Where Innovations Meets Personalized and Precision Medicine
Volume & Issue: Volume 10, Issue 36, Original article, Winter 2025, Pages 1-53 
Number of Articles: 6

The Evolving Landscape of Drug Resistance: From Mechanisms to Therapeutic Strategies

Pages 1-11

https://doi.org/10.22034/pmj.2025.2054050.1055

Yousef Roosta, Neda Abedi

Abstract Drug resistance is a major obstacle in the effective treatment of cancer, severely impacting patient outcomes and complicating therapeutic strategies. The development of resistance is multifactorial, involving a combination of genetic and epigenetic changes within cancer cells, alterations in drug metabolism, increased DNA repair mechanisms, overexpression of drug efflux pumps, and complex interactions with the tumor microenvironment. These factors work synergistically to render traditional chemotherapy and targeted therapies less effective over time.
Recent advances in molecular biology, particularly next-generation sequencing and the CRISPR-Cas9 gene-editing tool, have significantly enhanced our understanding of the underlying mechanisms driving resistance. These technologies have enabled researchers to identify novel genetic mutations and signaling pathways that cancer cells exploit to evade treatment, offering new potential targets for therapeutic intervention. Additionally, the dynamic role of the tumor microenvironment, including immune cells, stromal cells, and extracellular matrix components, has emerged as a key factor influencing drug resistance, further complicating treatment strategies.
To address these challenges, several innovative therapeutic approaches are being explored. Combination therapies, which involve the use of multiple drugs targeting different pathways simultaneously, hold promise in overcoming resistance by attacking cancer cells from multiple fronts. Immunotherapy, which harnesses the body's immune system to target cancer cells, is also showing significant potential in resistant cancers. Furthermore, nanomedicine, which uses nanoparticles to deliver drugs directly to tumors, may improve drug efficacy and minimize resistance.
Despite these advancements, much remains to be done. Ongoing research focused on identifying reliable biomarkers, developing personalized medicine approaches, and understanding the intricate relationship between cancer cells and their microenvironment is essential. This review aims to provide a comprehensive overview of the current state of knowledge regarding drug resistance in cancer, emerging therapeutic strategies, and future research directions in this critical field.

Therapeutic Candidates for COVID-19: A Comprehensive Review of Antiviral, Immunomodulatory, and Emerging Treatments

Pages 12-18

https://doi.org/10.22034/pmj.2025.2048597.1049

Hossein Fazli

Abstract Background and Objectives:
The coronavirus first appeared in Wuhan, China, in late November 2019, and has since spread to more than one hundred countries. COVID-19 has been declared by the World Health Organization as a Public Health Emergency of International Interest. This has been the result of a virus now having reached pandemic proportions and there not being an effective vaccine or antiviral treatment. In this article, we aim to highlight each current drug being tested for potential effectiveness on this disease.
Methodology: The research is a descriptive review conducted by a search in reputable scientific databases, including Scopus, Google Scholar, and PubMed, utilizing the phrases virus, coronavirus, COVID-19, SARS-CoV-2, and treatment. The latest expertise:given that the development and efficacy of antiviral drugs require substantial time, monotherapy for other diseases may represent the most efficient therapeutic option for a certain condition. Pharmaceuticals with broad-spectrum efficacy, including Bevacizumab, Methylprednisolone, Fingolimod, fluoxetine, Ritonavir, chloroquine Fesnate, remdesivir, and Favipiravir, are currently under investigation as prospective candidates in various clinical trials.
Conclusion: To conclude, all these drugs are potentially useful in the prevention and treatment of diseases. But none of these drugs is a cure-all, specific treatment for COVID-19. Therefore, we must continue to search for an effective drug treatment for this disease until we have a proven successful agent available.

Association Between Semen Paraoxonase-1 Activity Level and L55M Gene Variants with Risk of Male Infertility

Pages 19-28

https://doi.org/10.22034/pmj.2025.2046951.1046

Hanie Mortezapour, Abasalt Hosseinzadeh Colagar, Fatemeh Fallah, Ali Taravati, Seyed Gholam Ali Jorsaraei

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.

Approaches to Traditional Vaccines and the Development of New Person-Centered Vaccines

Pages 29-35

https://doi.org/10.22034/pmj.2025.2044591.1043

Ramesh Ranjbar, Romina Hosseinzadeh

Abstract According to the World Health Organization, immunizations save between two and three million lives every year by avoiding illness. In addition to these immunizations, eradicating human smallpox was possible and is close to eradicating polio. In addition, vaccines have a significant economic impact because they prevent hospitalization of patients and other care costs. A vaccine is a biological product that specifically leads to acquired immunity against a pathogenic pathogen and prevents the disease in the face of the main pathogen in a person. Therefore, vaccines are an important tool for maintaining health in the global community. Traditional vaccines have been used against a wide range of pathogenic pathogens, both viral and bacterial, and have been successful. However, these vaccines do not work and are ineffective against pathogens that change rapidly in terms of genetic material and surface epitopes.
During the last decade, vaccines based on nucleic acids, viral vectors and biomaterials have shown promising results. This study has discussed an overview of traditional vaccines, mRNA-based vaccines, viral vector-based vaccines, and biomaterials.

Systematic Review: Application of Artificial Intelligence in Breast Cancer Therapy

Pages 36-47

https://doi.org/10.22034/pmj.2025.2048503.1047

Maryam Abbasi Saeidi

Abstract Background and Objective: Gene therapy can be employed to treat several disorders, including cancer. Globally, women are more frequently diagnosed with breast cancer than any other cancer type, underscoring the necessity for innovative strategies. Algorithms driven by artificial intelligence can enhance the gene therapy process for breast cancer by analyzing vast data sets, identifying intricate patterns, and classifying those patterns. This project aims to perform a literature evaluation focusing on the therapeutic uses of artificial intelligence in gene therapy for breast cancer.

Materials and Methods: For the aim of this study, data was gathered by reading previously published articles and searching the PubMed database for phrases that were relevant to the question being investigated.
Findings: The AI-driven algorithm analyzes complex molecular pathways in the human body, replicates the knowledge of scientists and physicians in clinical research, and simulates biological processes related to gene regulation, thereby improving the effectiveness of gene vectors, managing gene and drug delivery parameters, and modeling cellular behavior. This method diminishes medical errors and promotes early disease identification and drug efficacy forecasting, thereby providing patients with optimal results from advanced treatments like gene therapy with minimal side effects.
Conclusion: Over the period of the past decade, a multitude of efforts have been made to deploy various gene therapy procedures for breast cancer patients, to achieve the highest possible level of efficacy while minimizing the risk of adverse consequences. As a result, artificial intelligence is considered to be a powerful tool for improving early diagnosis and efficient gene therapy for breast cancer.

Prevalence and Potential Zoonotic Risk of Campylobacter spp. in Dairy Cattle from Golestan Province, Iran

Pages 48-53

https://doi.org/10.22034/pmj.2025.2053062.1054

Ali Bahoosh, Ezzat Allah Ghaemi, Abdollah Ardebili, Sayeh Ghaemi, Ailar Jamalli

Abstract Background: Campylobacter, a zoonotic pathogen, is the primary bacterial agent responsible for gastrointestinal (GI) infections in humans. Domestic animals, including cattle, are reservoirs of this bacterium, and can be one of the main sources of infection transmission to humans. This study aimed to investigate the prevalence of Campylobacter species using a multiplex PCR assay in cattle in the Gorgan province.
Materials and Methods: A total of 200 fecal samples were collected from healthy dairy cattle and genus and species were identified using multiplex PCR.
Results: The frequency of the genus Campylobacter in 200 samples in our study was 17.5% (35 cases), C. jejuni and C. coli species were not identified in these 35 cases.
Conclusion: Isolating Campylobacter from animal fecal samples is a challenging process, but this study showed that Campylobacter contamination was relatively high in cattle in the Gorgan province, and its transmission to humans through meat consumption must be monitored.