Some Notes on Stem Cell Therapy in Cardiovascular Diseases

Cardiovascular diseases have become an increasing clinical issue worldwide. Acute ischaemic injury and chronic cardiomyopathies lead to permanent loss of cardiac tissue and ultimately heart failure. Current therapies widely aim to attenuate the pathological changes that occur after injury and to reduce risk factors of cardiovascular diseases. However, they do not improve the patient's quality of life or the prognosis more than moderate. A new challenge in the treatment of the cardiovascular disease is cellular transplantation or cellular cardiomyoplasty. Different types of stem cells have been used for stem cell therapy. Clinical trials using primary bone-marrow-derived cells and skeletal myoblasts have also shown some encouraging results. An additional clinical and pre-clinical study to further enhance the beneficial effects of cell therapy is necessary. Recent studies have shown that there are various pools of putative resident stem cells in an adult heart, raising the hope that these cells can contribute to the treatment of cardiovascular diseases

Association of polymorphisms in TLR3 and TLR7 genes with susceptibility to COVID-19 among Iranian population: a retrospective case-control study

Background and Objectives: Host genetic changes like single nucleotide polymorphisms (SNPs) are one of the main factors influencing susceptibility to viral infectious diseases. This study aimed to investigate the association between the host SNP of Toll-Like Receptor3 (TLR3) and Toll-Like Receptor7 (TLR7) genes involved in the immune system and susceptibility to COVID-19 in a sample of the Iranian population. Materials and Methods: This retrospective case-control study evaluated 244 hospitalized COVID-19 patients as the case group and 156 suspected COVID-19 patients with mild signs as the control group. The genomic DNA of patients was genotyped for TLR7 (rs179008 and rs179009) and TLR3 (rs3775291 and rs3775296) SNPs using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: A significant association between rs179008 SNP in the TLR7 gene and the susceptibility of COVID-19 was found between case and control groups. The AT genotype (Heterozygous) of TLR7 rs179008 A>T polymorphism showed a significant association with a 2.261-fold increased odds of COVID-19 (P=0.003; adjusted OR: 2.261; 99% CI: 1.117-4.575). In addition, a significant association between TC genotype of TLR7 rs179009 T>C polymorphism and increased odds of COVID-19 (P 0.004167). Conclusion: SNPs in TLR7 rs179008 and rs179009 genotypes are considered host genetic factors that could be influenced individual susceptibility to COVID-19. The SNPs in TLR3 (rs3775296 and rs3775291) showed no significant association with COVID-19 in Iranian population

Study of Fas 1377 G˃A polymorphism in breast cancer of Iranian patients

Background: Apoptosis or programmed cell death is essential for developing and tissue repair. Apoptosis stimulates by binding fas to fas ligand that plays an important role in regulation of the immune system. There are Conflicting data on the association between 1377 polymorphisms and susceptibility to cancer. This study has been conducted to investigation the relationship between polymorphism 1377 A / G in the Fas gene and breast cancer of Iranian patients. Materials and Methods: 65 patients with breast cancer and 57 control subjects were studied. In this study, PCR-RFLP method was used to determine genotypes. Statistical analysis software SPSS 19, by two-dimensional tables X2 test with 99% confidence intervals were calculated . Results: The results were showed that the genotype AA 70.7%, GG 27.7%, AG 1.53% of breast carcinoma samples and genotypes AA 56.1%, GG 17.5%, AG 26.3% prevalence among the controls. Also according to Hardy-Weinberg equilibrium, the frequency of allele A in cancer patients was 71.5% and the frequency of G was 28.5% and the frequency of allele A in control subjects was 69.3% and for allele G 30.7% was calculated. Statistically significant relationship was observed between the two groups. (P-Value ˃0.01) Conclusion: According to the findings of this study, polymorphism 1377 G / A in Fas gene were associated with susceptibility to breast cancer, and it can be considered as a factor in breast carcinogenesis

Path to Personalized Medicine for Type 2 Diabetes Mellitus: Reality and Hope

Type 2 diabetes mellitus (T2DM) is recognized as a public health problem and increasingly prevalent illness. Key elements of the guideline for diabetes care are based on evidence-based medicine approach and apply for population, not individuals. However, individualized care can improve diabetes management. Personalized medicine is otherwise called precision medicine tries to find better prediction, prevention, and intervention for T2DM individuals. Precision medicine in diabetes refers to the utility of genomics data of a patient with diabetes to provide the most effective diagnosis strategies and treatment plans. Over 100 genetic loci influence susceptibility to T2DM. Genomics data together with the potential of other “Omics” and clinical evidence-based data will lead to diabetes care improvement in the context of personalized medicine in the near future. Breakthrough of technologies enables much greater improvements in the understanding of individual variations that may alter the T2DM outcome. This article represents a comprehensive review of current knowledge on the impact of personalized medicine in T2DM

Association between the Asp327Asn Polymorphism of Sex Hormone-Binding Globulin Gene and Prostate Cancer

Background: By binding SHBG hormone to sex hormones, in addition to carrying them in the blood, they regulate the amount of tissue availability. Since the genetic changes in the structure of globulin affect it’s binding to hormones, so in this study the effects of single nucleotide change in exon 8 or rs 6259 in the incidence of prostate cancer is evaluated. Methods: The study population included 120 patients with prostate cancer and 120 control subjects. After collecting blood samples, DNA was extracted by salting out the method in order to determine the genotype of individuals by RFLP-PCR method. According to Hardy-Weinberg equilibrium genotypes and allele frequencies were calculated and a relationship between this variation and prostate cancer were evaluated and by using SPSS 23 software and the relationship between variations. The significance level was considered ≤0.05. Results: Results indicated that homozygous mutant genotype AA 2.58 (p value= 0.007, OR: 2.58, CI95%: 1.52-4.38) and heterozygous AG 1.18 times (p-value =0.5, OR: 1.18, CI95%: 0.38-3.61) increase chance of getting prostate cancer in carriers. But homozygous of wild genotype GG have the protective role against prostate cancer (p-value =0.005, OR: 0.385, CI95%: 0.23-0.65). Conclusion: Therefore, Asn allele is one of the main factors in prostate cancer so it can be used as the non-invasive and suitable marker for early detection in susceptible individuals

Association between Cytochrome P450 2 C9 and Vitamin K Epoxide Reductase Complex Subunit 1 Polymorphisms with Warfarin dose among Iranian Patients

Background: Warfarin is a common anticoagulant drug that has a narrow therapeutic index; higher dose causes excessive bleeding and lower dose leads to cerebrovascular clotting and stroke in patients. Genetic factors that have been associated with warfarin response are the genes of cytochrome P450 2C9 (CYP2C9), which metabolize the more active S-enantiomer of warfarin, and vitamin K epoxide reductase (VKOR), the target site for warfarin. The present study was conducted to investigate the association between CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) polymorphisms with warfarin daily dose on &nbsp;Iranian patients under warfarin treatment. Materials and Methods: This study is comprised of 118 Iranian patients on warfarin treatment who attended the PT Clinic. Genotyping of CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) was performed by PCR-RFLP method. Multiple regression model was performed for statistical analyses and P<0.05 was considered as significance level. Results: The allelic frequencies of CYP2C9*2 and CYP2C9*3 were 19% and 7%, respectively. Patients with &ge;1 CYP2C9 variant allele had a significantly lower mean warfarin daily dose compared with patients with the wild-type genotype. The allelic frequencies of VKORC1 were 14.4%, 57.6% and 27.9% for GG, GA, and AA genotypes, respectively. The mean (SD) warfarin daily dose in patients with the VKORC1 (&ndash;1639) GG genotype was significantly higher than GA and AA patients. Conclusion: CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) polymorphisms had significant association with warfarin daily dose; furthermore, the daily warfarin dose was not influenced by age, height, weight and sex

Genotype–Phenotype Correlations in Iranian Myotonic Dystrophy Type I Patients

Objectives: Myotonic Dystrophy type I (DM1) is a dominantly inherited disorder with a multisystemic pattern affecting skeletal muscle, heart, eye, endocrine and central nervous system. DM1 is associated with the expansion and instability of CTG repeat in the 3' untranslated region of the myotonic dystrophy protein kinase (DMPK) gene located on chromosome 19q13.3. The aim of this study was to determine clinical and genetic characteristic of DM1 in Iranian patients. Genotype-phenotype correlation was also assessed in a small group of studied patients. Methods: Twenty six DM1 patients belonging to seventeen families were analyzed. Clinical assessment was based on the muscular disability rating scale (MDRS) and a sum of symptoms score (SSS). Molecular analysis (PCR and Southern blot) was used to clarify uncertain clinical diagnosis and in order to confirm clinical findings. Results: There was an inverse and significant correlation between age of onset&nbsp; and expanded allele&nbsp; length (P=0.026, tau-b=-0.360) based on Kendall's tau-b correlation coefficient, while there was no significant correlation between age of onset and severity of the clinical symptoms (P<0.05). Also no significant correlation was observed between the two severity scales of the disease (MDRS and SSS) and expanded allele length (P<0.05). Expanded allele length was correlated with hypogonadism (P=0.007) and cognitive impairment (P=0.034). Discussion: There was no correlation between cataract and endocrine dysfunction with the expansion size in DM1 patients. Generally it seems there is discordant correlation between clinical symptoms and expanded allele length

Analysis of the association Hind III Polymorphism of Lipoprotein Lipase gene on the risk of coronary artery disease

Background: Coronary artery disease (CAD) is one of the leading causes of death and disability around the world. Interaction between genetic and environmental factors determines susceptibility of an individual to develop coronary artery disease . Lipoprotein lipase (LPL) play an important role in the metabolism of HDL-C ( High Density Lipoprotein Cholesterol ), LDL-C (Low Density Lipoprotein Cholesterol ) and triglycerides (TG). Dysfunction of LPL as a result of genetic variants of lipoprotein lipase gene is associated with increased risk of CAD. The aim of the present study was to investigate the relationship between the risk of coronary artery disease and LDL-C, HDL-C and TG (triglycerides) levels by lipoprotein lipase gene Hind III polymorphism. Materials and Methods: A total of 202 subjects including 114 patients with coronary artery disease and 88 control participated in this study. The Hind III polymorphism of the lipoprotein lipase gene was determined by PCR- RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) . In the presence and absence of restriction site, the genotypes are described H+/+ , H-/- respectively. Results: In this survey, a highly significant association between the frequent H+/+ genotype and unfavorable TG levels was observed in our population . For the Hind III genotypes, within the healthy subjects (n=88), the H+/+ genotype was found in 67 individuals (58.8%), H-/+ genotype in 38 individuals (33.3%) , and 9 individuals (7.8%) carried the H-/- genotype. Within the CAD group (n=114), 47 individuals (53.4%) with H+/+ genotype, 36 (41%) with H-/+ genotype, and 5 (5.6%) carried the H-/- genotype. Conclusion: There was a significant difference between the distribution of LPL–Hind III genotypes and the healthy subjects and the patients with CAD (P<0.05, 0. 645). LPL–Hind III polymorphisms were not detected as independent risk factors for CAD in this study group, but had significant associations with TG levels (P<0.05)