Personalized and Precision Medicine Journal

Abstract In general, people with Autism Spectrum Disorders (ASD) have problems in social, emotional, and communication skills. Genome-Wide Association Studies (GWAS) have suggested a potential association of the C677T polymorphism of Methylenetetrahydrofolate Reductase (MTHFR) with autism spectrum disorders. The present study intended to investigate the relationship between this polymorphism of MTHFR and the severity of autism symptoms in two groups of children affected by autism and healthy children to elucidate its potential role as a risk factor for ASD.
study included 40 patients with autism and 40 healthy participants with matched age as control. The samples from the participants underwent ARMS-PCR for MTHFR genotyping.  
The CC genotype was reported in 50% (n=20) and 72.50% (n=29) of the children in the study and control groups, respectively, while the CT genotype was observed in 35% (n=14) of the study group and 17.50% (n=7) of the control group. Also, 15% (n=6) of the study group and 10% (n=4) of the control group had the TT genotype.
According to our results, the genotype distribution and allele prevalence were significantly different between the groups.

Abstract Exposure to low-frequency electromagnetic fields (LF-EMF) has been considered a global concern because of its harmful effects on human health (cancer, neurodegenerative disorders, etc.). According to the International Agency for Research on Cancer, EMF has been classified as a possible cancerous element for human health. Antioxidants such as vitamin C improve the damage caused by EMF by reducing oxidative stress. To evaluate the effects of EMF on the serum total protein, blood sugar, albumin and triglyceride, and the inhibitory role of vitamin C, 40 male BALB/c mice were recruited. Participants were randomly distributed into four groups 1- exposure to LF-EMF, 2- exposure to LF-EMF which received vitamin C (50 mg/kg), 3- exposure to LF-EMF which received vitamin C (100 mg/kg), and 4- control group (no exposure). The experimental groups (1-3) received LF-EMF (50 Hz, 4 mT, 4 hours/day, and 1 month) while both groups 2 and 3 had intraperitoneally injected vitamin C (50 mg/kg, 100 mg/kg) every other day basis respectively. The obtained results demonstrated higher triglyceride and total protein levels and lower albumin and blood sugar levels in the LF-EMF group compared to controls while vitamin C restricts their alterations (p<0.05). To sum it up, our data show that intraperitoneal injection of vitamin C restricts the effects of LF-EMF exposure on the biochemical parameters in mice. However, the antioxidant characteristics of vitamin C may be probably involved in the LF-EMF effects of biochemical parameters in mice.

Abstract Antibiotics are widely accessible. Nevertheless, food-borne bacteria exhibit a vast array of resistance. Utilizing natural ingredients like chitosan and chitosan-cefixime nanoparticles, which have potent antibacterial qualities, in conjunction with innovative technologies like chitosan loaded with antibiotics, the present research seeks to combat germs that are resistant to many drugs. Five strains of Escherichia coli O157:H7 were utilized to determine antibiotic resistance. The antibacterial properties of free cefixime and chitosan-cefixime nanoparticles were evaluated against strains of harmful bacteria. The findings demonstrated that E. coli O157:H7 comparatively had significant resistance to many antibiotics.
On the other hand, c chitosan-cefixime nanoparticles showed strong antibacterial activity against E. coli O157:H7, but free cefixime did not demonstrate any inhibitory zone. When compared to strains 1, 2, 3, 4, and 5 of E. coli O157:H7, the inhibition zones of chitosan-cefixime nanoparticles were 23.3 mm, 19.8 mm, 16.9 mm, 18.2 mm, and 22.4 mm, respectively. According to the results, chitosan-cefixime nanoparticles have better antibacterial action against dangerous pathogens than free cefixime. Therefore, using chitosan-cefixime nanoparticles for food preservation could be suggested.

Abstract Introduction: Recent scientific promotion reveals that medicine is currently at a transition stage from programmatic to personalized handling on in infectious diseases. Methods: Herrien, this research was performed to evaluation seropositivity for L. monocytogenes based on personalized medicine among the women with and without annals of miscarriage by indirect immunofluorescence test (IIFA). Moreover, the relationship of seropositivity with demographic factors was also investigated. Results: Our outcome showed that 26.92% (35 cases) of women with an involuntary miscarriage were seropositive for L. monocytogenes, while 11% (11 cases) of healthy pregnant women were found positive for L. monocytogenes (P = 0.001). The most case of listeria has been found in age group of 30-35 years old, but no notable difference was found among different groups (P = 0.245). Moreover, there was a considerable association between listeria occurrence and history of abortion when compared with healthy pregnant women (P = 0.001). In addition, early abortion and the number of pregnancy were significantly linked to Listeria- seropositive in patients with spontaneous abortion (P = 0.041; P = 0.034). Conclusions: Further researches are required to appraise the clinical importance of L. monocytogenesin in pregnant women with symptomatic and asymptomatic infection related to personalized medicine.

Abstract One of the most well-known side effects of anticancer drugs is the disruption of spermatogenesis. One of the most important causes of infertility in men is impaired spermatogenesis. Busulfan is a cytotoxic alkylating agent and belongs to the alkyl sulfonate group. This agent causes DNA damage by cross-linking with DNA. It kills spermatogonial stem cells. The use of healthy antioxidants can reduce the side effects of alkylating agents. In this study, we measured the protective effect of curcumin on testicular tissue of mice treated with busulfan by measuring BAX expression as an apoptotic inducer and Bcl2 as an apoptotic inhibitor. The expression levels of the two apoptotic regulatory genes Bax and Bcl-2 were evaluated by realtime PCR in four groups of mice (control, treatment with busulfan, treatment with curcumin, and treatment with busulfan + curcumin). It was observed in the busulfan group that bcl2 expression decreased, and Bax increased significantly, and the busulfan + curcumin group showed the opposite effect. Curcumin can be beneficial as a dietary supplement in cancer patients treated with drugs such as busulfan.

Abstract The increasing literature exploring the role of circulating miR-210 has clarified its potential as a promising biomarker for early detection, diagnosis and prognosis. Measuring circulating miR-210 levels could be a non-invasive method for early cancer detection. Even if, to date, most studies appear to be preliminary it seems that miR-210 will be a good target for drug development. In this study, we had detected the difference of serum miR-210 expression between health and breast cancer patients. total of 15 breast cancer patients were selected for the breast cancer (BC) group and 15 healthy people. The results showed The expression level of miR-210 in the serum of breast cancer patients was significantly higher compared with that in healthy individuals. Patients with breast cancer present increased levels of circulating miR-210; thus, circulating miR-210 may be a potential biomarker of tumor presence and therapeutic response in breast cancer

Abstract Despite the increasing number of diabetic patients, self-care plays an important role in the prevention and detection of various complications such as neurological disorders. The aim of this experiment was to investigate the main factors affecting diabetes type 1 and self-care. For this purpose, six volunteer subjects with diabetes type 1 were included. Their glucose levels together with the carbohydrate intake and other factors were recorded four times a day for 30 days. In order to perform statistical analysis, the one-way variance analysis, Pearson correlation coefficient, time series analysis, and the combined time series (panel) analysis were applied. The findings of this study demonstrated that the alteration in blood glucose levels was strongly influenced by carbohydrate intake, physical activity, stress level, amount of sleep, and insulin; while slightly influenced by pills and supplements use, hypoglycemia, insulin sensitivity, alcohol and cigarette use, and comorbidity. In four patients, the self-care score was normal, one patient exhibited high level and the reaming showed low level. For each patient, the error rate was as follows: 6.451, 6.095, 8.819, 7.368, 6.05, 5.856. Regarding to the loss of HbA1c rate after our study, people are advised to control their blood glucose levels based on individual preferences, conditions, lifestyle, and physiology for preventing severe diabetes type 1 conditions and extra cost.

Abstract The majority of ncRNAs are known as long non-coding RNAs (lncRNAs) whose length exceeds 200 nucleotides. H19, a lncRNA, is the transcription product of the H19 gene, an oncogene in breast cancer, and is highly expressed in cancer tissues compared with normal tissues. The expression level of H19 is associated with the oncogenesis, proliferation, invasion, metastasis, and drug resistance of breast cancer. H19 expression levels were detected in breast cancer plasma using qRT-Real-Time PCR assay in 50 breast cancer samples and 50 healthy control samples. The results showed that the expression of this gene in both the tissue and the plasma of patients increased compared to that of healthy individuals.

Abstract TERT It has been shown that TERT is overexpressed in 90% of human cancers, and genetic alterations in the proximal promoter of TERT are significantly associated with a variety of different cancer types. In recent years, a new mechanism of TERT regulation through the non-coding driver mutations (C228T and C250T) in the TERT promoter has been reported in several cancer types. In the present study, we investigated the relationship between the Single Nucleotide Polymorphism (SNP) rs2853669 and cervical cancer.
The study included 80 individuals, including 50 patients with cervical cancer and 30 healthy controls. The samples from the participants underwent sequencing and genotyping using the Polymerase Chain Reaction - Restriction Fragment Length Polymorphism (PCR-RFLP) method.
It was found that 16%, 24%, and 60% of the cervical cancer samples had the genotypes of AA, AG, and GG, respectively. In the control group, the frequencies were 13.33%, 50%, and 36.66% of the samples for the genotypes of AA, AG, and GG, respectively. 
According to our findings, there was a significant association between the recessive model GG vs. AA+AG and cervical cancer susceptibility.
 

Abstract Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune. Early diagnosis of RA remains challenging. A significant portion of RA patients also experience unremitting symptoms despite treatment. miRNA are involved in the regulation of autoimmunity- and inflammation-related processes. In this study, we evaluated the expression of miR-22-3p in serum of RA patients as a novel biomarker. Expression level of this gene in the blood serum of 30 people with RA compared with 30 healthy individuals by the qRT-PCR method. Results showed levels of miR22-3p were significantly higher in the serum of patients with RA in comparison with healthy control (p<0.0001). We suggest that miR 22-3p can be used as a biomarker in early detection and screening.

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 Present research on herbal food-derived phenolic compounds as angiotensin-I-converting enzyme (ACE) inhibitors has been well-documented. Punica granatum L. (pomegranate) is considered as a wonder fruit because of its substantial pharmacological properties. In fact, in- silico studies such as molecular docking can reduce the cost of studies and avoid unnecessary experimental investigations compared to other similar models of this kind of study.
This research is conducted in-silico screening of pomegranate peel to identify potential angiotensin converting enzyme (ACE) inhibitors. Molecular docking was employed as the computational system to evaluate the interactions of six selected compounds considering antihypertensive and potential ACE inhibitory effects. Compounds were evaluated using HyperChem through molecular mechanics (MM) and parametric method 3 (PM3).
This study demonstrates the limitations of in-silico models compared to in vivo studies. The potential of P. pomegranate peel compounds as a specific inhibitor and their transformation into a modern lead compound for therapeutic design showed a strong correlation between computational models and previous clinical findings. Luteolin, in particular, exhibited significant activity and is considered a potential lead compound in drug development. Further studies should explore the similarities between the structures of leuteolin and lisinopril, as luteolin could potentially be a new lead compound and a natural ACE inhibitor.

Abstract Colorectal cancer is the third most common cancer and the second leading cause of cancer deaths in the world. Risk factors such as obesity, low-fiber diet, sedentary, and alcohol have been implicated in the development of this cancer. Cells have many mechanisms in place to fight malignancy and cancer, one of which is the detoxification system that protect the cell against DNA damage. One of the essential components of this system is the glutathione s-transferase. In this study, the genotype of region -69 promoter of this gene in 150 colorectal cancer patients and 150 healthy people was investigated by the RFLP method. T/T genotype is significantly associated with colorectal cancer (P = 0.0001), C/T genotype did not show a significant association with colorectal cancer and its frequency was not significantly different in both healthy and patient groups (P = 0.074), Most genotypes in the two groups were homozygous C / C and did not show a significant association with colorectal cancer.

Abstract Cervical cancer is the most widely screened cancer in the world both in high- and middle-income countries. HPV has been implicated in 99.7% of cervical squamous cell cancer cases worldwide. Viral E6 and E7 genes expression leads to alterations of the cellular genome integrity, including structural and numerical chromosomal instability resulting in chromosomal mis-segregation and aneuploidy. Centromere protein M (CENPM) is an essential centromere component for chromosome separation. In this study, we evaluated the expression of this gene at mRNA level by qRT-PCR method on 20 cancer samples who previously had feather papillomavirus infection, The results show a significant increase in the expression of this gene in cancer samples.

Abstract Introduction: Nigella sativa (NS) is a widely used medicinal plant and appears to have a general health protective effect. As has been reported previously, pharmacological actions of NS have been explored including antidiabetic, anticancer, immunomodilative, analgesic, anti-inflammatory, spasmolytic, bronchodilator, hepatoprotective, renal protective, antioxidant properties, gastroprotective, antihistaminic, antibacterial, neuroprotective and antioxidative effects and etc. Methods: The present review aimed to give a personalized care for patients using detailed survey of the literature on and neuroprotective activities of the plant. Pubmed, Science Direct, Google scholar and Springer databases were searched from 1983 till January 2015. Key words were included: N. sativa, black seed, neuropathy, neuroprotective, brain and spinal injury, thymoquinone and posttrauma. Searching was limited to articles with English language. Review articles, case reports, abstract in symposium and congress, studies on N. sativa mixed with other plants were excluded. This study thus launches a huge resource for understanding the role of NS in in brain and spinal cord tissue damage after trauma with broad relevance for personalized medicine. Results: Results indicated that based on personalized medicine many of the herbal attributes of the herbal are due to the thymoquinone presence as its bioactive component, and therapy with NS notably decreased post-traumatic degenerative neurons and distorted nerve cells were not primarily treated in NS rats. In conclusion, NS can improve neuropathic status and neurological dysfunctions in the brain and spinal injury models. However, more clinical trials are necessary to clarify beneficial effects of NS its effective type and dosage for neuropathies management and its complications. Conclusions: Finally, NS treatment might be effective in detrimental the cerebral and spinal cord after trauma as personalized care for patients, and therefore shows potential for clinical implications.

Abstract Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. Non-alcoholic fatty liver disease is a spectrum of simple steatosis that is benign to non-alcoholic steatohepatitis (NASH) associated with fibrosis and inflammation. Genetic factors play an important role in this disease. The PNPLA3 gene (C > G) rs738409 polymorphism has been defined to be associated with increased liver fat content and liver damage in metabolic disorders. In this study, the association of this polymorphism with non-alcoholic fatty liver disease was investigated in the Mazandaran province population. Our study population consisted of 85 patients and 85 controls. Blood samples were collected from patients and DNA were then extracted by boiling method. Genotypes of this polymorphism were determined by PCR-RFLP method. There was a significant relationship between CG genotype and risk of NAFLD (P = 0.012).

Abstract Currently, little is known about the mechanism(s) of AgNP-induced toxicity. Many previous studies, however, have provided strong evidence for a link between the AgNP-mediated production of ROS and the subsequent generation of oxidative stress. In the current study, the effects of Ag nanoparticles on the MCF-7 breast cell line were examined, and the biomarkers related to stress oxidative including GSH, superoxide dismutase, catalase, and ROS generation were evaluated. The results showed that Ag nanoparticles induced intracellular ROS generation in a dose- and time-dependent manner. Therefore, various studies should be performed to investigate the toxic effects of this substance on different cells.

Abstract The causalGiven the known relationship between the HPV infection and some malignancies, it is critical to develop methods for quick detection and quantitation of certain HPV types while encountering a suspected lesion. Early HPV detection is greatly important in monitoring and treating the disease development and progression.  Detection of the viral DNA using PCR is the standard, noninvasive method for detecting cervical HPV infection. In the present study, we intended to develop a TaqMan genotyping assay that targets two types of high-risk HPV types (HPV 16 & 18) and two of the low-risk types (6 & 11).
The study included 75 samples positive for HPV, of which 37 were positive for HPV types 16 and 18, while 38 were positive for HPV types 6 and 11. The samples had been confirmed by a reference kit before. The samples underwent real-time PCR. Each reaction consisted of the 1X CAPITAL™ qPCR Probe Master Mix, specific primer pairs for HPV, and fluorescent-tagged probes.
According to our findings, all the samples genotyped using this method were compatible with the results by the reference kit, which was remarkable.
In conclusion, our type-specific approach based on real-time PCR could detect the entire samples positive for four types of HPV.

Abstract Background: A lot of patients are suffering from asthma. For decreasing the asthma symptoms, we studied the effects of conditioned medium (CM) of human amniotic membrane mesenchymal stem cells (hAM-MSCs) as a source of anti-inflammatory cytokines on splenocyte and lung tissue of asthmatic Balb/c mice.
Methods: Forty mice were categorized into four groups; ovalbumin (OVA)-induced asthma, CM-treated asthma, DMEM (Dulbecco's Modified Eagle Medium)-treated asthma, and saline control. Each group received related treatment. The lung alpha-smooth muscle actin (α-SMA)  and splenocyte inflammatory cytokines and IgE were examined through Western blot analysis.
Results: Western blot showed α-SMA overexpression in the OVA and DMEM groups compared with the saline group. CM therapy could significantly reverse it compared with OVA and OVA+DMEM categories by elevating IL-10 and IFN-γ and reducing IL-4, IgE, and TGF-β .
Conclusion: CM treatment could improve asthma symptoms by adjusting α-SMA in lung tissue and pro-inflammatory cytokines and IgE in splenocytes.

Abstract Human Papillomavirus (HPV) is a highly prevalent virus responsible for several types of cancers, including cervical, throat, and anogenital cancers. Early detection and diagnosis are crucial for preventing the progression of HPV-related diseases. In this study, we introduce a new approach based on Förster Resonance Energy Transfer (FRET) method to identify viral DNA, was designed for the conserved region of the L1 gene sequence in high-risk genotypes 16, 18, 31 and 33. In order to create suitable temperature conditions for the attachment and also to identify the fluorescent signal, real time PCR device was used. The results of the specificity test showed 100% specificity and the limit of detection level of the method was reported to be 1000 copies/µl of the virus in the sample. The results of clinical sensitivity in the range of 86-96% between deferent genotype and the rate of false negative results was in the range of 14-22%. Based on this, it can be said that maybe the developed method cannot be proposed as a suitable alternative, but due to the response time and lower cost, it can be proposed as a quick screening method.

Abstract Salmonella, a prominent foodborne pathogen, poses significant health risks, causing both intestinal and extra-intestinal infections. Recognizing the potential of lactobacilli as probiotics due to their ability to produce substances inhibiting multidrug-resistant bacteria, this study aimed to assess antibiotic resistance, pathogenic gene frequency, antibacterial effects of lactobacillus supernatant from kefir, and its impact on resistance and pathogenicity gene expression.
In Tehran hospitals, 150 isolates from 240 clinical samples were collected and identified as Salmonella Typhimurium using biochemical and serotype tests. Antibiotic sensitivity was assessed, and the frequencies of antibiotic resistance genes (tetA, tetB, and floR) and pathogenicity genes (sip, spvC, and invA) were investigated. Lactobacilli from kefir were isolated, and the minimum inhibitory concentration of lactobacillus supernatant was determined. The relationship between supernatant treatment and tetA and sip gene expression was examined using Real-time PCR.
Results revealed 38% of strains as Salmonella Typhimurium serotype, displaying high resistance to ampicillin, tetracycline, and nitrofurantoin. Pathogenicity genes invA and sip exhibited high frequencies of 100% and 70.2%, respectively. Lactobacillus supernatant showed an MIC of 80 μg/ml, effectively reducing tetA and sip gene expression by 42.2% and 55.7%, respectively.
In conclusion, the study underscores the high antibiotic resistance in Salmonella Typhimurium and suggests Meropenem, Trimethoprim Sulfamethoxazole, and Ampicillin-Sulbactam as effective treatments. Moreover, lactobacillus supernatant demonstrated significant potential against Salmonella Typhimurium, highlighting lactobacilli as promising probiotics. This health-oriented strategy presents a viable solution for treating Salmonella infections and preventing their spread.

Abstract The second most common cancer and the fourth leading cause of death in women is cervical cancer. In 90% of cases of human papillomavirus infections, HPV is the cause of this cancer. More than 200 different types of the virus have been identified, including low-risk and high-risk variants. According to statistics, infections from types 16 and 18 of the virus account for 70% of cervical cancers. This cancer is preventable, and one of the ways to prevent it is to have regular screenings. Probe-based real-time PCR methods are more accurate and sensitive methods for detection. In this study, we performed HPV typing with probed base real-time PCR in 50 genital wart samples and checking the relationship between questionnaire information.

Abstract Nanotechnology involves the creation and manipulation of materials at nanoscale to create products that exhibit novel properties. Nano-TiO2, as one of the top five nanoparticles in annual production, is widely applied in industries ranging from healthcare to drug delivery. The properties of nanoTiO2 have raised concerns regarding toxicity. Annexin V-FITC/PI double staining and a flow cytometer were used to detect apoptosis. A significant increase in apoptosis was observed at concentrations of TiO2-NP of 50-100 µg/ml, varying between 25-40% apoptosis by 24 h. To further investigate the aptotic and toxic effects of these substances, it is recommended that this study be performed in the in vivo phase.

Abstract Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder. The etiology of MS is not clear but genetic and epigenetic factors are involved in MS development. Studies have shown that IL7R gene polymorphisms is capable of changing MS susceptibility. We investigated the association of MS with rs11567658, rs11567686 promoter polymorphisms of IL7R gene in western provinces of Iran. In the present study, 187 MS patients and 190 healthy control were evaluated. Polymorphic regions of IL7R promoter were amplified by appropriated primers and polymorphisms were then evaluated by RFLP method followed by validation via Sanger sequencing. Results shown rs11567685 and rs11567686 are significantly associationed with MS (P = 0.017 P = 0.046), significant association of these polymorphism with age was also found (P = 0.002). This study showed that IL7 receptor gene polymorphism has a key role in MS development and may be important opportunity for development of therapeutic and diagnostic strategies in context of personalized medicine.

Abstract PAI-1 has become recognized as a central molecule linking pathogenesis and progression of thrombotic vascular events, including stroke. Clinical and experimental studies show that PAI-1 deficiencies cause accelerated fibrinolysis and bleeding, whereas elevated PAI-1 plasma levels are associated with vascular thrombosis. Raised PAI1 plasma levels are related to a 1-bp guanine deletion/insertion (4G/5G) polymorphism in the promoter of the PAI1 gene. The 4G allele is associated with higher plasma PAI1 transcription and activity. In the current study, the association of higher PAI-1 plasma levels and the prevalence of the 4G/5G polymorphism in the PAI-1 gene promoter region in young patients with stroke were explored. Significantly, higher PAI-1 levels were observed in patients when compared to controls (p =002). The 4G/5G polymorphisms were significantly associated with increased PAI-1 levels, with the variant homozygous 4G/4G corresponding to mean values in patients versus controls.