Personalized and Precision Medicine Journal

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 Introduction: In this context, the use of medicinal plants as a natural and effective remedy for relieving Menstrual pain has been acknowledged in the western border region of Iran, serving as an alternative or complementary therapeutic approach. The aim of this study is to identify the medicinal plants employed in this region of Iran for the treatment of menstrual pain.
Methodology: This review study employed keywords such as medicinal plants, Iran, menstrual pain, and the provinces of West Azerbaijan, East Azerbaijan, Ardabil, Kurdistan, Kermanshah, Ilam, Khuzestan, and their cities, along with ethnobotany terms. Databases such as Google Scholar, SID, MegaIran, PubMed, and Scopus were utilized for article searches. Ethnobotanical articles related to the topic were selected for text review.
Results: Based on the ethnobotanical review, it was identified that in the cities and provinces of the western border region of Iran, medicinal plants such as fennel, wild parsley, shepherd's purse, black cumin, thyme, dandelion, rue, safflower, myrtle, European hornbeam, Kurdistan pistachio, mint, marshmallow root, male orchid, yarrow, agrimony, nettle, bitter herb, verbena, horsetail, periwinkle, marigold, saffron, wild thyme, savory, rhubarb, and eastern chamomile are commonly used for managing, controlling, and treating menstrual pain. Notably, the highest diversity of plant species was observed in the regions of Behbahan, Khuzestan, and Zrewar, Kurdistan. Leaves were the most commonly used plant part, and the Asteraceae and Lamiaceae families presented the highest number of species, indicating the rich diversity of medicinal and traditional plant applications.
Conclusion: The findings of this study demonstrate that the local communities in the western border region of Iran possess extensive knowledge regarding the use of medicinal plants for alleviating menstrual pain. Documenting and scientifically exploring this knowledge could lay the groundwork for the development of effective and natural herbal medicines in the domain of women’s health.

Abstract Cancer is a catastrophic illness with a significant worldwide fatality rate, anticipated to rise in the next years. Contemporary treatment modalities, including chemotherapy and radiation therapy, include constraints such as adverse effects, inconsistent efficacy, elevated expenses, and restricted accessibility. Bacteriophages have arisen as multifaceted instruments in bioengineering, with significant promise in tissue engineering, vaccine formulation, and immunotherapy. Bacteriophages are being used extensively in several fields of biotechnology and medicine, with cancer treatment being the most compelling application. Numerous studies are increasingly validating the effectiveness and safety of phage-based vectors as systemic delivery vehicles for therapeutic genes and medicines in cancer treatment. Moreover, the genetic composition of phages may be used for the creation of innovative DNA vaccines and antigen display systems, since they provide a highly structured and repeated presentation of antigens to immune cells. Bacteriophages have created novel opportunities for the precise targeting of certain molecular determinants in cancer cells. Phages may serve as anticancer agents and as carriers for imaging compounds and medicines. This article introduces bacteriophage and examines the performance of bacteriophages and bacteriophage engineering in targeted cancer treatment.

Abstract Breast cancer is responsible for more than 2.3 million newly diagnosed cases each year, according to the statistics. A hormonal imbalance, which is defined by unregulated activity of estrogen and progesterone, is often the cause of this type of cancer. It has become easier to handle patients who have HR+ breast cancer, particularly in women who have both advanced and early-stage disease, as a result of the deployment of estrogen-blocking hormone treatment. The permissiveness of tamoxifen, which was the first selective estrogen receptor modulator (SERM) to be commercialized, made it possible for more hormonal therapies to be developed. The cornerstone of breast cancer treatment is comprised of aromatase inhibitors (AIs), selective estrogen receptor degraders (SERDs), and cyclin-dependent kinase inhibitors (CDK) 4/6. These three types of drugs ultimately lead to improved patient outcomes. On the other hand, the inherent or acquired resistance of cancers to hormone therapy continues to be a serious cause for concern. Alterations in the genetic makeup of the tumor, as well as the activation of alternate pathways, make this situation even worse. The increasing development of molecular biology, precision medicine, and targeted therapies, on the other hand, is pointing to a new strategy for dealing with these problems. The purpose of this study is to investigate prospective treatment options and to shed light on the significant role that hormone therapy plays in the management of HR-positive breast cancer.

Abstract Background: Menopause comes along with a set of hormonal and physiological changes that can change cardiovascular responses during surgeries, along with altering pain perception. This research intends to analyze pain intensity during and after anesthesia and changes in hemodynamics in pre- and post-menopausal women during elective abdominal hysterectomy under general anesthesia.
Methods: Elective surgery patients, in this case, were 88 in number, with each division having 44 patients (before menopause and after). Women in each group were defined as premenopausal (n=44) and postmenopausal (n=44) in equal proportion. Other metrics looked at were Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), also known as SpO₂. Patients’ heart rate and SpO₂ were checked during the surgery and after the surgery as well. Pain was assessed with the use of standardized scale methods, and participants were questioned on the pain felt during the post-operative period.
Results: While the premenopause cohort showed lower fluctuations in sensitivity to changes in SBP, DBP, and HR during and after anesthesia, the Postmenopause cohort exhibited the opposite (p<0.05). In each group, the SpO₂ levels were maintained within normal limits and showed no significant group differences. In the postoperative period, the pain score was significantly higher in the postmenopausal group with lower pain tolerance and a higher requirement for analgesic treatment. Spoken demographics such as age, body mass index (BMI), and other associated conditions showed a moderating influence on the hemodynamic response and pain outcomes.
Conclusion: Following menopause, diminished vascular adaptability, along with increased sympathetic tone and decreased central pain modulatory control due to lack of estrogen, might explain the instability of hemodynamics and increased postoperative pain. These observations could help in the formulation of appropriate anaesthetic techniques and postoperative pain relief policies in relation to the reproductive status of women.

Abstract Polycystic ovary syndrome (PCOS) is a common infertility disorder, affecting a significant proportion of the global population. This syndrome has been one of the most controversial entities in gynecological endocrinology for many years. Both genes and the environment contribute to PCOS. Obesity, exacerbated by poor dietary choices, and physical inactivity, worsens PCOS in susceptible individuals. PCOS is a complex and heterogeneous disorder characterized by hyperandrogenemia, hyperinsulinemia, insulin resistance, and chronic anovulation. Many candidate genes have been identified to be one of the causes of PCOS. Different studies have been carried out to find the genetic correlation of PCOS. It is essential to carry out such studies that identify the clear cause of PCOS and its genetic association and hormonal disbalance. Currently, PCOS is considered a polygenic trait that might result from the interaction of susceptible and protective genomic variants and environmental factors, during either prenatal or postnatal life.

Abstract Background: Lung cancer is the first cause of cancer deaths in the world. Pemetrexed is an antifolate drug used as a first or second-line in the treatment of advanced non-small cell lung cancer (NSCLC) patients. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in a folic acid metabolic pathway and a central role in clinical response to pemetrexed. The aim of this study was to investigate the association between rs1801133 polymorphism and the overall survival of metastatic NSCLC patients.  
Methods: Thirty-four patients with metastatic lung cancer were treated with pemetrexed-based regimen at Rasoul Akram Hospital, Tehran, Iran. Genomic DNA was extracted from the peripheral blood of patients before initiation of treatment. Genotyping of rs1801133 polymorphism was performed at the National Institute of Genetic Engineering by PCR-RFLP methods. Statistical analysis performed with SPSS software, version 21.0.
 Results: Thirty-four patients were enrolled in this study. 21 patients (62%) were male and 13 (38%) were female. The mean age of the patients was 58.90 years. rs1801133 polymorphism were not significantly associated with survival in patients treated with pemetrexed-based chemotherapy.
 Conclusion: Previous studies have demonstrated that MTHFR polymorphism may predict survival among pemetrexed-based regimen treated advanced non-squamous NSCLC patients. However, in this study, the examined polymorphisms were not associated with patients' survival.

Abstract This review synthesizes and elaborates on current studies examining the neurotoxic effects of microplastics, emphasizing their mechanisms of entry into the central nervous system and their possible involvement in the development of neurodegenerative disorders. The pervasive presence of microplastics in the environment has heightened concerns about their accumulation in biological systems, particularly their capacity to traverse biological boundaries and engage with neuronal tissues. This article seeks to synthesize and critically evaluate the existing scientific literature on microplastic neuroinvasion, concentrating on the mechanisms through which these particles penetrate the blood-brain barrier (BBB) specifically via transcellular, paracellular, or Trojan horse pathways—and their ensuing effects on neuronal homeostasis.

We investigate the physiological and molecular reactions triggered by microplastics, encompassing oxidative stress induction, mitochondrial failure, neuroinflammation, and synaptic disruption. These pathogenic processes may facilitate the onset and advancement of several neurodegenerative disorders, including Alzheimer’s disease, by intensifying amyloid-beta aggregation, tau phosphorylation, and neuroimmune activation. Additionally, we examine the burgeoning epidemiological and experimental evidence associating microplastic exposure with cognitive deterioration and neuronal impairment.

This review offers a thorough analysis of microplastic neurotoxicity by evaluating both in vitro and in vivo studies, with the objective of elucidating the potential neurological hazards associated with these environmental contaminants. We emphasize significant deficiencies in existing research and propose future avenues, encompassing enhanced detection techniques, public health initiatives, and efforts to reduce human exposure to microplastics.

Abstract The aim of this study is to investigate the attitude, beliefs, and perceptions among undergraduate and graduate students toward precession medicine (PM) and pharmacogenomics (PGx) practice. A cross-sectional survey is conducted amongst students from different universities in Bangladesh.The results of the survey showed that the majority of students had a positive attitude towards precision medicine and pharmacogenomics, perceiving it as a means to improve diagnosis and treatment accuracy. Furthermore, many students also expressed a willingness to learn more about precision medicine and pharmacogenomics, suggesting that there is potential for these practices to be utilized in Bangladesh. Particularly in this study, 337 students from life science and relevant programs participated. From this study, it is shown that 84% of graduate students and 74% of undergraduate students thought PM is a promising healthcare model. In addition, 39% of students are highly encouraged to pursue their post-graduation in the subject areas of PGx and PM to support patients. The majority (62%) thought that patient privacy was the ethical concern most closely related to pharmacogenomic testing, while 19% of respondents thought that data confidentiality was the key issue. The results provide insight into the potential of precision medicine and pharmacogenomics in Bangladesh and suggest that further research into the attitudes of healthcare professionals should be conducted in order to take full advantage of the potential of these practices.

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 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 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 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 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.