Personalized and Precision Medicine Journal

Abstract  Autoimmune diseases (AIDs) are characterized by the immune system’s maladaptive response against self-antigens, culminating in chronic inflammation and progressive tissue damage. Although genetic predisposition establishes baseline susceptibility, environmental pollutants—such as heavy metals, pesticides, fine particulate matter (PM2.5), and industrial chemicals—are increasingly recognized as pivotal triggers of immune dysregulation. These xenobiotics induce oxidative stress, disrupt immune tolerance by impairing regulatory T-cell function, and modulate critical signaling pathways including NF-κB, MAPK, and JAK-STAT. Epidemiological studies corroborate associations between pollutant exposure and heightened incidence or severity of conditions such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes. This review synthesizes molecular, cellular, and population-based evidence to elucidate the mechanisms by which environmental pollution contributes to the onset and progression of AIDs.

Abstract Background and purpose: Asthma is one of the most common chronic diseases in which inflammation plays an essential role in its pathophysiology. One of the secondary effects of asthma is depression, which is probably due to overlapping pathogenic mechanisms. One of the important mechanisms in the treatment of depression and asthma is to pay attention to removing inflammation and reducing oxidative stress. Purslane exerts its anti-inflammatory and antioxidant effects through NFqB and NOS pathways. This study aims to investigate the effect of the aqueous-alcoholic extract of the purslane plant on depression caused by experimental asthma using an Open Field Test and Forced Swimming Test in small laboratory mice.
Materials and methods: To investigate the aqueous-alcoholic extract of the purslane plant on depression caused by experimental asthma, 40 Syrian NMRI male mice were divided into 4 groups: control, asthmatic, and asthmatic receiving the extract at a dose of 50 mg/kg and 100 mg/kg. Syrian mice were injected and inhaled ovalbumin to develop asthma, and the control group received PBS solution in the same way. The treated groups received the extract at the same time as asthma induction.
Results: The results show that depression symptoms increased significantly after asthma induction. These symptoms were significantly reduced after the administration of purslane extract in a dose-dependent manner. The results indicated a significant increase in depression in the asthmatic group samples compared to the control group and also a significant decrease in depression in the groups treated with purslane extract compared to the asthmatic group.

Abstract Today evaluation of polymorphisms of the antioxidant enzyme-encoding genes, which affect the activity of antioxidant enzymes, could be used as risk prediction models for male infertility. This study aims to evaluate coloration of serum paraoxonase (PON1) activity levels in the semen and its L55M gene variants with risk male infertility. In a case-control study, semen samples were collected from 80 healthy controls and 128 infertile men at Fatemeh Al-Zahra IVF and Pastor Laboratory (Babol, Mazandaran, Iran). PON1 activity of semen samples was measured by spectrophotometric methods. Genotyping of all individuals based on PON1-L55M loci performed by PCR-RFLP and PCR-sequencing and molecular effects of leucine (L) to methionine (M) substitution were investigated by bioinformatics tools. Results showed a significant difference in genotype frequencies of PON1-L55M polymorphism between patient and control groups, and c.163T>A transition effect on the structure and function of PON1 protein. Also, TA genotype (OR=1.754, 95%CI=0.971 to 3.166, P= 0.062) and AA genotype (OR=5.067, 95%CI=1.366 to 18.789, P= 0.015) were associated with male infertility. Men with mutant allele (AA+TA) are exposed to be at the risk of male infertility (OR= 1.990, 95%CI= 1.118 to 3.54, P= 0.019). Also, the allelic analysis showed that the A allele was associated with the increased risk of idiopathic male infertility (OR= 1.749, 95%CI= 1.143 to 2.676, P= 0.010). Additionally, PON1 activity was higher in the TT (LL) individuals compared to the TA (LM) and AA (MM) men in both groups (LL> LM> MM). Since, the PON1-L55M gene variants are related to PON1 activity levels in the semen and serum paraoxonase is known as an important antioxidant calcium-dependent enzyme, it could be implicated in male infertility. Based on these findings, the presence of mutant allele (A) and or decreasing semen’s PON1 level may be an indicator/ prediction factor for male infertility.

Abstract Aim: Oxidative stress is one of the main factors has been implicated in pathophysiology of cataracts. Superoxide dismutase (SOD) can prepare the first line of defense versus detrimental reactive oxygen species (ROS) and Sirtuin (SIRT) confers protection against oxidative stress and retinal degeneration. Correlation of SOD1-50bp ins/del and SIRT1-rs7895833 polymorphisms with risk of cataracts is not studied currently. Therefore, we aimed to explore possible relationship between SOD1 (50bp ins/del) and SIRT1 (rs7895833) polymorphisms with the risk of cataracts in Iranian population. 
Methods: Our study design consisted of 200 patients with age-related cataracts and 200 healthy individuals as a control group. After DNA extraction, the identification of polymorphisms was conducted using PCR-based methods and data analysis was done by SPSS software. 
Results: A significant difference in SOD1 DD genotype distribution was observed between studied groups (OR: 3.42, P:0.037), the D allele was more frequent in patients in comparison with controls (OR: 1.68, P:0.009). Also, in the dominant genetic model for the D allele (comparison between ID+DD vs. II), ID+DD genotypes increased the risk of cataracts (OR: 1.62, P: 034). The association between SIRT1-rs7895833 polymorphism and cataract was significant in the AG genotype (OR: 2.37, P<0.001) and G allele (OR: 1.97, P<0.001). The SIRT1-1 polymorphism increased the risk of cataracts in the dominant tested inheritance model (OR: 2.34, P<0.001). In the combined analysis of two polymorphisms, there is an additive effect of the high-risk putative alleles about the risk of cataracts. Risk estimation according to the number of high-risk alleles showed that χ2 for linear trend for 0, 1, 2, 3 and 4 putative high-risk alleles is equal to 20.10 (P<0.001). 
Conclusion: The results showed that for the first time, SIRT1 rs7895833 and SOD1-50bp ins/del gene variations had additive effects on the risk of cataracts.

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 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 reproductive system is affected negatively by the organophosphate insecticide diazinon (DZN). Numerous adverse effects on the reproductive system are brought on by it, including testicles degeneration, sex hormone disruption, decreased spermatogenesis, poor sperm quality, and fertility issues. The goal of the current study was to look at how diazinon affected the sperm parameter, sperm viability, and levels of sex hormones in adult male rats. The mature male rat was divided into five groups for this experiment: control (did not receive any substance), Placebo group (only 0.9 percent saline solution was consumed), and the other three groups received DZN (diazinon was administered at doses of 5, 10, and 20 mg / kg for 30 days). Within 30 days after the most recent doses, animals were killed. Radioimmunoassay was used to evaluate the amounts of serum testosterone, LH, and FSH. Sperm parameters such as motility and count were measured by CASA system. Sperm viability was also calculated by eosin-nigrosin staining. Following the injection of DZN, a substantial decrease in testicular weight and sperm concentration was seen. Additionally, DZN caused a significant decrease in serum testosterone concentration as well as sperm viability. Comparing DZN groups to the control and sham groups, LH and FSH levels were higher in the DZN groups. DZN is harmful to the reproductive organs and spermatogenic cells of mammals. Application of DZN should indeed be restricted to a specific framework.

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.