The role of tryptophan metabolism and tolerogenic dendritic cells in maintaining immune tolerance: Insights into celiac disease pathogenesis Fatemeh Asgari, Mahdi Khodadoust, Abdolrahim Nikzamir, Somayeh Jahani‐Sherafat, Mostafa Rezaei Tavirani, and Mohammad Rostami‐Nejad Wiley AbstractBackgroundIn mammals, amino acid metabolism has evolved to control immune responses. Tryptophan (Trp) is the rarest essential amino acid found in food and its metabolism has evolved to be a primary regulatory node in the control of immune responses. Celiac disease (CeD) is a developed immunological condition caused by gluten intolerance and is linked to chronic small intestine enteropathy in genetically predisposed individuals. Dendritic cells (DCs), serving as the bridge between innate and adaptive immunities, can influence immunological responses in CeD through phenotypic alterations.ObjectiveThis review aims to highlight the connection between Trp metabolism and tolerogenic DCs, and the significance of this interaction in the pathogenesis of CeD.ResultsIt is been recognized that various DC subtypes contribute to the pathogenesis of CeD. Tolerogenic DCs, in particular, are instrumental in inducing immune tolerance, leading to T‐reg differentiation that helps maintain intestinal immune tolerance against inflammatory responses in CeD patients and those with other autoimmune disorders. T‐regs, a subset of T‐cells, play a crucial role in maintaining intestinal immunological homeostasis by regulating the activities of other immune cells. Notably, Trp metabolism, essential for T‐reg function, facilitates T‐reg differentiation through microbiota‐mediated degradation and the kynurenine pathway.ConclusionTherefore, alterations in Trp metabolism could potentially influence the immune response in CeD, affecting both the development of the disease and the persistence of symptoms despite adherence to a gluten‐free diet.
Correlation of IDH1 gene expression error in breast tumor biopsy in patients with invasive ductal carcinoma Behzad Rostami, Sepehr Kahrizi, Batool Ghorbani Yekta, Rezvan Ghadyani, Aliasghar Keramatinia, Seyed Jalil Hoseini, Saeed Karima, Abdol Rahim Nikzamir, Neda Mansouri, Muzi Chen,et al. CMB Association One of the most important cancers in terms of worldwide prevalence is breast tumors, which have been less investigated in correlation with the enzyme Isocitrate Dehydrogenase 1 (IDH1) gene. The aim of this study was that expression of this gene could have significant effects on the progression of metastasis and invasive disease in breast cancer patients. We used the molecular method of RT-PCR with SYBR-Green to analyze breast tumor tissue from patients with metastasis and non-metastasis, the latter confirmed by the pathology department of Shohada-e Tajrish Hospital (serving as a control group). Also, patients population and its relationship with the degree of tumor in the IDH1 gene was investigated. The IDH1 gene has shown high expression in patients with metastatic breast cancer rather than in patients with non-metastatic breast cancer. The metastatic samples were compared with non-metastatic samples for IDH1 mRNA expression. In this research work, 72.5% (29 samples) were up-regulated in comparison to 27.5% of samples (11 samples) that did not exhibit high expression (P=0.000). This study examined the IDH1 gene expression, suggesting that changes in this gene's expression could impact the prognosis of breast cancer. However, further research is needed to draw definitive conclusions.
Exploring fatty acid effects in celiac disease: potential therapeutic avenues Sajjad Bakhtiari, Nastaran Asri, Abdolrahim Nikzamir, Shokoufeh Ahmadipour, Mohammad Rostami-Nejad, and Carolina Ciacci Informa UK Limited BACKGROUND
Fatty acids (FAs) play pivotal roles in modulating inflammatory pathways in celiac disease (CD). The present study explored the relationship between serum FAs levels and the expression of both pro- and anti-inflammatory cytokines in adult and pediatric patients with CD.
METHODS
Serum FA levels in 20 treated CD patients (11 children, 9 adults) and 20 healthy controls (10 children, 10 adults) were analyzed using gas chromatography. Cytokine gene expression (IL-6, TNF-α, IL-10, IL-12, TGFβ, NF-κB) was assessed through quantitative real-time PCR.
RESULTS
Myristoleic acid levels decreased in children with CD (p = 0.03) but increased in adults (p = 0.04). Elevated IL-6 mRNA expression was found in both pediatric (p = 0.01) and adult (p = 0.04) groups. TNF-α expression was significantly higher in adults (p = 0.01). In children, IL-10 mRNA levels positively correlated with palmitic acid (p = 0.01, r = 0.73), and TGF-β correlated with myristoleic acid (p = 0.03, r = 0.63). In adults, IL-10 positively correlated with dihomo-gamma-linolenic acid (p = 0.04, r = 0.68) and negatively with linoleic acid (p = 0.02, r = -0.72). These age-related differences may reflect variations in disease duration, metabolic and developmental factors, dietary intake, and gut microbiota composition.
CONCLUSION
These findings suggest that FAs could be therapeutic targets for improving CD management across different age groups.
Evaluating CD4 and Foxp3 mRNA Expression in Tissue Specimens of Celiac Disease and Colorectal Cancer Patients Nastaran Asri, Ehsan Nazemalhosseini Mojarad, Mohammad Yaghoob Taleghani, Hamidreza Houri, Mahsa Saeedi Niasar, Mostafa Rezaei-Tavirani, Somayeh Jahani- Sherafat, Amirhossein Shahbazkhani, Abdolrahim Nikzamir, Mohammad Javad Ehsani Ardakani,et al. EpiSmart Science Vector Ltd OBJECTIVE
Celiac disease (CD) and colorectal cancer (CRC) are distinct gastrointestinal conditions with a debated association. This study aimed to evaluate the mRNA expression of CD4 and Foxp3 in tissue specimens of CD and CRC patients. The findings can provide valuable insights into the complex connection between these different gastrointestinal conditions.
METHODS
Tissue samples from 100 CRC patients, 50 CD patients, and 50 healthy controls (HCs) were collected. RNA extraction, cDNA synthesis, and quantitative real-time PCR were performed. Statistical analysis was conducted using ANOVA and Pearson's correlation test.
RESULT
CD4 mRNA expression was significantly higher in CRC patients compared to CD patients and HCs (P<0.0001 for both). Foxp3 mRNA expression was significantly higher in CD patients compared to CRC patients and HCs (P<0.0001 for both). Clinicopathological characteristics did not correlate significantly with gene expression levels.
CONCLUSION
This study reveals differential expression patterns of CD4 and Foxp3 mRNA in CRC and CD patients. Upregulated CD4 mRNA suggests its potential role in promoting tumor growth, while increased Foxp3 mRNA expression may reflect an immunosuppressive mechanism in CD pathogenesis. These findings provide insights into the molecular and immunological aspects of CRC and CD, warranting further studies for potential therapeutic strategies.
Investigating the Impact of Vitamin A and Amino Acids on Immune Responses in Celiac Disease Patients Shayan Fallah, Nastaran Asri, Abdolrahim Nikzamir, Shokoufeh Ahmadipour, Amir Sadeghi, Kamran Rostami, and Mohammad Rostami-Nejad MDPI AG Amino acids (AAs) and vitamin imbalances are observed in celiac disease (CD). This study evaluated the plasma profile of vitamin A and AAs and the expression level of IL-2, IL-4, IL-10, IL-12 and TGFβ in CD patients. A total of 60 children and adults with CD and 40 healthy controls (HCs) were included. The plasma profile of Vitamin A and AAs and the mRNA expression levels of target genes were assessed. Active adult patients exhibited a decrease in Vitamin A levels (p = 0.04) and an increase in IL-2 (p = 0.008) and IL-12 (p = 0.007) mRNA expression compared to the HCs. The treated adult patients showed elevated Serine (p = 0.003) and Glycine (p = 0.04) levels, as well as increased IL-12 (p < 0.0001) mRNA expression, and a decrease in Tryptophan (p = 0.04) levels relative to the controls. Additionally, the treated adult patients had higher plasma levels of Threonine compared to both the active (p = 0.04) and control (p = 0.02) subjects, and the increased mRNA expression of IL-4 (p = 0.01) in comparison to the active patients. In active children with CD, the IL-2 mRNA level was found to be higher than in the controls (p < 0.0001) and in the treated children (p = 0.005). The treated children with CD exhibited decreased plasma levels of Tryptophan (p = 0.01) and Isoleucine (p = 0.01) relative to the controls, and the increased mRNA expression of TGFβ (p = 0.04) relative to the active patients. Elevated levels of specific AAs (Serine, Glycine, Threonine) in the treated CD patients suggested their potential to improve intestinal damage and inflammation, while decreased levels of Tryptophan and Isoleucine highlighted the need for dietary intervention.
Potential Molecular Mechanisms of Bisphenol A in Obesity Development Nasrin Amiri-Dashatan, , Zahra Taheri, Niosha Asadi, Farnaz Jahangiri, Nikoo Mozafari, Marzieh Ramandi, Mitra Rezaei, Abdolrahim Nikzamir, Somayeh Jahani Sherafat,et al. Negah Scientific Publisher Bisphenol A (BPA), an endocrine disruptor, is associated with metabolic disorders. However, several studies have suggested that exposure to BPA can cause obesity. It has recently got more attention from scientists as a risk factor for obesity due to its ability to mimic natural estrogens and bind to their receptors. Nonetheless, the molecular mechanism underpinning the environmental etiology of metabolic disorders has not been not fully clarified. In this regard, BPA exposure directly disrupts endocrine regulation, neuroimmune and signaling pathways, and gut microbes, resulting in obesity. In addition, epidemiological studies have revealed a significant relationship between BPA exposure and the development of obesity, although conflicting results have been reported. Therefore, this review summarized the possible role and molecular mechanisms associated with BPA exposure that may lead to obesity based on in vivo and in vivo studies.
Investigating the Mechanism of Arsenic-induced Ferroptosis in the Skin Mehdi Koushki, , Nasrin Amiri-Dashatan, Mitra Rezaei, Fatemeh Montazer, Abdolrahim Nikzamir, Reza Vafaee, Vahid Mansouri, Masoumeh Farahani, ,et al. Negah Scientific Publisher Background: Ferroptosis, an oxidative and iron-dependent cell death, is a new type of regulated cell death. There are few studies on the mechanisms of ferroptosis in the skin and related diseases. Arsenic is shown to induce ferroptosis cell death. This study aimed to decipher the relationship between arsenic exposure and ferroptosis cell death in the skin. Methods: Arsenic-gene interactions were obtained. Then, skin-specific arsenic-gene interactions were screened. Ferroptosis-related genes were identified. Analysis of functional and biological interactions was performed to identify possible mechanisms. Results: The arsenic-gene interactions and the ferroptosis-related genes showed an overlap of 59 genes. Functional enrichment, protein-protein interaction, and transcription factor (TF)/miRNA target gene interaction analyses were used to look into the mechanism of arsenic-induced ferroptosis in the skin. ACTB, CTNNB1, HSPA8, SRC, RACK1, CD44, and SQSTM1 were identified as key proteins. Gene ontology analysis of these proteins indicated the mitochondrial morphology and functionality changes following arsenic-induced ferroptosis in the skin. HIF1A and SP1 TFs regulate a large number of genes compared to other TFs. Ten miRNAs with high interaction with ferroptosis-associated genes were identified. Conclusion: This work investigated the mechanism of arsenic-induced ferroptosis in the skin and identified key genes and regulators, and functional analysis highlighted the role of mitochondria in this skin exposure.
Association of single nucleotide polymorphisms (rs1799883) and gene expression of I-FABP with celiac disease
Suppressive mechanisms induced by tregs in celiac disease Nastaran Asri, , Mohammad Rostami-Nejad, Mohammad Barzegar, Abdolrahim Nikzamir, Mostafa Rezaei-Tavirani, Mohammadreza Razzaghi, Mohammad Reza Zali, , ,et al. Armenian Green Publishing Co.
Radiation therapy in patients with brain cancer: Post-proteomics interpretation Hamid Asadzadeh-Aghdaei, Farshad Okhovatian, Zahra Razzaghi, Mohammadhossein Heidari, Reza Vafaee, and Abdolrahim Nikzamir Maad Rayan Publishing Company Introduction: Radiation therapy (RT) as a common method for cancer treatment could result in some side effects. The molecular investigation is one of the approaches that could assist in decrypting the molecular mechanisms of this incident. For this aim, protein-protein interaction (PPI) network analysis as a complementary study of the proteome is conducted to explore the RT effect on brain cancer after the early stage of exposure prior to the appearance of the skin lesion. Methods: Cytoscape 3.7.2 and its plug-ins were used to analyze the network of differential expression of proteins (DEPs) in the treatment condition, and the centrality and pathway enrichment was conducted by the use of NetworkAnalyzer and ClueGO+CluePedia. Results: A network of 15 DEPs indicated that 6 nodes were key players in the network stability and SERPINC1 and F5 were from the query proteins. The pathways of post-translational protein phosphorylation, platelet degranulation, and complement and coagulation cascades were the most highlighted ones for the central nodes that could be affected in RT. Conclusion: The central proteins of the network of early-stage treatments could have additional importance in the mechanisms of radiotherapy response prior to skin lesions. Introduced biomarkers can be used for the patients’ follow-up. These candidates are worth precise attention for this type of therapy after approving by validation studies.