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Introduction: Angiotensin Converting Enzyme or ACE is an exopeptidase that causes the conversion of angiotensin I to angiotensin II, vasoconstriction, and aldosterone secretion. ACE gene polymorphism (I/D) causes more enzyme activity and increases the risk of coronary artery disease or CAD. Aims: To examine the role of ACE (I/D) Gene Polymorphisms by Stent Types (Biomime, Supraflex, Xience) has been investigated in patients who underwent angioplasty in this study. Material & Methods: Patients in the in-stent restenosis group (ISR+) (N=53) and patients non-ISR group (ISR-) (N=68) have been enrolled in this study based on follow-up angiography > 1 year after PCI. Frequencies of allele and genotypes of the ACE (I/D) variant were determined using polymerase chain reaction (PCR). Results: The genotypes and allele frequencies were not significantly different between the studied populations (p-Values > 0.05). However, there was a significant difference between people with a history of Clopidogrel use in the ISR- and ISR+ groups observed (p-Values > 0.005). Conclusion: In the present study, there was no statistically significant relationship between ACE (I/D) gene polymorphism and the incidence of restenosis in patients who underwent repeat angiography. However, the ratio of frequency percentage of alleles to each other in terms of frequency shows the highest to lowest alleles I/D, D/D, and I/I in both groups. In the comparison of drugs used among patients, the drug Clopidogrel (Plavix) is discussed in the incidence of restenosis, in this study, the results showed that the number of patients who received Clopidogrel in the ISR+ group was significantly less than the ISR- group. This issue can indicate the inhibitory effect of Clopidogrel in the recurrence of stenosis.

Objectives Maturity-onset diabetes of the young (MODY), an autosomal dominant disease, is frequently misdiagnosed as type 1 or 2 diabetes. Molecular diagnosis is essential to distinguish them. This study was done to investigate the prevalence of MODY subtypes and patients’ clinical characteristics. Methods A total of 43 out of 230 individuals with diabetes were selected based on the age of diagnosis >6 months, family history of diabetes, absence of marked obesity, and measurable C-peptide. Next-generation and direct SANGER sequencing was performed to screen MODY-related mutations. The variants were interpreted using the Genome Aggregation Database (genomAD), Clinical Variation (ClinVar), and pathogenicity prediction tools. Results There were 23 males (53.5%), and the mean age at diabetes diagnosis was 6.7 ± 3.6 years. Sixteen heterozygote single nucleotide variations (SNVs) from 14 patients (14/230, 6%) were detected, frequently GCK (37.5%) and BLK (18.7%). Two novel variants were identified in HNF4A and ABCC8. Half of the detected variants were categorized as likely pathogenic. Most prediction tools predicted Ser28Cys in HNF4A as benign and Tyr123Phe in ABCC8 as a pathogenic SNV. Six cases (42.8%) with positive MODY SNVs had islet autoantibodies. At diagnosis, age, HbA1c, and C-peptide level were similar between SNV-positive and negative patients. Conclusions This is the first study investigating 14 variants of MODY in Iran. The results recommend genetic screening for MODY in individuals with unusual type 1 or 2 diabetes even without family history. Treatment modifies depending on the type of patients’ MODY and is associated with the quality of life.

Multiple Sclerosis (MS) is a chronic and autoimmune disease of the central nervous system that causes inflammation in the brain and spinal cord, progressive degeneration of central nervous system tissue, damage to neuronal axons, and loss of function of central nervous system neurons. Experimental encephalomyelitis is an alternative animal model of MS that can simulate the symptoms of this disease. Cuprizone is one of the factors creating this model. Various researchers are testing the use of different cells to reduce the symptoms of cuprizone-demyelinated mice. The different injection methods explained in this article include intracerebral, intraperitoneal, intravenous, and intranasal. The intracerebral method, in contrast to the intranasal method, was widely employed by researchers. In each technique, the researchers try to inject a specific type of stem cell (SC) and monitor their efficiency. For monitoring SCs various labeling procedures are available, however, there is an upward trend in using magnetic resonance imaging (MRI). Two main barriers to using this method are high cost and complexity. In the current review, we try to make review cell therapy in the cuprizone model of MS.

Approximately 80% of prelingual deafness is caused by genetic mutations and follows an autosomal recessive inheritance pattern. Over 6000 variants in almost 110 genes have been identified in nonsyndromic hearing loss so far. In this study, we investigated the genetic cause of nonsyndromic hearing loss in an Iranian young woman using whole exome sequencing (WES) and performed segregation analysis. We detected a homozygous single base insertion (c.904_905insA, p.Ile302Asnfs) in exon eight of GPSM2 gene causing a change in the reading frame. This mutation was also confirmed in homozygous and heterozygous forms in the affected sibling and parents, respectively. Based on the segregation analysis we performed, individuals harboring c.904_905insA mutation in homozygous form are affected by nonsyndromic hearing loss.

Background: Cancer stem cells (CSCs) are a small subpopulation of cells within tumors and play significant roles in tumorigenesis, metastasis, resistance to treatment, and relapse. They are defined by self-renewal and multi-lineage differentiation, and aggressiveness. Epigenetic modifications, including DNA methylation and acetylation, histone modifications, and non-coding. RNAs (ncRNAs), are partly responsible for CSC potentials and are involved in the modification of key components of crucial pathways such as Notch and Wnt signaling in breast cancer. Objective: In this review, we present an overview of the pathways and epigenetic events that lead to the transformation of mammary gland stem cells to breast CSCs (BCSCs). Based on the data presented here, important pathways such as TGF-β/SMAD2 and Wnt/β-catenin and epigenetic modifications, including histone modifications, DNA methylations, and microRNAs, play important roles in BCSC formation and maintenance. Conclusion: Epigenetic events can alter the expression of genes and functional RNAs, resulting in tumor initiation and progression. Thus, a better understanding of epigenetic modifications involved in BCSC maintenance signaling pathways may help to eliminate or suppress BCSCs and overcome cancer by generating more effective and efficient therapeutic agents.

In this review, we focus on the application of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated nuclease 9 (Cas9), as a powerful genome editing system, in the identification of resistance mechanisms and in overcoming drug resistance in the most frequent solid tumors.Data were collected by conducting systematic searching of scientific English literature using specific keywords such as "cancer", "CRISPR" and related combinations.The review findings revealed the importance of CRISPR/Cas9 system in understanding drug resistance mechanisms and identification of resistance-related genes such as PBRM1, SLFN11 and ATPE1 in different cancers. We also provided an overview of genes, including RSF1, CDK5, and SGOL1, whose disruption can synergize with the currently available drugs such as paclitaxel and sorafenib.The data suggest CRISPR/Cas9 system as a useful tool in elucidating the molecular basis of drug resistance and improving clinical outcomes. Graphical abstract The mechanisms of CRISPR/Cas9-mediated genome editing and double-strand breaks (DSBs) repair.

Human semen contains several trace elements such as calcium (Ca), copper (Cu), manganese (Mn), magnesium (Mg), zinc (Zn) and selenium (Se) which are necessary for reproductive health, normal spermatogenesis, sperm maturation, motility and capacitation, as well as normal sperm function. In this review, the potential role of these trace elements in male reproductive health, normal function of spermatozoa and fertility potency were considered. We selected and reviewed articles that considered crucial roles of trace elements in human sperm function and fertility. Ca is essential for sperm motility and its hyperactivation, sperm capacitation and acrosome reaction, as well as sperm chemotaxis. Sodium (Na) and potassium (K) are involved in sperm motility and capacitation. Mg is necessary for normal ejaculation, spermatogenesis and sperm motility. Zn is one of the most significant nutrients in human semen. Seminal deficiency of Zn can be associated with delayed testicular development, impaired spermatogenesis, deficiency of sex hormones, oxidative stress and inflammation, and apoptosis. Se is another significant element which has antioxidative properties and is essential for spermatogenesis and the maintenance of male fertility. Mn is a potent stimulator for sperm motility; however, increased level of seminal plasma Se can be toxic for sperm. Like Se, Cu has antioxidative properties and has a positive effect on sperm parameters. Decreased level of these trace elements can negatively affect human reproductive health, semen quality, sperm normal function and as the result, fertility potency in men. Measurement of these trace elements in men with idiopathic infertility is necessary.

This study aimed to consider the expression of Nrf2, NLRP3 and caspase 1 genes, as well as oxidative stress, and the protective role of N-acetyl cysteine (NAC) in the liver of rats treated with cadmium (Cd). Male rats were randomly divided into five groups including G1 (control), G2 (single dose of Cd), G3 (continuous dose of Cd), G4 (single dose of Cd + NAC), and G5 (continuous dose of Cd + NAC). Levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured. Expression of Nrf2, NLRP3 and caspase 1 genes was considered using RT-PCR. NAC treatments significantly improved TAC, but decreased MDA values in rats that exposed to continuous dose of Cd (p

Congenital Leptin receptor (LEPR) deficiency is a rare genetic cause of early-onset morbid obesity characterised by severe early onset obesity, major hyperphagia, hypogonadotropic hypogonadism and immune and neuroendocrine/metabolic dysfunction. We identified a homozygous loss-of-function mutation, NM_002303.5:c.464 T > G; p.(Tyr155*), in the LEPR in an extended consanguineous family with multiple individuals affected by early-onset severe obesity and hyperphagia. Interestingly, the LEPR-deficient adult females have extremely high body mass index (BMI) with hypogonadal infertility, the BMI of the affected males began to decline around the onset of puberty (13–15 years) with fertility being preserved. These findings lead to the speculation that LEPR deficiency may have a gender-specific effect on the regulation of body weight. In order to elucidate gender-specific effects of LEPR deficiency on reproduction further investigations are needed. The limitations of this study are that our conclusion is based on observations of two males and two females. Further LEPR deficient males and females are required for comparison in order to support this finding more confidently.