Personalized and Precision Medicine Journal

Abstract Renal Cell Carcinomas (RCC) are a wide range of heterogeneous tumors that mainly originate in renal tubular epithelial cells. These carcinomas are more common in males older than 60. Studies have shown that overexpression of the Long Non-Coding RNA (lncRNA) TCL6, which is a lncRNA with roles in T-cell lymphoproliferative diseases, could suppress the proliferation and growth of Clear Cell RCC (ccRCC) cells. The present study intended to investigate the association of this specific lncRNA with ccRCC by comparing the expression levels in cancerous tissues with the adjacent normal tissues.
The study included 44 samples of ccRCC cells and healthy, adjacent tissue from the affected patients. The expression levels of TCL6 lncRNA were assessed in the cancerous tissues and the adjacent normal tissues using real-time PCR.
According to the results, TCL6 lncRNA was significantly underexpressed in the cancerous tissues than the adjacent normal tissues.
In conclusion, these findings indicated that TCL6 might have roles in the tumorigenesis regulation and development of RCC.

Abstract Introduction: In this study, we evaluated the Seroepidemiology of T. gondii among470 pregnant women as well as association of infection with socio-demographic factors and risk factors such as age, and education was studied, which makes it a potential therapeutic option for personalized medicine. Methods: This cross sectional study was conducted among 470 pregnant women who presented to health centers from February 2013 to January 2014. Serum samples were prepared via a commercial ELISA kit (Euroimmun, Germany) for the attendance of IgG and IgM toxoplasma antibodies and the avidity of the IgG antibody based on the manufacturer’s protocol. Results: We found 34.4% of Toxoplasma IgG. Among 470 pregnant women, 166 cases positive for IgG antibodies toxoplasma were detected, showing a serum incidence of 35.31% (95% confidence interval 27.8 to 37.06%),and thirty eight (22.89%) out of 166 IgG-positive women revealed specific IgM antibodies. Conclusions: Our data showed that the prevalence of T. gondii infection is not related to age, gestational age, number of pregnancies, history of abortion, contact with soil, life in rural areas and education related to infection. as well as these findings may be of major interest for the select of the first-line anti-infection drug, and the urgent require for developing personalized medicine.

Abstract Objectives: Diabetes mellitus type 1 (T1DM), which is also an autoimmune disorder, can coexist alongside other types of autoimmune diseases. This study aimed to investigate the possibility of a subclinical association between diabetes disease and autoimmune thyroid dysfunction. The clinical condition of the patient and their approach to managing their diabetes were specifically considered when deciding whether or not the patient had autoantibodies.
Methods: This study included sixty individuals who were diagnosed with diabetes type 1. (thirty males and thirty women, with a mean age of 21.04 years) and 30 healthy controls (12 males and 18 females).
Results: Diabetics had considerably greater serum IL-10, IL-6, and TNF-α levels than healthy controls. Stepwise regression indicated significant positive correlations between IL-10, IL-6, and TNF-α with these antibodies and strong inversed relationships between IL-6 and Anti-TPO, Anti-TG, antibodies.
. No matter if the antibodies were present or how severe they were, this held true. The study's findings lend credence to the idea that people with type 1 diabetes should have their thyroid antibodies and function checked.
Conclusions: Thyroid antibodies were most common among type 1 diabetics aged 21–35, according to our study (Anti-TPO and Anti-TG). IL-10, IL-6, and TNF-α levels in diabetic patients and controls were significantly different (P<0.01). IL-10, TNF-α, HbA1C, and body mass index positively correlated with thyroid antibodies, except for IL-6. Thyroid antibodies and functional abnormalities should be tested often in type 1 diabetics due to the high occurrence of thyroid autoimmune illnesses.

Abstract Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), depicted by lymphocytic infiltration and demyelination. MS is associated with the up-regulation of pro-inflammatory and down-regulation of anti-inflammatory cytokines. The purpose of this experimental study was to evaluate the expression level of TGF-β1, TGF-β 2, TGF-β-R1, and TGF-β-R2 mRNAs in peripheral blood mononuclear cells (PBMCs) from MS patients and healthy controls using Real-Time PCR. Our findings indicated that the TGF-β-R1 expression level was 2.25 times higher in controls than in MS patients. Also, a significant correlation between normalized expression of TGF-β-R1 and TGF-β1, or TGF-β2 was observed. Therefore, these genes could likely play an important role in the etiology of MS.

Abstract Background: Leishmania Species produced diseases include clinical problems from cutaneous self-limiting to severe non-healing forms such as visceral leishmaniasis (VL). As an obligatory intracellular parasite these pathogens proliferate and survive inside macrophages in animals and human; while these cells as a major host immune cell destroy majority of disease producing agents. Because macrophages act as first line of innate immunity, produce several molecules when activated. Proinflammatory and inflammatory cytokines are produced by these cells through their activation, act as main coordinators of the immune system against pathogens and other harmful disease producing factors against the body. Through such a mechanism the immune response resolves the problem.  To play such a critical role many cells as monocytes, macrophages, DCs and others involved in T cell regulation to establish proper innate and adaptive immunity responses. Proinflammatory and inflammatory cytokines are produced in a network acting through many signal pathways.
Methods: In this descriptive designed study, quality-controlled cDNA samples sequenced (RNA-seq) and mapped against a standard human genome version. Results: Based on the results of this study, proinflammatory and inflammatory gene expressions were significantly upregulated.
Conclusion: Upregulations of proinflammatory and inflammatory gene expressions early infection time might be indication for an early  innate immunity response.

Abstract Diabetes Mellitus is defined as a metabolic disorder characterized by chronic hyperglycemia. The more prevalent form, type 2 diabetes, usually begins as insulin resistance, a disorder in which the cells do not use insulin properly. T2DM is a complex multifactorial disease in which multiple genetic variants interact with environmental factors to trigger the disease. There is sufficient evidence that T2DM has a strong genetic basis. One of the identified candidate genes associated with type 2 diabetes is CDKAL1, reduced expression of CDKAL1 would result in enhanced activity of CDK5 in β cells, which would lead to decreased insulin secretion. In this study, the association of polymorphism rs10946398 of CDKAL1 with type 2 diabetes was evaluated in 200 people by RFLP-PCR method. No significant association was found between the genotypes of polymorphism rs10946398 and type 2 diabetes in the target population. It is suggested that this polymorphism association with type 2 diabetes in larger populations evaluated.

Abstract Diabetes mellitus (DM) is a major public health issue in worldwide. Type 2 diabetes does not have a clear pattern of inheritance, although many affected individuals have at least one close family member, such as a parent or sibling, with the disease. The KCNJ11 gene is a member of the potassium channel gene family. polymorphisms  in KCNJ11  result  in  neonatal  diabetes and congenital hyper-insulinaemia, wherein the E23K (rs5219) polymorphism is linked with diabetes susceptibility where the K allele plays an important role in insulin secretion. In this study, we evaluate the frequency of these polymorphisms in a Kurdish population of 85 with type 2 diabetes. E23K polymorphism of KCNJ11 gene was genotyped by PCR-RFLP method. heterozygous carriers for AG are more in non‑diabetic patients (P = 0.034).

Abstract Salmonella is a group of Gram-negative rod shaped bacteria belongs to the Enterobacteriaceae family, 2,500 serotypes have been defined for Salmonella, are associated with 1.3 billion cases of gastroenteritis and 3 million deaths worldwide. For diagnosis of Salmonella spp. 100 vegetable samples was collected from four types of green leaves (Arugula, Leek, Celery and Cress) during February to April 2018, and then examined by cultural method using tow enrichment broth,. Afterward, Salmonella spp. were detected by PCR using Inv-A gene (796 bps). In this investigation, microbiological methods and molecular methods had been used for the diagnosis of Salmonella spp. Combination of both methods confirmed contamination of thirty samples which showed abnormal range for the contamination of vegetables in Erbil province. The present study concluded that both traditional and molecular based techniques like PCR are complementary. In this study, PCR study was carried out to determine the prevalence of Salmonella spp. at the level of Inv-A gene from vegetables, where microbiological findings were combined with the PCR results.

Abstract Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is characterized by high blood sugar, insulin resistance, and relative lack of insulin.Diabetic retinopathy, a secondary microvascular complication of diabetes mellitus, is the leading cause of blindness. There is extensive evidence that the pathologic ocular angiogenesis in diabetic retinopathy is regulated by the vascular endothelial growth factor-A (VEGF-A).The single nucleotide polymorphism (SNP) C936T (rs3025039) of the VEGF gene has been investigated in relation to cancer, endometriosis, and age-related macular degeneration. The relationship between the rs3025039 VEGF gene polymorphism and the risk of type 2 diabetic retinopathy in 80 DT2 patients was examined. No significant association was found between polymorphism C936T and type 2 diabetes. It is recommended that this study be repeated on a larger population.

Abstract Hesperidin is a flavanone present in citrus fruits, such as oranges and lemons. It exerts non-toxic activities in normal cells; however, it has been reported to suppress cell proliferation in several cancer types. Moreover, it was shown that dietary hesperidin acts as an anti-carcinogenic agent for some tumors. In the present study, we investigated the effect of hesperidin on breast cancer cell line MCF7 and also its effects on the expression of apoptosis-related genes in this cell line.
MCF7 cells were divided into 4 groups, including 3 study groups and 1 control group. Each study group was treated with 50, 75, or 100 μg/mL hesperidin, while the control group was left untreated. The samples underwent real-time PCR using the primers specific for BCL-2 and BAX, as the study genes, while GAPDH was used as the control.
According to our findings, hesperidin caused a significant decrease in BCL-2 mRNA levels at all the doses used in the study groups compared to the control group (p < 0.002). The observed decrease was dose-dependent. Also, hesperidin induced a significant overexpression of BAX when used in doses of 75 and 100 µg/mL in comparison to the control group.
The present study proved the significant apoptosis-inducing effect of hesperidin on the breast cancer cell line MCF7.

Abstract Introduction: One of the possibilities is the utilize of personalized medicine, a method based on quantifiable and theoretical agents that assign the worldwide immunological hazard of refusal for each patient. Kidney transplantation is the best treatment for end-stage renal disease patients. Although the shortage of kidneys for transplantation has been addressed by expanding the criteria, transplantation teams in Iran don’t have great tendency to implant marginal organs from brain death donors specially the ones with high creatinine before harvesting. The aim of this study was to evaluate the impact of brain dead donor serum creatinine (Cr) level on outcome of transplanted kidneys. Methods: In this retrospective study, the records of 46 brain-dead donors of Masih Daneshvari organ procurement unit of Tehran, Iran were assessed. The medical file of donated 58 recipients was available. Donor demographic data (age, sex), brain death cause and the Cr level after transferring to OPU ICU were recorded. The Cr level was categorized based on ≥1.4 mg/dl with origin of prerenal azotemia or lower. The urine output of transplanted patients in the first 24 hours post-transplant, serum Cr level at discharge from hospital and dialysis during first month after transplantation were compared between two groups. Results: The mean age of donors was 37yr and 25 (54%) were male. The cause of brain death in 16 (35%) was trauma. The donors’ creatinine level at the admission to the ICU was 1.4mg/dl or higher in 20 (35%). The first 24 hours urine output did not significantly differ between donors’ creatinine level lower than 1.4mg/dl or higher (5500 ± 2678ml and 4068 ± 3399ml, respectively, P=0.083). Similarly the recipient discharge serum Cr level did not significantly differ between two groups (1.69 ± 0.97 and 1.74 ± 1.34 mg/dl, respectively, P=0.887). Overall 8 recipients (14%) needed dialysis during first month after transplantation and there was no significant difference between groups (11% and 20%, respectively, P = 0.320).
Conclusions: Findings of this preliminary study showed that the outcome of transplanted kidneys from brain-dead donors with Cr level >=1.4mg/dl is similar to other patients. So, higher creatinine level is not a good excuse for rejecting the kidneys for transplantation. Because of various confounding factors in the assessment of transplanted kidney outcome, the future studies with larger sample size and longer follow-up period is recommended.

Abstract HCV is a blood pathogen that affects approximately 180 million people worldwide. It has the ability to escape its host’s defense mechanism and is considered a resistant species. Toll-like receptors (TLRs) are a family of evolutionary receptors that have been identified by the diagnosis of pathogens as the main regulators of innate and acquired immune responses. Studies have shown that genetic changes in the TLR3 gene are associated with high susceptibility or resistance to immune and infectious diseases. In this study, the effects of the TLR3 gene single nucleotide polymorphism rs78726532 on susceptibility to HCV infections were examined. The association between this polymorphism and the risk of hepatitis C in 50 patients and 50 healthy subjects was investigated. The results revealed a significant relationship between polymorphism rs78726532 and hepatitis C infection (p = 0.002). Thus, it could have a therapeutic and predictive potential.

Abstract Chemotherapy and radiotherapy adversely affect spermatogenesis, a consequence that is particularly relevant to young men who have yet to establish families. The harmful effects of chemotherapy on spermatogenesis are variable, depending on the type and dosage of chemotherapeutic agents used. The current study assessed the effect of cancer therapy on sperm DNA fragmentation by Comet assay. Sperm DNA fragmentation was evaluated in cured cancer patients. The results showed a significant relationship between chemotherapy and double-stranded and single-stranded sperm DNA fragmentation.
 
 

Abstract Colorectal Cancer (CRC) is the third most common cancer in Iranian men and the fourth most common cancer in women. Recent studies have shown that lncRNAs may also engage in remodeling the tumor microenvironment and tumor metastasis. A lncRNA called LBX2 antisense RNA 1 (LBX2-AS1) has been reported to exert crucial regulatory actions in various cancer. In this study, we evaluate the expression of LBX2-AS1gene in 30 colorectal cancer tumor samples. Gene expression was assessed by Real-time PCR method and the results were analyzed by 2^-DDct. relative expression of this gene in tumor samples compared to healthy samples showed a 1.4-fold increase in tumor samples. According to our findings in this study and the results of other studies, it can be concluded that this gene can be used as a therapeutic target.

Abstract Preimplantation genetic diagnosis is recognized as an effective approach to rule out embryos with abnormal chromosomes in hopes of increasing the chances of a successful pregnancy. The objective of this study is to evaluate the association between types of single cell (blastomere) chromosomal aneuploidy and female partner age using Next Generation Sequencing technique. This study showed that 70.80% of tested samples had abnormal chromosomal complementation, regardless of maternal age or complexity of the abnormality present. 

Abstract Because of their small size, unique physics, and chemical properties, metal nanoparticles can easily cross obstacles and reach their target cells, which makes them an ideal choice for therapeutic purposes in various cancers. In this study, the effects of iron oxide nanoparticles on MDA-MB-231 breast cancer cell line were examined, and biomarkers related to oxidative stress were evaluated. Fe2O3 nanoparticles were suspended in a cell culture medium and diluted to appropriate concentrations (0, 10, 30, 60, and 120 μg/ml) for 24 and 48 h. GSH, superoxide dismutase, catalase, and ROS generation were evaluated. The results showed that iron oxide nanoparticles induced intracellular ROS generation in a dose- and time-dependent manner. The results further showed that iron oxide nanoparticles increased ROS and activated oxidative stress in cells.

Abstract Breast cancer is the most common cancer in women, and its frequency is rising in countries with low and middle incomes. The influence of diet on mammary carcinogenesis has been clearly demonstrated in animal models. Inadequate folate intake has been associated with several cancers, and low levels of serum folate, vitamin B6, and vitamin B12 have been associated with increased breast cancer risk. The levels of folic acid, B6, and B12 in the plasma of 85 people with breast cancer were measured and compared with healthy people. A significant inverse trend was observed between folate intake (p-value=0.004) and vitamin B6 intake (p-value=0.0001) and breast cancer risk. Data from this study suggests that B vitamins, including folate, vitamin B-6, and vitamin B-12, may confer little or no reduction in overall risk of developing breast cancer.

Abstract Background: Lung cancer is the first cause of cancer deaths in the world. Pemetrexed is an antifolate drug used as a first or second-line in the treatment of advanced non-small cell lung cancer (NSCLC) patients. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in a folic acid metabolic pathway and a central role in clinical response to pemetrexed. The aim of this study was to investigate the association between rs1801133 polymorphism and the overall survival of metastatic NSCLC patients.  
Methods: Thirty-four patients with metastatic lung cancer were treated with pemetrexed-based regimen at Rasoul Akram Hospital, Tehran, Iran. Genomic DNA was extracted from the peripheral blood of patients before initiation of treatment. Genotyping of rs1801133 polymorphism was performed at the National Institute of Genetic Engineering by PCR-RFLP methods. Statistical analysis performed with SPSS software, version 21.0.
 Results: Thirty-four patients were enrolled in this study. 21 patients (62%) were male and 13 (38%) were female. The mean age of the patients was 58.90 years. rs1801133 polymorphism were not significantly associated with survival in patients treated with pemetrexed-based chemotherapy.
 Conclusion: Previous studies have demonstrated that MTHFR polymorphism may predict survival among pemetrexed-based regimen treated advanced non-squamous NSCLC patients. However, in this study, the examined polymorphisms were not associated with patients' survival.

Abstract In many cancers, an increase in gene expression of DNMT3b has been reported. This enzyme inhibits the expression of many tumor suppressor genes through the methylation of the promoter sequence and plays a key role in the progression of cancer. In this study, the relationship between polymorphism rs406193 of this gene and the risk of prostate cancer in 60 samples was investigated. The results showed a significant association between genotype TT and the risk of prostate cancer (p=0.048). It is recommended that this study be repeated in larger populations and that the relationship between this polymorphism and gene expression be investigated.

Abstract The goal of precision medicine (PM) is to provide each patient with the treatment and therapy with the optimum  results without significant adverse side effects. PM play an  essential role in patient care as well as therapy because it tailores the medicine on the individual basis, thus decreasing  side effect associated with the drug administration and expediting the treatment as well . Antidepressant drug sertraline (SRT) is currently  prescribed to treat mental disorders. This study aimed to determine how much Ganoderma lucidum protects against SRT-induced testicular damage in mice. Mice were given SRT (at a dosage of 30 mg/kg) orally for 35 consecutive days. For 35 days straight, rats receiving SRT were also given G. lucidum extract (at a dosage of 300 mg/kg). SRT therapy caused immediate testicular injury, as evidenced by the significant degeneration and necrosis of the germ cell lining and an increase in sperm malondialdehyde (MDA) levels. Additionally, evaluation of sperm parameters using computer-assisted sperm analysis (CASA) results demonstrated a substantially lower volume, movement, and survival of sperm in the SRT-treated group (p < 0.001). Administering G. lucidum extracts to animals that had received SRT may have reduced their histological changes. G. lucidum significantly decreased spermatozoa’s lipid peroxidation, and its antioxidant defenses were strengthened. Finally, G. lucidum protects mice›s testicles from harm brought on by SRT, most likely due to its capacity to inhibit reactive oxygen species.

Abstract The miRNAs produced predominantly in the placenta are probably involved in placental differentiation and maintenance of pregnancy. One of the important functions of miR-126 is its involvement in angiogenesis by enhancing the expression of VEGF. Abnormalities of placental vasculature may result in several gestational complications, including pregnancy loss. The current study compared the expression of miR-126 in the plasma of women with recurrent miscarriages and women with healthy pregnancies by Realtime qRT-PCR. The results indicated that the expression difference of miR-21 between the pregnant patients and the controls was statistically significant (p =0.002). This microRNA can be used as a biomarker in diagnosis and progression.

Abstract Uropathogenic Escherichia coli is one of the most important causes of urinary tract infections. These strains possess various virulence factors, including adhesins, toxins, and iron acquisition systems. Virulence genes are situated on mobile genetic elements or in specific regions of the chromosome known as pathogenicity islands. In this study, 375 clinical samples from male and female patients suspected of having urinary tract infections were collected in the hospitals of Dhi Qar, Iraq, during the period from June 1, 2019, to November 1, 2019. Following the collection of 100 samples, bacterial isolation, DNA extraction, and antibiotic sensitivity tests were conducted using the disc diffusion method with the selected antibiotics. The presence of papC, aer, fimH, hly, cnf-1, and afa class genes was investigated using multiplex PCR. The results indicated that the highest frequency among the genes was associated with the fim gene (98%). The aer, papC, cnf-1, hly, and afa genes were also detected, with frequencies of 52%, 30%, 18%, 13%, and 11%, respectively. Additionally, the highest resistance and sensitivity among UPEC isolates were observed for amoxicillin (82.37%) and amikacin (92.35%) antibiotics, respectively.

Abstract Propiconazole is a systemic fungicide from the triazole group used to control a wide range of diseases. This poison causes cellular, genetic and metabolic damage in animals. A bone is a hard tissue whose content is constantly changing. Longitudinal growth of the bone occurs through the growth plate, which is a cartilaginous structure at the end of the body's long bones. During puberty, while the growth plate closes (ossifies), the longitudinal growth of the bone stops. This study aimed to investigate propiconazole's effect on growth plate width changes (including the area of ​​proliferating cells and the area of ​​hypertrophied cells) in immature rats. This experimental study was conducted on 12 immature male Wistar rats randomly divided into control and propiconazole groups. The treatments were done by oral gavage for 28 days. On the 28th day, the dead animals and the left leg femur were separated for histomorphometric studies of the growth plate width of the femoral epiphysis. Investigations were carried out by (Rasband Wayne, 40g.1. ver, ImageJ, USA, NIH), and the significance of the results was done by ANOVA analysis of variance and Tukey's test. The width of the growth plate in the propiconazole group had a significant decrease compared to the control group (P = 0.0126), which is a decrease in the width of the proliferating area (P < 0.001) and an increase in the width of the hypertrophied area (P = 0.016). Propiconazole leads to a decrease in the width of the growth plate of the femoral epiphysis of immature rats. It can be a factor in disrupting the process of longitudinal bone growth and premature closure of the growth plate.

Abstract Chancroid is an STI characterized by the Gram-negative bacteria Haemophilus ducreyi. Controlling chancroid is challenging, and the primary treatment accessible is antimicrobial therapy. However, drug resistance has been seen in places where the disease is common. Due to recent global outbreaks of sexually transmitted infections (STIs), it is crucial to continue researchi ng innovative treatment options and prevention measures. We used reverse vaccinology and subtraction genomic methods to determine potential vaccination and therapeutic targets against H. ducreyi in silico. We found 56 Secreted proteins, with 159 membrane molecules and 515 cytoplasmic proteins. We assessed their need, operation, and ability to cause disease. We identified 6 potential vaccination targets and three pharmacological targets inside pathogenicity islands. The discovered targets may be utilized in future initiatives to manage chancroid globally.

Abstract Obesity and type 2 diabetes are two complex disorders with strong genetic backgrounds, and both disorders cause other diseases and increase mortality. FTO is a protein-coding gene located on the long arm of chromosome 16 and linked to type 2 diabetes and obesity. The current study investigated the relationship between the RS16953002 polymorphism gene and type 2 diabetes and obesity in a population from Tehran. The study population included 150 people with type 2 diabetes and 150 healthy individuals. Genotyping was performed by RFLP-PCR. The results indicated the presence of the GG allele in 81% of diabetic patients but in only64% of non-diabetic participants, which shows a statistically significant difference in this regard. Thus, the current study has shown the role of FTO gene polymorphisms in the pathogenesis of people with type 2 diabetes and obesity.