Mutation Analysis of PAH Gene in Phenylketonuria Patients from the North of Iran: Identification of Three Novel Pathogenic Variants.

Background: There are more than 1100 different pathogenic variants in the phenylalanine hydroxylase (PAH) gene that are responsible for phenylketonuria (PKU) diseases, and the spectrum of these mutations varies in different ethnic groups. The aim of the present study was to identify the frequency of pathogenic variants in all 13 exons of the PAH gene among patients with PKU in Mazandaran and Golestan provinces in the north of Iran. Methods: Forty unrelated PKU patients from Mazandaran and Golestan provinces were enrolled in the study. Genomic DNA was extracted from leukocytes using a Qiagen DNA extraction kit and polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP), and Sanger sequencing methods were applied to detect the variants. In the case of new variants, the InterVar online tool (PMID: 28132688) was used to classify the variants. Results: Twenty-one different pathogenic variants were observed among the 40 investigated patients. The c.106611G>A variant had the highest frequency (27.5%) in the region, and the c.168+5G>C, c.473G>A, and c.782 G>A variants were the other most frequent mutations with allelic frequencies of 7.5, 5, and 5%, respectively. Three novel pathogenic variants including c.773T>G, c.878 T>C, and c. 1245del variants were observed among the investigated patients. Conclusions: The introduction of pathogenic variants in the PAH gene in each ethnic group provides valuable data regarding the understanding of the pathogenesis of the disease and can be helpful for prenatal diagnosis programs.

Hematological parameters in patients with recurrent Aphthous Stomatitis: a systematic review and meta-analysis.

OBJECTIVES: Recurrent Aphthous Stomatitis (RAS) known as recurrent aphthous ulcer is a common and painful ulcerations in oral cavity. It has been suggested that hematological parameters seems to be considered as an etiologic factor. So, this meta-analysis and systematic review was aimed to examine the relationship between RAS and hematological parameters. METHODS: Relevant studies were found using online international databases including Scopus, Science direct, Web of science (ISI), PubMed, and Google Scholar search engine between 2000 and October 2023. The quality of all papers was determined by NOS checklist. Heterogeneity between the results of primary studies was evaluated with I-square index and publication bias was performed by Egger's test and funnel plots. Also, sensitivity analysis was done to check the effect of each of the primary studies on the overall estimate. Also, the statistical analyses were done using Stata software Ver. 11. RESULTS: By combining the results of primary studies, the standardized mean difference (SMD) of vitamin B12, ferritin, folic acid, hemoglobin, iron and zinc indices with a 95% confidence interval (CI) between the case (patients with RAS) and control (Healthy) groups were estimated -0.52(-0.89, -0.14), -0.20(-0.51, 0.11), -0.42(-0.95, 0.11), -0.58(-0.90, -0.27), 0.01(-0.12, 0.15), -0.33(-0.81, 0.14) respectively. The patients with vitamin B12, ferritin, folic acid, and iron deficiencies and reduced hemoglobin (Hb) level reported 2.93(2.28, 3.78), 2.50(1.48, 4.22), 1.51(0.53, 4.29), 1.46(0.70, 3.03), and 2.14(1.38, 3.32), times more susceptible to develop RAS than healthy individuals. CONCLUSION: The results of the meta-analysis indicated that the SMD of vitamin B12 serum and Hb levels in the case group was 52%. Our result have also showed that the odds ratio of vitamin B12, ferritin deficiencies, and decreased Hb level in case group was 2.93, 2.50, and 2.14 times more than healthy group.

A seromolecular study to determine the prevalence of cytomegalovirus in pregnant women referred to health centers in the north of Iran.

Background and Objectives: Because of the controversial aspects of the CMV virus during pregnancy, it should be considered a serious health threat, especially in developing countries. The present seromolecular study aimed to determine cytomegalovirus prevalence in pregnant women referred to health centers in the north of Iran. Materials and Methods: One hundred and twenty-five pregnant women who were referred to health centers in Mazandaran province for regular health checks were randomly selected from Jan 2022 to Oct 2022. To detect the presence of the CMV genome and specific IgM and IgG antibodies against cytomegalovirus, the conventional PCR and ELISA tests were applied respectively. Results: All 125 pregnant women that attended the study were from Mazandaran province with a mean age of 30 years ranging from 20 to 42 years. The result showed that 2 (1.6%), 92 (73.6%), and 2 (1.6%) of the cases were positive for IgM, IgG, and IgM/IgG, respectively. The PCR test results indicated that the CMV DNA was present in 10 (8%) pregnant women. Our study shows that all PCR-positive cases were negative for the IgM test. Of the 10 PCR-positive samples 3 were positive and 1 was suspicious for the IgG test. Conclusion: Our study revealed that there is an urgent need for vaccination or other strategies to prevent and treat congenital CMV infection. Reducing the burden of congenital CMV infection requires global awareness. Further studies are recommended to obtain accurate estimates of the risk of congenital CMV infection.

Coinheritance of the c.-19 G > C and c.315 + 1 G > A Variants in the ß-Globin Gene Leads to Thalassemia Disease: A Report from the North of Iran.

Up to now, more than 300 pathogenic variants have been identified in the ß-globin gene, some of which are categorized as silent mutations that do not change the hematological indices. In the present study, our aim is to introduce the first report of a case with thalassemia intermedia with coinheritance of the c.315 + 1 G > A pathogenic variant and a silent variant (HBB: c.-19 G > C) that was missed during the screening program. Multiplex-Gap-PCR and Sanger sequencing methods were applied to identify α- and ß-globin gene mutations in a 26-year-old male subject with diagnosis of thalassemia. The identified mutations were also checked on the parent's sample. The CBC and capillary electrophoresis tests were performed on the parent's blood samples. The case was compound heterozygote for the c.315 + 1 G > A and c.-19 G > C (rs1239893012) variants. The subject's mother carried the c.-19 G > C variant in the ß-globin gene while her CBC and electrophoresis test results showed a normal pattern. Silent mutations are susceptible to being missed during premarital screening of ß-thalassemia carriers, and the c.-19 G > C variant is recommended to be classified as a pathogenic variant in the ß-globin gene.

Assessment of Hip Range of Motion Limitations in Cases with Low Back Pain Based on the Classified Movement System Impairment.

Background: The hip joint's limitation causes lumbopelvic compensatory motions, accumulating tissue stress on the lumbar spines. It is essential and valuable to evaluate hip rotation range of motion (ROM) in different low back pain (LBP) classifications to understand them and plan the best exercise program. This study aimed to compare hip rotation ROM between subjects with and without LBP classified in movement system impairment (MSI). Materials and Methods: In this cross-sectional study, 100 subjects with LBP were classified into different MSI subgroups (mean age of 41.66 ± 7.82 years), and 100 healthy subjects (mean age of 38.96 ± 8.84 years) participated. Passive and active hip medial and lateral rotations ROM in prone and supine positions for dominant and non-dominant lower limbs were measured. Results: Generally, in the LBP group, minimal lateral rotation as compared to controls in movement tests measuring hip rotation ROM actively and passively, in prone and sitting positions, and for dominant and non-dominant limbs (P < 0.05). There were no significant differences among the LBP subgroups (P > 0.05). Conclusions: Due to LBP, regardless of the MSI categories, remarkably restricted hip lateral rotation ROM.

Beyond steric selectivity of ions using ångström-scale capillaries.

Ion-selective channels play a key role in physiological processes and are used in many technologies. Although biological channels can efficiently separate same-charge ions with similar hydration shells, it remains a challenge to mimic such exquisite selectivity using artificial solid-state channels. Although there are several nanoporous membranes that show high selectivity with respect to certain ions, the underlying mechanisms are based on the hydrated ion size and/or charge. There is a need to rationalize the design of artificial channels to make them capable of selecting between similar-sized same-charge ions, which, in turn, requires an understanding of why and how such selectivity can occur. Here we study ångström-scale artificial channels made by van der Waals assembly, which are comparable in size with typical ions and carry little residual charge on the channel walls. This allows us to exclude the first-order effects of steric- and Coulomb-based exclusion. We show that the studied two-dimensional ångström-scale capillaries can distinguish between same-charge ions with similar hydrated diameters. The selectivity is attributed to different positions occupied by ions within the layered structure of nanoconfined water, which depend on the ion-core size and differ for anions and cations. The revealed mechanism points at the possibilities of ion separation beyond simple steric sieving.

First report of novel mutation (c.790del) on SQSTM1 gene on a family with childhood onset of progressive cerebellar ataxia with vertical gaze palsy.

SQSTM1 gene encodes a protein called p62 that acts as an autophagy receptor in the degradation of protein molecules. A homozygous deletion variant that changes the frame shift in the SQSTM1 gene named c.790 Del A .T was detected in case childhood onset and progressive neurodegeneration with ataxia, and gaze palsy.

Enhance VR: A Multisensory Approach to Cognitive Training and Monitoring.

Cognitive training systems aim to improve specific domains or global cognition by engaging users in cognitively demanding tasks. While screen-based applications can improve performance in the trained cognitive abilities, they are often criticized for their poor transferability to activities of daily living. These systems, however, exclude the user's body and motor skills, which invariably serves to restrict the user experience. Immersive Virtual Reality (IVR) systems, in contrast, present the user with body-related information, such as proprioceptive and visuomotor information, allowing for an immersive and embodied experience of the environment. This feature renders VR a very appealing tool for cognitive training and neurorehabilitation applications. We present Enhance VR, an IVR-based cognitive training and monitoring application that offers short daily cognitive workouts. The games are designed to train and monitor specific cognitive domains such as memory, task flexibility, information processing, orientation, attention, problem-solving, and motor control. The aim is to test whether cognitively demanding tasks, presented in an IVR setting, provide a naturalistic system to train and monitor cognitive capabilities.

The synergistic effects of zinc oxide nanoparticles and fennel essential oil on physicochemical, mechanical, and antibacterial properties of potato starch films.

The purpose of this study was to evaluate the effects of a combination of zinc oxide (ZnO-N) nanoparticles and fennel essential oil (FEO) on the functional and antimicrobial properties of potato starch films. Films based on potato starch containing a combination of ZnO-N (1, 3, and 5%(w/w)) and FEO (1, 2, and 3% (w/w)) produced by casting method and water solubility, water absorption capacity (WAC), barrier properties, mechanical properties, color indexes, and antimicrobial activity of the films against Staphylococcus aureus, Escherichia coli, and Aspergillus flavus were studied. The combination of ZnO-N and FEO had a significant decreasing effect on solubility, WAC, water vapor and oxygen permeability, elongation, and L* index. These additives had an increasing impact on tensile strength, Yang's modulus, and a* and b* indexes (p < .05). By increasing the concentration of ZnO-N and FEO, the antimicrobial activities of bionanocomposite films significantly increased (p < .05). Both ZnO-N and FEO had a significant effect in this respect, although the effects of ZnO-N were more significant. In conclusion, an excellent synergistic effect of ZnO-N and FEO was observed in potato starch films.

Abnormal in-plane permittivity and ferroelectricity of confined water: From sub-nanometer channels to bulk.

Dielectric properties of nano-confined water are important in several areas of science, i.e., it is relevant in the dielectric double layer that exists in practically all heterogeneous fluid-based systems. Molecular dynamics simulations are used to predict the in-plane dielectric properties of confined water in planar channels of width ranging from sub-nanometer to bulk. Because of suppressed rotational degrees of freedom near the confining walls, the dipole of the water molecules tends to be aligned parallel to the walls, which results in a strongly enhanced in-plane dielectric constant (ε∥) reaching values of about 120 for channels with height 8 Å < h < 10 Å. With the increase in the width of the channel, we predict that ε∥ decreases nonlinearly and reaches the bulk value for h > 70 Å. A stratified continuum model is proposed that reproduces the h > 10 Å dependence of ε∥. For sub-nanometer height channels, abnormal behavior of ε∥ is found with two orders of magnitude reduction of ε∥ around h ∼ 7.5 Å, which is attributed to the formation of a particular ice phase that exhibits long-time (∼µs) stable ferroelectricity. This is of particular importance for the understanding of the influence of confined water on the functioning of biological systems.

Abnormal Dielectric Constant of Nanoconfined Water between Graphene Layers in the Presence of Salt.

Ultra-low dielectric constant of nanoconfined water between two flat slabs is a subject of recent experimental and theoretical research. The impact of dissolution of sodium chloride (NaCl) with various concentrations on the dielectric properties of nanoconfined water between graphene layers are investigated using molecular dynamics simulations. We found that, with increasing salt concentration, (i) the out-of-plane dielectric constant increases and (ii) the in-plane dielectric constant decreases non-linearly. Surprisingly, for channels with heights 6.8Å < h < 8 Å, we found an abnormal increase in the in-plane dielectric constant versus salt concentration, which can be linked to the formation of 2D-ice-like structure. This study sheds light on the variation of dielectric properties of nanoconfined water between graphene layers in the presence of salt, which is of importance in ion transport and electrochemical energy storage.

Effects of nano-chitosan coatings incorporating with free /nano-encapsulated cumin (Cuminum cyminum L.) essential oil on quality characteristics of sardine fillet.

Nowadays, adding biological compounds to food packaging is one of the types of active packaging. The aim of this study was to prepare a new degradable coating with free and nano-encapsulated Cumino cyminum L. essential oil (CCEO) with nanochitosan (Nch) base to evaluate the microbial, chemical and sensory properties of sardine fillet samples for 16 days at 4 °C. Nanoliposome using different soy lecithin ratios and cholesterol concentrations (60:0, 50:10, 40:20, and 30:30) and technique of thin-film hydration-sonication, were prepared with a range of 140-164 nm size. Encapsulation efficiency (EE) and distribution of nanoliposomes size were calculated 0.80-0.90 and 49.85-73.01% respectively. To coat sardine fillet samples, nanoliposomes with the lower size of droplet and higher EE percent were selected. The outcomes indicated that coating treatments can effectively inhibit microbial growth and chemical spoilage reflected at lower pH, peroxide value (PV) and thiobarbituric acid reactive substances (TBARs) (P < 0.05). In fact, the results of chemical and microbiological characteristics showed that the samples treated with nanocitosan/nano essential oil (NEO) showed the lowest value among other treatments during the experimental period, in the following, Nch-EO, Nch and control. pH, PV, TBARs, total viable counts (TVC), total pseudomonads count (TPC), and lactic acid bacteria (LAB) were 6.85, 0.03 (mg MDA/kg), 5.23 (mEq/kg), 3.67 (CFU/g), 3.47 (CFU/g), and 4.7 (CFU/g), respectively for Nch-NEO at the end of storage time. In addition, during the experimental period, the highest sensory properties were obtained for the Nch-NEO group. Encapsulation of CCEO reduces the rate of diffusion, thus increasing antimicrobial and antioxidant activity, as well as improving sensory properties. According to the results of this study, CCEO-encapsulated nanochitosan coatings can be used as a potent coating to increase sardine shelf life.

First report of c.425-1G>A mutation in ornithine aminotransferase gene causing gyrate atrophy of the choroid and retina with hyperornithinemia.

BACKGROUND: Gyrate atrophy is a rare autosomal recessive inherited genetic disease. Progressive deterioration of peripheral night vision and blindness are the foremost clinical manifestations of the disease caused by mutations of ornithine aminotransferase gene. CASE: The presented case was an 18-year-old male referred for a progressive reduction of visual acuity, which started when the subject was 7 years old, blurred vision, and hypotonic muscles. OBSERVATIONS: The findings by liquid chromatography with tandem mass spectrometry and high-performance liquid chromatography methods exhibited a high level of ornithine: 248 µmol/L (reference range: 44-206 µmol/L) and 818 µmol/L (reference: 25-123 µmol/L), respectively. After genetic counseling and conducting further investigation, a novel mutation (c.425-1G>A) in ornithine aminotransferase gene was recognized through whole exome sequencing and the mutation was verified using Sanger sequencing method, which is associated with gyrate atrophy phenotype. CONCLUSION: The exact mechanism of chorioretinal atrophy in hyperornithinemia is not known but the increased ornithine level is the clinical manifestation of gyrate atrophy of choroid and retina, muscle weakness, moderate mental retardation, and low cerebral creatine. Pathogenic variant in the ornithine aminotransferase gene associated with gyrate atrophy, may be beneficial as a biomarker to initial diagnosis and treatment of gyrate atrophy disease.

Hydration effects and negative dielectric constant of nano-confined water between cation intercalated MXenes.

Using electrochemical methods a profound enhancement of the capacitance of electric double layer capacitor electrodes was reported when water molecules are strongly confined into the two-dimensional slits of titanium carbide MXene nanosheets [A. Sugahara et al., Nat. Commun., 2019, 10, 850]. We study the effects of hydration on the dielectric properties of nanoconfined water and supercapacitance properties of the cation intercalated MXene. A model for the electric double layer capacitor is constructed where water molecules are strongly confined in two-dimensional slits of MXene. We report an abnormal dielectric constant and polarization of nano-confined water between MXene layers. We found that by decreasing the ionic radius of the intercalated cations and in a critical hydration shell radius the capacitance of the system increases significantly (≃200 F g-1) which can be interpreted as a negative permittivity. This study builds a bridge between the fundamental understanding of the dielectric properties of nanoconfined water and the capability of using MXene films for supercapacitor technology, and in doing so provides a solid theoretical support for recent experiments.

Evaluation of adverse effects of chemotherapy regimens of 5-fluoropyrimidines derivatives and their association with DPYD polymorphisms in colorectal cancer patients.

BACKGROUND: 5-Fluorouracil (5-FU) and capecitabine are fluoropyrimidine derivatives that mainly metabolized with dihydropyrimidine dehydrogenase enzyme (DPD). The genetic polymorphism in the genes encoding this enzyme may result in a decrease or loss of enzyme activity which may lead to the accumulation of medicines, their metabolites and potential toxicity. METHOD: This cross-sectional study was conducted on 88 participants with colorectal cancer (CRC). After DNA extraction, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the DPD gene (DPYD) polymorphisms including IVS 14 + 1 G > A, 2846 A > T and 2194 G > A. Chemotherapy-induced side effects were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE Version 5.0). RESULT: Data were collected from 227 chemotherapy cycles of 88 patients with CRC. In a comparison of FOLFOX and FOLFIRI regimens, there was no significant difference in the occurrence of chemotherapy-induced diarrhea, nausea, vomiting and oral mucositis. However, the peripheral neuropathy was more frequent in patients who were treated with FOLFOX (P <  0.001) and hair loss was more common in patients who received FOLFIRI regimen (P = 0.048). Incidence of the DPD IVS14 + 1 G > A polymorphism was observed in four patients (5.5%). There was no association between IVS14 + 1 G > A polymorphism and the occurrence of adverse reactions. CONCLUSION: FOLFOX and FOLFIRI were the most common regimens in CRC patients and their toxicity profile was different in some adverse reactions. Prevalence of IVS14 + 1G > A variant was relatively higher than other similar studies. TRIAL REGISTRATION: Approval code; IR.MAZUMS.REC.95.2480.

Investigation of Five Common Mutations on Phenylalanine Hydroxylase Gene of Phenylketonuria Patients from Two Provinces in North of Iran.

BACKGROUND: There are more than 500 different mutations on phenylalanine hydroxylase (PAH) gene that is responsible for phenylketonuria (PKU) diseases and the spectrum of these mutations is varied in different populations. The main clinical manifestation of untreated patients is severe mental retardation. The PAH gene, that is 90 kb long, is consisted of 13 exons and 12 introns. The aim of the present study was to identify the frequency of five common mutations on PAH gene among patients with PKU in Mazandaran and Golestan provinces including c.1066-11G>A, p. R261Q, p. R252W, p. R261X, and c.1200 + 1G>C. METHODS: Forty unrelated PKU patients, that 22 of them, were from Mazandaran and 18 of them from Golestan provinces were enrolled in the study. Genomic DNA was extracted from leukocytes using Qiagen DNA extraction kit and polymerase chain reaction - restriction fragment length polymorphism method was applied to detect five common mutations. RESULTS: Three out of the 5 investigate mutations were identified among the patients. The c.1066-11G>A mutation has the highest frequency (27.5%) among the patients and the frequency of p. R261Q and p. R261X mutations were 3.75 and 1.25%, respectively. In Golestan province, only c.1066-11G>A mutation was observed in investigated alleles. CONCLUSIONS: The high frequency of c.1066-11G>A mutation in Golestan province may be related to genetic drift, founder effect, and consanguinity.

Torque Teno Virus (TTV) Among ß-Thalassemia and Haemodialysis Patients in Mazandaran Province (North of Iran).

Torque Teno virus (TTV) is a transfusion transmitted virus that seems to be involved in several complications such as acute respiratory diseases, liver diseases, AIDS, cancer, and autoimmune reactions. In the present study the frequency of TTV was investigated among ß- thalassemia (BT) and haemodialysis (HD) patients (high risk patients for TTV) in Mazandaran province, Iran. DNA was extracted from the serum of 82 BT and 100 HD patients, and nested PCR method was applied to detect TTV DNA. The aspartate transaminase(AST) and alanine transaminase (ALT) enzyme levels in BT patients were measured using photometric assay. The mean age of BT and HD patients as 23.4±5.4 and 48.8±8.2 years, respectively. 21% of HD and 26.8% of BT patients were infected with TTV, respectively. The frequency of TTV was not significantly different between two groups of patients and there was no significant correlation between sex and TTV infection. The mean AST and ALT levels in TTV positive BT patients was not significantly higher than TTV negative cases. The present study showed that TTV prevalence in BT patients with recurrent blood transfusion was not significantly higher than HD patients. The investigation of TTV prevalence in healthy individuals is recommended to identify if transfusion or dialysis is associated with higher TTV infection. Besides, although TTV infection did not change the AST and ALT enzymes in BT patients, the liver involvement may still exist in these patients.

Identification of ß-globin haplotypes linked to sickle hemoglobin (Hb S) alleles in Mazandaran province, Iran.

Carrier frequency of the ßS allele has been reported to be 0.19% in Mazandaran province, northern Iran. Haplotype analysis of the ßS allele helps trace the origin of its encoded hemoglobin (Hb) variant, Hb S, in a region. The aim of this study was to investigate the haplotypes associated with ßS alleles in Mazandaran province. Capillary electrophoresis was carried out to detect individuals suspected to have a ßS allele(s). DNA analysis (PCR-RFLP) was used for final confirmation. To identify 5' to 3' ß-globin gene cluster haplotypes associated with ßS alleles, family linkage analysis was applied. Six polymorphic sites (HincII 5' to ε, XmnI 5' to Gγ, HindIII in Gγ, HindIII in Aγ, HincII 3' to ψß and AvaII in ß) were investigated using the PCR-RFLP method. Five different haplotypes were linked to ßS alleles, while ßA alleles were associated with nine haplotypes. Among the ßS alleles, 53.9% were associated with the Benin (----++) haplotype, and the Arab-Indian (+++-++) haplotype had the second-highest frequency (23%). Unlike southern provinces, where the Arab-Indian haplotype is prominent, the Benin haplotype is the most frequent haplotype in northern Iran, and this may represent a founder effect. Since the Benin haplotype does not carry the XmnI polymorphism 5' to the Gγ gene, which is responsible for high expression of Hb F, a severe form of sickle cell disease can be anticipated in patients that are homozygous for the ßS allele in the northern region.

Is Vitamin C Supplementation in Patients with ß-Thalassemia Major Beneficial or Detrimental?

Globally, ß-thalassemia major (ß-TM) is one of the most common hereditary disorders. Multiple blood transfusions, that are a life-saving therapy in patients with ß-TM, is a major source of iron overload. Iron overload can lead to significant morbidity and mortality. Research evidence indicates that oxidative stress induced by iron overload, is one of the major precipitating causes of vitamin C deficiency in ß-TM patients. It has previously been shown that patients with ß-TM have significantly lower levels of vitamin C as compared to healthy individuals. It is believed that vitamin C can reduce both ferric (Fe(3+)) and ferrous (Fe(2+)) ions, and also facilitate the accessibility of iron to chelators through increase of iron release from the reticuloendothelial system. Despite the potential benefits of vitamin C in patients with ß-TM, several areas of concern exist that should be addressed by high quality research designs. Some recommendations have been provided through this study.

Potential Effects of Silymarin and Its Flavonolignan Components in Patients with ß-Thalassemia Major: A Comprehensive Review in 2015.

Major ß-thalassemia (ß-TM) is one of the most common inherited hemolytic types of anemia which is caused as a result of absent or reduced synthesis of ß-globin chains of hemoglobin. This defect results in red blood cells lysis and chronic anemia that can be treated by multiple blood transfusions and iron chelation therapy. Without iron chelation therapy, iron overload will cause lots of complications in patients. Antioxidant components play an important role in the treatment of the disease. Silymarin is an antioxidant flavonoid isolated from Silybum marianum plant. In the present study, we reviewed clinical and experimental studies investigating the use of silymarin prior to September 1, 2015, using PubMed, ISI Web of Knowledge, Science Direct, Scopus, Ovid, and Cochrane Library databases and we evaluated the potential effects of silymarin on controlling the complications induced by iron overload in patients with ß-TM. Based on the results of the present study, we can conclude that silymarin may be useful as an adjuvant for improving multiple organ dysfunctions.