Personalized and Precision Medicine Journal

Abstract Introduction: MicroRNA-124 (miR-124) is moderated in some human malignancies and is associated with tumor advancement. But, its expression and clinical importance in ovarian carcinoma is still unclear. Thus, the goal of this study was to feature the clinical importance of personalized miR-124 expression in ovarian carcinoma. Methods: 94 women ovarian cancer tissues and 26 normal ovarian tissues were accumulated from patients. We used Real-time PCR to quantify the expression of personalized miR-124 in clinical ovarian carcinoma specimen and normal tissues. Moreover, we measured the miR-124 relationship with clinicopathologic characteristics and the ovarian carcinoma survival. Results: The lesser expression of miR-124 in tumor tissues can be found in compared with normal tissue using PCR method (P < 0.05). Our data exhibited that there is a notable association among low expression of miR-12 and clinical staging of ovarian carcinoma (P = 0.023). Nevertheless, miR-124 expression was not notably associated with age (P = 0. 671), differentiation status (P = 0.512), lymph node metastasis (P = 0.415) and histological subtypes (0.547). Kaplan-Meier survival analysis and log-rank test were applied in present study. These tests showed the less expression on patients had markedly short-term survival time in comparison with high expression group (P = 0.022). Multivariate Cox proportional hazards model analysis revealed that less expression of miR-124 and clinical staging were contribute to short-term survival in patients with ovarian carcinoma. The HR of the low miR-124 expression group was calculated to be 2.532 (95% CI: 1.572-9.237, P = 0.021), (clinical staging HR: 2.532; 95% CI: 1.321-9.241, P = 0.032).
Conclusions: These findings suggested that personalized miR-124 could be considered as an independent prognostic factor for ovarian carcinoma patients. Our findings suggested that low expression of personalized miR-124 has prognostic worthiness in ovarian.

Abstract Epithelial to mesenchymal transition (EMT) is a process by which epithelial cells lose their epithelial characteristics such as cell polarity and cell–cell contact, and gain mesenchymal properties, such as increased motility. In colorectal cancer (CRC), EMT is associated with an invasive or metastatic phenotype. EMT induced by special transcription factors such as EMT-TF. The ZEB and Twist proteins were defined as EMT‐TFs. All of these factors are expressed in embryogenesis and are capable of regulating developmental programs. In the current study, we evaluated Zeb1 and Twist1 expression levels in 30 CRC patients and 30 adjacent tissue from same patient. Our findings revealed a significant association of Zeb1 and Twist1 expression levels with CRC incidence, suggesting their potential for targeted therapy of disease.

Abstract Lung cancer is the deadliest cancer in Iran after gastric cancer. The vast majority (85%) of cases of lung cancer are due to long-term tobacco smoking. About 10–15% of cases occur in people who have never smoked. These cases are often caused by a combination of genetic and environmental factors. Many human cancers are the result of mutations in the RAS family, and lung cancer is no exception. In this study, mutations in codon 12 and 13 of exon two were performed in 50 lung tumors from the Iranian Institute of Oncology. The exon 2 of the gene was amplified by PCR and sequenced for detection of the point mutation in codon 12 and 13. Of the 50 samples, 13 had mutations in codon 12 and 13, of which only two patients had single mutations in codon 12. No significant relationship was not found between age (P = 0.43) and gender (P = 0.37) and mutations in this gene. No significant relationship was found between disease stage and mutation in this gene (P = 0.51). Identifying k-ras gene mutations as an oncogene and having an effect on the treatment process can help the physician to choose the appropriate treatment.

Abstract Lung cancer is the leading cause of cancer deaths worldwide. Approximately 25% of nonsmall-cell lung cancers have mutations in the EGFR gene, most of which occur in hotspot regions in exons 18, 19, 20, and 21. In-frame deletions in exon 19 (~50%) and the L858R point mutation in exon 21 (~40%) are associated with a favorable response to EGFR tyrosine kinase inhibitors. In this study, mutations of two exons of 19 and 21 in 50 lung cancer tumor samples were investigated by the sequence method. From 50 lung cancer patients, 8 (16%) patients had an L858R (c.2573T>G) mutation, 6 (12%) patients had deletion type 1a mutation, and one patient had deletion type 1b mutation. Examining the sequence of candidate genes associated with lung cancer can be very important in choosing the right treatment approach.

Abstract  
Cervical cancer is a common and deadly cancer among women around the world. One of the genes associated with many cancers is the CYP1B1gene.Some studies have shown that polymorphisms in the CYP1B1 gene can induce hyper activation of proteins and increase the incidence of several cancers. In the present study, we examined the association between the CYP1B1 C4326G polymorphism and the risk of cervical cancer.60 newly diagnosed patients with cervical cancer and 60 cancers-free controls.DNA was extracted by Salting-out method, Restriction fragment length polymorphism PCR was employed to determine the genotype of the CYP1B1 C4326G polymorphisms. the frequencies of the three genotypes (CC, CG, and GG) of CYP1B1 C4326G in cervical cancer cases and controls were 68.0, 25.4, 6.6%and 73.1, 21.4, and 5.5 %, respectively, and there was a significant difference between the two groups (χ2=7.41, P=0.02).  
 


Cervical cancer,CYP1B1, RFLP-PCR, Human papilloma virus

Abstract PTEN is a tumor suppressor gene with important roles in apoptosis. This gene is located on chromosome 10q23 and is one of the most frequently inactivated genes in cancers. Severe underexpression of PTEN has been reported in several types of cancer, including endometrial, prostate, breast, and brain cancer. Also, this gene is epigenetically silenced through aberrant hypermethylation of CpG islands on its promoter. The present study investigated the promoter methylation and expression levels of PTEN in patients with Non-Small Cell Lung Carcinoma (NSCLC).
The study included 20 patients with NSCLC, whose bisulfite-treated DNA samples were investigated using the Methyl-Specific PCR (MSP) with primers specific for either methylated or non-methylated forms of PTEN. PTEN expression was also assessed using real-time PCR.
 20 samples from NSCLC patients, 70% (n=14) showed PTEN underexpression, while 85% (n=17) had PTEN promoter methylation. Also, 12 of 17 (70%) samples with PTEN promoter methylation had concomitant PTEN underexpression.
According to our results, there was a significant correlation between the PTEN promoter methylation and NSCLC. PTEN underexpression and promoter methylation were also significantly correlated.

Abstract Genetic studies, there is a potential association of RELN with some psychological
disorders such as Autism Spectrum Disorders (ASD) schizophrenia (SCZ). The RELN
gene is located on chromosome 7q22.1 and encodes a large secretory protein of the
extracellular matrix (Reelin). In the present case-control study, we intended to investigate
the relationship between the rs362746 polymorphism of RELN and schizophrenia in a
group of schizophrenic and healthy subjects from northeastern Iran.30 unrelated schizophrenic patients and 30 matched control subjects were recruited The samples
from the participants underwent PCR and sequencing for RELN genotype identification.he genotype distribution for  both study and control groups were not in Hardy–Weinberg equilibrium(P>0.05).However, it was found that the prevalence of
rs362746 polymorphism was significantly different between the groups. the present study supported the evidence that rs362746 polymorphism of RELN was a
genetic factor for schizophrenia susceptibility. However, there is a need for replication
studies on different populations and further investigations on the sex-specific association
of this gene with schizophrenia.

Abstract Cancer is largely a disease of older people; the median age for cancer diagnosis in industrialised countries is approaching 70 years of age and is expected to increase. The morbidity and mortality rates of various tumors increase with age, and thus, malignant tumors are generally defined as aging diseases. The immune system has an ambiguous role in cancer, as it plays an important immune surveillance role in the antitumor response but is also closely associated with the initiation and progression of tumors. With aging we assist to the erosion of the immune response called immunosenescence. This deregulation particularly affects the T cell compartment of the adaptive immune response. In addition to the accumulation of genetic mutations, many researchers believe that immunosenescence may also play an important role in
the tumoral process. In the future, targeting immune senescent cells may be a novel interventional opportunity in cancer patients.

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology that results in progressive joint destruction and ultimately to disability. Currently effective biologic therapies, exist for approximately  40% of patients, but disease activity remains inadequately controlled in others. Therefore, it is crucial  to identify specific markers that predict therapeutic response in various patients, prior to the initiation of therapy.  DNA methylation , as a epigenetic factor, is increasingly being explored as a potential theranostic biomarker. It has been suggested that DNA methylation might contribute to RA development, nonetheless , with conflicting results. Epigenetic modules have provided a possible interface through which genetic and environmental risk factors  contribute to the susceptibility and pathogenesis of RA. Hence,  epigenetic regulators may provide promising drug targets to develop novel therapeutic drugs for tailored treatment of RA patients. Here we review the current knowledge regarding the role of DNA methylation in RA and indicate its potential therapeutic implications.

Abstract The pathophysiology and molecular pathways of breast cancer (BC) are still unclear, but it appears that BC is caused by the interaction between genetic susceptibility and environmental factors. Epidemiology studies have shown the increase risk of BC through polycyclic aromatic hydrocarbons (PAH) exposure. Environmental carcinogens induce disease pathways by altering the expression of specific genes that may be a consequence of epigenetic modifications. In order to understand the effects of PAHs in the BC risk, the epigenetic pathway may consider as an important key and likely play a role in BC initiation. Novel epigenetic  biomarkers and treatments hold promise  in the approch of personalized medicine. Here, we focus to review the epigenetic factors in relation to polycyclic aromatic hydrocarbons exposure that may influence BC risk.

Abstract Background: Lots of people die from heart failure (HF) because of fibrosis formation. As injured myocytes deregulated MMP-2, MMP-4, TIMP-2, Ang, plasma renin activity  (PRA), and ACE leading to fibrosis, their regulation can improve HF. One of the most effective treatments for heart failure is the use of hAMSCs-CM, which has been shown to improve heart function and reduce symptoms. The study innovation was the investigation of the in vivo mode of action of hAMSCs-CM on HF fibrosis focusing on the mentioned proteins for the first time. We expected that this study partly fill the scientific gap in HF treatment.
Methods: Frothy rats were divided into 4 groups; Control, HF, culture medium, and CM. To induce HF, isoproterenol (ISO) was injected into all animals except for the control. CM were injected into the CM group and the culture medium group received culture medium. Then, cardiac functions were measured using echocardiography and serum fibrosis was evaluated by ELISA.
Results: HF model showed decreased MMP-2, MMP-4, Ang, PRA, and ACE and increased TIMP-2, whereas hAMSCs-CM therapy reversed them compared with controls.
Conclusion: Our result has partially filled the HF treatment’s gap as hAMSCs-CM improved cardiac function and reduced cardiac fibrosis and the serum fibrogenic proteins.

Abstract Myeloproliferative neoplasm (MPN) is a neoplasm with three categories; essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) and it usually is diagnosed through mutation analysis in several essential genes; JAK2, MPL, CALR. The mutations of mentioned genes in 50 patients with MPN and 50 healthy volunteers were determined via allele-specific PCR and sequencing. Based on the results, MPN and its subtypes have significant relation with mutations (p<0.05). JAK2 (exon 14) mutation was related to MPN and its subtypes except for ET and CALR (exon 9) type 1 was merely related to ET, but CALR (exon 9) type 2 mutation was more prevalent in MPN and PV (p<0.05). None of the mutations co-occurred simultaneously. There was no evidence of mutation in JAK2 (exon 12) and MPL (exon 9 and 10) in our study, so they are unsuitable diagnostic candidates. So, mutations in JAK2 (exon 14), and CALR (exon 9) type 1 and 2 are essential in MPN diagnosis in Iranians.

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 Multiple sclerosis (MS) is a long‐term disease that is frequently progressive and affects the central nervous system (CNS). This in turn breaks down the myelin sheath the protective covering around nerve fibers. Damage to myelin leads to a breakdown in nerve communication and can cause a number of neurological conditions. This study examines recent approaches towards increasing remyelination in the multiple sclerosis (MS) population as the protection of oligodendrocytes and promotion of remyelination are essential therapeutic goals. Materials and methods: A search was performed in national and international databases with the use of specific keywords. This search resulted in the identification of 235 articles, on “remyelination” and “multiple sclerosis”. Seventy articles were included in this review from 2000 up to 2020. These findings lead to the conclusion that already established immunomodulatory therapies have some benefits for reduction of myelin breakdown, but are rather poor at promoting remyelination, most notably in progressive MS.Controversially during the last years a change has been made towards compounds targeting (symptomatic) inflammation as well as remyelination. These interventions may optimize function and may promote axonal conduction. These strategies, including stem cell therapy, growth factors, small molecules and gene therapies hold promise in future treatment of MS. Not only are they trying to stop further loss of myelin, but also attempt to repair what damage has already been done.

Abstract Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by immune dysregulation and multi-organ involvement. Central to its pathogenesis is the CD154/CD40 signaling axis, which orchestrates key immunological processes, including T-B cell collaboration, dendritic cell activation, and cytokine production. Recent findings have expanded the scope of CD154 beyond its classical receptor CD40, identifying integrins as alternative receptors, thus broadening its biological impact. These discoveries underline the complexity of CD154's role in SLE and its potential as a therapeutic target. First-generation CD154/CD40-targeted therapies showed promise but were hindered by thromboembolic complications. However, second-generation therapeutics, including monoclonal antibodies, small molecules, and gene-editing technologies, exhibit improved safety and efficacy profiles. This review delves into the molecular and cellular mechanisms of CD154 in SLE, explores its emerging roles through integrin interactions, and evaluates the therapeutic advancements targeting this axis. The findings highlight CD154 as a central mediator in SLE pathogenesis and a compelling target for innovative treatment strategies.

Abstract This issue is related to the time when the magazine was published in Persian language. The magazine has been published in English since 2019. You can download all the articles.

Abstract Introduction: Regarding to ethnicity and racial complexity in socially heterogeneous and refugee-accepting countries, family approach for organ donation request from a deceased donor could be unpredictable. The problem could be settled by adherence to coordinator-donor conformity rule besides principals of donor family care. Methods: In our OPU, we have recruited a considerable quantity of organ donation coordinators (mainly medical students) with different ethnicities, dialects, and personality types. In this study, we have assessed family approach success indices in two different eras (Before 2017 and after this time). These included overall family consent and refusal rates, time interval from the first interview to actual donation, the weight of different age clusters in the donor pool and etc. Results: Considerable progress was achieved in all family approach success indices. Overall family consent rate was found to be increased from 61% in the first era to 88% in the second era (P = 0.005). The mandatory time for the coordinators to obtain family consent dropped significantly. (12.2 ± 8.6 to 6.3 ± 4.8 Hr, P = 0.02). Furthermore, the weight of precious young donors (< 40 years) increased from 36% to 47% (P = 0.05) due to more success rate in more difficult young cases. Conclusions: Appropriate recruitment of organ donation coordinators warranties more successful organ donation efforts after proper training. Decision making about suitable usage of every coordinator in a specific part of the family approach stages should be done case-by-case. This strategy could be of great benefit in ethnicity and cultural variant communities.

Abstract Numerous studies have been conducted to investigate the relationship between genetic factors and drug use tendency, many of which have shown a significant correlation between genetic factors and drug use, especially heroin and cocaine. The most important site of drug action is the brain, which contains a variety of nerve receptors. Dynorphins are opioid peptides derived from the prodynorphins precursor (PDYN). These opioid peptides are capable of binding to the three types of opioid receptors. Studies have shown that heroin and cocaine use is associated with increased PDYN gene expression in specific areas of the brain. In this study, we investigated the association between rs910080 polymorphism in the 3'UTR region and the number of VNTR sequences in the promoter region with the tendency of heroin use in 155heroin addicts and 150 control with RFLP method. Results showed a significant relationship between heroin abuse and CC genotype in rs910080 polymorphism (P = 0.001), but no significant relationship between VNTR promoter repeats and heroin abuse. Rs910080 polymorphism can be used as a distinguishing factor.

Abstract Chemokine CXCL9 is a member of the CXC family and has an important role in the chemotaxis of immune cells. In this study,  changes in the expression of gene CXCL9 in prostate cancer and adjacent healthy tissue was investigated. The prostate cancer tissues and the corresponding adjacent tissues used in this study were collected from 30 patients. qRT-PCR was performed for evaluated changes in the expression of gene CXCL9 in prostate cancer and adjacent healthy tissue. The mRNA levels of CXCL9 in prostate cancer samples was greater than normal samples (P=0.04), The results suggested that the mRNA expression levels of CXCL9 were positively associated with prostate cancer.

Abstract Bipolar Disorder (BD) is a cognitive and behavioral disease with mood fluctuation  . The 6th global problem is in adults. Disease susceptibility is affected through genetic factors, the epigenetic process marked the disease phenotype. On the other hand, the importance of DNA methylation in some neurobiological and cognitive activities such as brain development processes and activity includes psychiatric diseases like BD. Numerous long intergenic noncoding RNAs were found that regulate gene expression of several diseases and are involved in the brain and cognitive development as well as psychiatric disorders such as BD.
Despite advances in neuropsychological or biological markers discoveries which predict personalized treatment efficacy,   the clinical history and exhibition are careful and predictable markers for patient categorizing and treatment management. The aim of individualized medicine is to find vulnerability or preservative factors through genetic change.
Genetic, epigenetic factors, imaging, psychopathology and biomarkers can affect new treatments. Various studies such as family, twin, and adoption studies , linkage analysis indicated the association of HPA axis genes with vulnerability to BD. Personalized medicine applications in psychiatry focus on descriptive psychopathology and phenomenology via precise analysis and attention to each patient’s impaired brain and mood processes.
The precision medicine studies concentrate on response to lithium, main treatment of BD  , frequent mood diseases , antidepressant resistant prediction ,risk and outcome assessment. Precision medicine is a hopeful way to develop new treatments based on individual genetic features. Personalized medicine in psychiatric disorder is in the infancy phases, but promising approaches were developed for complex diseases treatment with human genome sequencing.

Abstract Warning of the World Health Organization (WHO) indicates that novel coronavirus (COVID-19) is pandemic and causes global concern. COVID-19 has acute respiratory symptoms which leads to die in many cases through the world. We have found seven variants in 300 patients based on Next Generation Sequencing (NGS) which are related to infectious disease. According to the databases, we confirmed that rs2660 and rs1800450 have association with COVID-19 in the Iranian population.

Abstract The most common human archival specimens are formalin-fixed and paraffin-embedded tissues. PCR-based techniques have been coupled with new developments in the extraction of DNA from FFPE. Herein, we report the results of a comparison of different methods of DNA extraction from FFPE specimens, including phenol-chloroform, salting-out, and silica-based commercial kits. Results showed no significant differences between the amounts of DNA obtained from each of the extraction methods studied; however, the salting-out DNA extraction method described is much easier and less toxic than the phenol–chloroform method.

Abstract Nowadays, there has been a considerable advance of personalized medicine on a
scientific basis and clinical demands in cardiovascular diseases. This study investigated
a history of coronary artery bypass graft surgery a strong determinant of inferiority of
organ in cadaveric liver donation. In this study, fate of 14 potential deceased liver
donors with a history of coronary artery bypass graft surgery has been investigated.
This report shows that careful gross and microscopic investigation of the liver is the
key to extract suitable life savior livers from donors with advanced age.

Abstract Lung cancer is the leading cause of cancer death in men and the second leading cause of cancer death in women worldwide. FGFR is involved in a variety of cellular processes including angiogenesis, wound healing, tissue repair, and tumorigenesis. Recently, a common polymorphism in the transmembrane domain of the FGFR4 gene, Gly388Arg, has been reported to correlate with alteration of cell migration in vitro and with disease progression and/or survival in breast, colon, prostate and lung cancer. To evaluate the prognostic significance of the FGFR4 Gly388Arg polymorphism in lung cancer, we analyzed a case-control study of 110 lung cancer patients and 90 healthy control. Genomic DNA from whole-blood specimens was extracted using Salting-out method. Quality of DNA was evaluated by electrophoresis. To determine the distribution of FGFR4 Arg388 and FGFR4 Gly388 alleles in lung carcinoma patients, RFLP-PCR was used. In this study demonstrated that there was no relationship between polymorphism of FGFR4 Gly388Arg gene and lung cancer. Also, no significant relationship was observed between this polymorphism and clinical and pathological features of patients. It is suggested that the large casecontrol studies are needed to detect genetic determinants affecting patients’ prognosis, with the promise of targeting these putative genetic determinants to provide new therapeutic tools for patients with lung cancer.

Abstract Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. Epithelial-mesenchymal transition (EMT) is defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. EMT is a vital process for large-scale cell movement during morphogenesis at the time of embryonic development. Tumor cells usurp this developmental program to execute the multi-step process of tumorigenesis and metastasis. Understanding the biological intricacies of the EMT may provide important insights that lead to the development of therapeutic targets in pre-invasive and invasive breast cancer, and could be used as biomarkers for identifying tumor subsets with greater chances of recurrence, metastasis, and therapeutic resistance leading to death. The purpose of this article is to investigate the association between EMT and breast cancer.