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 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.

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.

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.

Abstract Aim: Oxidative stress is one of the main factors has been implicated in pathophysiology of cataracts. Superoxide dismutase (SOD) can prepare the first line of defense versus detrimental reactive oxygen species (ROS) and Sirtuin (SIRT) confers protection against oxidative stress and retinal degeneration. Correlation of SOD1-50bp ins/del and SIRT1-rs7895833 polymorphisms with risk of cataracts is not studied currently. Therefore, we aimed to explore possible relationship between SOD1 (50bp ins/del) and SIRT1 (rs7895833) polymorphisms with the risk of cataracts in Iranian population. 
Methods: Our study design consisted of 200 patients with age-related cataracts and 200 healthy individuals as a control group. After DNA extraction, the identification of polymorphisms was conducted using PCR-based methods and data analysis was done by SPSS software. 
Results: A significant difference in SOD1 DD genotype distribution was observed between studied groups (OR: 3.42, P:0.037), the D allele was more frequent in patients in comparison with controls (OR: 1.68, P:0.009). Also, in the dominant genetic model for the D allele (comparison between ID+DD vs. II), ID+DD genotypes increased the risk of cataracts (OR: 1.62, P: 034). The association between SIRT1-rs7895833 polymorphism and cataract was significant in the AG genotype (OR: 2.37, P<0.001) and G allele (OR: 1.97, P<0.001). The SIRT1-1 polymorphism increased the risk of cataracts in the dominant tested inheritance model (OR: 2.34, P<0.001). In the combined analysis of two polymorphisms, there is an additive effect of the high-risk putative alleles about the risk of cataracts. Risk estimation according to the number of high-risk alleles showed that χ2 for linear trend for 0, 1, 2, 3 and 4 putative high-risk alleles is equal to 20.10 (P<0.001). 
Conclusion: The results showed that for the first time, SIRT1 rs7895833 and SOD1-50bp ins/del gene variations had additive effects on the risk of cataracts.

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

Abstract There were more than thirty-eight million HIV infections worldwide. Combination antiretroviral therapy (cART) has progressed to the point where invisible viral loads are now feasible, and HIV carriers frequently lead almost everyday lives with considerably greater average life expectancies than in the past. However, there is still no cure for the disease. Even though the ailment usually advances to a chronic state, an individual's unique course of progression may differ significantly from the average and manifest distinctively for each patient. This diversity begs whether a typical treatment strategy is appropriate for a patient.
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Abstract The enormous genetic variety of the viral population harbored by the patient and the large volume of therapeutic alternatives characterize HIV therapy. Each patient and period has its viral population. The enormous number of therapy possibilities makes selecting an ideal or near-optimal therapy challenging, especially among therapy-experienced patients. Over the last decade, computer-based medication selection that measures viral resistance to pharmaceuticals has become a norm for HIV patients. We explore the qualities of available systems and the field's viewpoints.

Abstract Objectives: Diabetes mellitus type 1 (T1DM), which is also an autoimmune disorder, can coexist alongside other types of autoimmune diseases. This study aimed to investigate the possibility of a subclinical association between diabetes disease and autoimmune thyroid dysfunction. The clinical condition of the patient and their approach to managing their diabetes were specifically considered when deciding whether or not the patient had autoantibodies.
Methods: This study included sixty individuals who were diagnosed with diabetes type 1. (thirty males and thirty women, with a mean age of 21.04 years) and 30 healthy controls (12 males and 18 females).
Results: Diabetics had considerably greater serum IL-10, IL-6, and TNF-α levels than healthy controls. Stepwise regression indicated significant positive correlations between IL-10, IL-6, and TNF-α with these antibodies and strong inversed relationships between IL-6 and Anti-TPO, Anti-TG, antibodies.
. No matter if the antibodies were present or how severe they were, this held true. The study's findings lend credence to the idea that people with type 1 diabetes should have their thyroid antibodies and function checked.
Conclusions: Thyroid antibodies were most common among type 1 diabetics aged 21–35, according to our study (Anti-TPO and Anti-TG). IL-10, IL-6, and TNF-α levels in diabetic patients and controls were significantly different (P<0.01). IL-10, TNF-α, HbA1C, and body mass index positively correlated with thyroid antibodies, except for IL-6. Thyroid antibodies and functional abnormalities should be tested often in type 1 diabetics due to the high occurrence of thyroid autoimmune illnesses.