Immunology and Genetics Journal

Effects of Obesity on Cancer Progression by Affecting the Immune System

Marjan Moallemian Isfahani — 2025-02-18

The prevalence of obesity has been increasing in the last few decades, and it is regarded as one of the major healthproblems in the world. The rising prevalence of obesity in children and adults is a result of eating disordersand the changes related to the modern lifestyle. Obesity alters the adipocytes’ substance secretion, whichaffects the function of the immune system and leads to obesity-induced inflammation and the developmentof obesity-related cancers. Altered chemokines, adipokines, and conditions like insulin resistance are mostlikely related to the impaired immune system in the obesity state. The impaired secretion of adipokines,such as increased leptin and reduction in adiponectin, affects innate immune system antitumor responsesafter long-term exposure. In addition, changes in chemokines and, consequently, the promotion of insulinresistance create an immunosuppressive environment that debilitates the host to fight against tumor growth,progression, and metastasis. Accordingly, it may increase cancer susceptibility in obese individuals. Thereby,it can be concluded that treatment of obesity will greatly affect the improvement of immune system functionand, as a result, may possibly reduce the risk of cancer. The aim of this study is to review the pathwaysresulting in impaired immune system and inflammation and their link to cancer progression in obesity.Several hypotheses have been proposed to have a critical contribution to the development of obesity-relatedcancers, such as the function of cytokines, insulin resistance, and NF-κB and senescence changes in obesity.These hypotheses will be discussed later in this article.

IL-17 in Pneumonia: Cure or Corruption?

Maryam Keyfari — 2025-02-18

As a pro-inflammatory cytokine, IL-17 is important in the immune system against fungal and bacterial in-fections. The IL-17 cytokine family consists of six members that exert their effects by cooperating with fivereceptors that form the IL-17 receptor family. Although IL-17 is mainly a defensive factor, at times, overex-pression of this cytokine will lead to inflammatory and damaging outcomes.Pneumonia is a lower airway disease that can be caused by different agents. In this condition, IL-17 is secret-ed from different cells and can fight against infection or otherwise lead to progression of the disease. Thisarticle reviews the IL-17 role in pneumonia and different inflammatory pathways that it can affect.

A Narrative Review on the Effect of Rituximab on Secondary Humoral Immune Response

Shayan Dasdar — 2025-02-18

Rituximab is a chimeric monoclonal antibody with binding specificity to CD20-positive B lymphocytes. Patients administered rituximab would not have adequate humoral response to the SARS-CoV-2 vaccine. Rituximab can also affect the durability of immunization. Plasma-secreting antibodies and memory B-cells are two major arms of long-term immunity. The role of memory B-cells becomes prominent by decreasing antibody titers over time. The activated memory B cells have CD20 protein on their surface. Investigating the effect of rituximab on other vaccines has demonstrated attenuated recall response. The evidence in this review suggests that we can also expect a deficit of recall response to SARS-CoV-2, making the ritux- imab-treated patients susceptible to reinfection with emerging variants. Therefore, it is better to consider other therapeutic options, use lower rituximab doses, and employ booster vaccines at shorter intervals.

Application of Animal Models to Study Infectious Diseases

Faezeh Ramezani — 2025-02-18

Infectious diseases, which are caused by microorganisms such as bacteria, viruses, fungi, or parasites, can be contracted from other people, the environment, animal contact, or insect bites. Infectious diseases are becoming escalating concerns, mainly due to increasing antibiotic resistance. These disorders remain one of the primary causes of human mortality. Due to the lack of human data on new emerging diseases, ethical values, and the lethal risk of these pathogens, animal models are often recommended for experimental re- search on these diseases. According to the similarities between humans and animals in physiology, genetics, anatomy, availability, ease of handling, and production rate, scientists evaluate different medical problems in animal models before applying their findings to humans. According to the recent advent of the isolation of novel microorganisms, researchers must challenge the infectious ability of microorganisms in the biological system of animal models. An infectious disease animal model attempts to mimic the host-pathogen inter- action. Accordingly, a disease model is defined by both the host and pathogen combination. In this review article, we aimed to discuss various animal models established for studying different infectious diseases.

Toll-like Receptors in Autism Spectrum Disorder

Kimia Kazemzadeh — 2025-02-18

Autism Spectrum Disorder (ASD) is a multifaceted neurodevelopmental condition characterized by diversebehavioral and cognitive challenges. Despite its rising prevalence, the underlying mechanisms remain in-adequately understood. Toll-like receptors (TLRs), as critical components of the innate immune system, areimplicated in neuroinflammatory processes that may contribute to the pathogenesis of ASD. This narrativereview delves into the relationship between TLRs and ASD. Notably, studies reveal an upregulation of TLR4and TLR2 expression in B cells and placental tissues of individuals with ASD, correlating with increasedlevels of pro-inflammatory cytokines such as IL-6 and TNF-alpha. Maternal immune activation (MIA),particularly due to infections during pregnancy, has been shown to trigger TLR-mediated inflammatoryresponses that adversely affect fetal brain development. For instance, maternal cytomegalovirus (CMV)infection leads to heightened expression of TLR4/2 in the placenta, resulting in significant placental in-flammation and altered neurodevelopmental trajectories in offspring. Furthermore, evidence indicates thatindividuals with ASD exhibit impaired immune responses characterized by dysfunctional natural killer(NK) cells and monocytes, which produce excessive pro-inflammatory cytokines upon TLR4 stimulationbut show diminished responses to TLR9 ligands. This immune dysregulation is associated with a shift to-wards a TH2 cytokine profile, complicating the understanding of immune phenotype correlations with ASDsymptom severity. Additionally, TLR3 activation by viral RNA has been linked to behavioral changes inmurine models, underscoring the potential for maternal infections to influence neurodevelopment throughTLR signaling pathways. These findings illuminate the role of TLRs in ASD pathophysiology and suggestthat targeting TLR pathways may offer novel therapeutic avenues for intervention in this complex disorder.

Multiplex Genome Modifications of Astrocytes Through CRISPR Dead Cas9: A Novel Candidate Therapy for Chronic Ischemic Stroke

Melika Lotfi — 2025-02-18

A stroke is an enervating injury to the brain that occurs from a stoppage in blood supply (ischemic stroke) or bleeding (hemorrhagic) in a hemisphere of the brain. Globally, about 10 million deaths per year are recorded because of stroke. There has been no definitive FDA-approved treatment for chronic ischemic stroke without any side effects so far. Therefore, the search for new therapies is necessary. In this paper, after investigating several studies online, on Google Scholar, PubMed, and Scopus, we hypothesized improving the complications of chronic ischemic stroke in induced Sprague-Dawley rat model by intraluminal suture middle cerebral artery occlusion (MCAo), utilizing the combination of cell therapy and gene therapy. A new version of astrocytes is proposed by making some changes in their genome. To gain this goal, a gene profile including IL-38 (the most modern anti-inflammatory agent, which barricades inflammatory re- sponse factors), BRAG-1 (an anti-apoptotic gene from BCL-2 family), IL-38 and BRAG-1’s complementary scaffold RNAs for their expression by deadCas9 (dCas9), complementary scaffold RNAs of LZK and MST-1 for their deletion, and deadCas9 gene is used. Based on studies and documents, we hypothesized using modified astrocytes by dCas9, which is the most accurate genome-editing technology

Investigation of Serum CRP Levels in People with Recurrent Aphthous Stomatitis

Behnam Khazaei — 2025-02-18

Background: Recurrent Aphthous Stomatitis (RAS) is a common, painful condition marked by recurrentoral ulcers, impacting quality of life. Its etiology is unclear but involves genetics, immune dysregulation, andenvironmental factors. This study explores the link between serum C-reactive protein (CRP) levels and RASto assess the role of systemic inflammation.

Methods: In a cross-sectional study design, we enrolled 26 participants diagnosed with RAS according toestablished diagnostic criteria alongside a control group of 26 healthy individuals matched for age and gen-der. Serum CRP levels were quantified using enzyme-linked immunosorbent assay (ELISA) methods, anddemographic, clinical, and lifestyle data were collected through structured questionnaires. We employedstatistical analyses, including t-tests and regression models, to assess the association between serum CRPlevels and the frequency and duration of RAS.

Results: Our findings reveal significantly elevated serum CRP levels in individuals with RAS compared tohealthy controls (p<0.04), indicating a potential link between systemic inflammation and the pathophysiol-ogy of RAS. Additionally, elevated CRP levels were associated with increased ulcer severity and prolongedhealing time. Multivariate analyses further demonstrated that serum CRP could serve as an independentpredictor of RAS severity, highlighting its potential role as a biomarker for disease activity.

Conclusion: Our investigation provides compelling evidence that systemic inflammation, as indicated byelevated serum CRP levels, is associated with RAS.

A Pilot Study of FOXP3 Gene (rs2232365, rs3761547, and rs3761548) Mutations in Migraine Patients

Murugesan Arumugam — 2025-02-18

Background: The role of immune dysfunction in migraine pathogenesis is currently debated. Migraines are common among family members, yet no significant gene polymorphisms have been identified to date. However, our earlier clinical study findings led us to hypothesize that migraine initiation could be influenced by genes that regulate immune function, specifically Forkhead box P3 (FOXP3). To test this hypothesis, we conducted a pilot study targeting FOXP3 Single Nucleotide Polymorphisms (SNPs), commonly associated with other autoimmune conditions in patients with migraine.

Materials and Methods: The minimum sample size required for this study was determined by considering the mean difference in Regulatory T cells (Tregs) reduction reported in previous studies. Twenty participants (10 patients and 10 controls) were recruited for this study. Familial clinical history was collected for pedigree analysis and the samples were tested for the targeted SNPs.

Results: The prevalence of the AG genotype for rs2232365 was 50% among patients and 20% among controls (OR: 4.0, CI: 0.54-29.09, p=0.17). Regarding rs3761547, the AG genotype was observed in 60% of patients and 10% of controls (OR: 13.5, CI: 1.19-152.2, p=0.03), whereas the AC genotype was found in 70% of patients and only 10% of controls (OR: 21.0, CI: 1.77-248.1, p=0.01).

Conclusion: Our preliminary analysis suggested a possible association between FOXP3 variance and migraine predisposition, particularly with the AG and AC genotypes at the rs3761547 and rs3761548 SNPs, respectively. These findings highlight the importance of conducting a more extensive FOXP3 mutation study in a larger cohort of migraine patients