Personalized Medicine Journal
Volume:8 Issue: 31, Autumn 2023

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.

Immunotoxins have been used for cancer treatment. The immunotoxin binds to the surface antigen on the cancer cell, enters inside the cell by endocytosis1, and destroys the cancer cell. In addition, the components of this type of drug and assembly based on peptide bonds2, and the creation of recombinant protein construction were among the requirements investigated in this study. In this bioinformatics research, membrane antigen structural, and functional properties on the surface of breast cancer cells were investigated and evaluated to target cancer cells. An EGFR3 antigen with a shorter amino acid length for positive binding and INS4, which has 110 amino acids, binding +, and a binding score of 0.99, was selected as the most efficient ligand using the AAASGG 3 (GGGGS) linker5, resulting in a six-recombinant structure. Hence, the targeted treatment of cancer through immunotoxin with the confirmation of the patent sequence led to the creation of a recombinant structure, which was analyzed with bioinformatics software. To ensure accurate results in the laboratory, we utilized Escherichia coli strain DH5 as a host during the cloning phase for plasmid DNA replication. This enabled a more precise and reliable replication process, thereby confirming the validity of our computational modeling, and the results of this research led to the modeling and simulation of the engineering structure of Cetuximab ZZpe38 immunotoxin. For future research, gene expression in mammalian cells will be the focus.

Precision medicine is a medical approach that involves customizing therapy for an individual by using extensive biological and external data. The rapid progress in the disciplines of molecular biology, gene sequencing, machine learning, and related technologies has facilitated the use of precision medicine. This approach utilizes the wealth of comprehensive information obtained from these advancements to improve the decision-making process in clinical treatment for individuals, particularly in real-time scenarios during the progression of a disease. Diabetes mellitus is a significant worldwide health issue, requiring the implementation of novel strategies to enhance patient outcomes. The efficacy of conventional treatment options that use a uniform approach has been shown to be limited in effectively addressing the heterogeneous character of the illness. In recent times, personalized medicine has surfaced as a revolutionary resolution, customizing treatment strategies in accordance with an individual's health attributes, lifestyle choices, and genetic composition. This review underscores the significance of genetic screening in forecasting susceptibility to diabetes and treatment response, while also emphasizing the potential of pharmacogenomics to optimize medication selection.

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.

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.

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. In this descriptive designed study, quality-controlled cDNA samples sequenced (RNA-seq) and mapped against a standard human genome version. Based on the results of this study, proinflammatory and inflammatory gene expressions were significantly upregulated. Upregulations of proinflammatory and inflammatory gene expressions early infection time might be indication for an early  innate immunity response.