study, we aimed to replicate the association of rs1870634, a GWAS identified SNP, to CAD in an Iranian population. The study population consisted of 267 subjects undergoing coronary angiography coronary angiography including 155 CAD patients and 112 non-CAD age- and gender-matched controls. The genotype determination of rs1870634 SNP performed using high-resolution melting analysis (HRM) technique. Our results revealed that the GG genotype frequency was significantly higher in CAD patients compared with controls (P = 0.03). The results of binary logistic regression suggested that this genotype was significantly associated with CAD risk adjustment for age, BMI, sex, TC, and LDL-C lipid levels (OR of 2.78, 95% CI (1.10–7.01), P = 0.03). Moreover, our results showed that the GG+TG genotypes were 2.52 times more likely to develop CAD (95% CI 1.05–6.03) than TT genotype carriers after adjusting for age, sex, and lipid profiles (P = 0.037). These data showed that the GG genotype could be associated with increased risk of CAD in a sample of Iranian population.