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Iranian Journal Of Allergy, Asthma, And Immunology[JOURNAL]

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MiR-425-5p Mediation of Malignant Behavior and Immune Escape of Cervical Cancer Cells by Targeting NCAM1.

Xiang M, Yu Y, Gao Q … +1 more , Xing J

Iran J Allergy Asthma Immunol · 2025 Oct · PMID 41266268 · Publisher ↗

MicroRNA (miR)-425-5p is used as a molecular biomarker to identify cervical cancer (CxCa). However, few studies have examined the miR-425-5p-based modulation of the vital activities of CxCa cells. The levels of neural ce... MicroRNA (miR)-425-5p is used as a molecular biomarker to identify cervical cancer (CxCa). However, few studies have examined the miR-425-5p-based modulation of the vital activities of CxCa cells. The levels of neural cell adhesion molecule 1 (NCAM1) and miR-425-5p in CxCa tissues and cells were tested using western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) tests. CxCa cells' malignant phenotype was examined through clone formation tests, and transwell tests. CD8+T cells were co-cultured with CxCa cells and then analyzed for apoptosis rates and the expression of activation proteins (granzyme B (GZMB) and perforin) as well as immune factors (tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)) using flow cytometry, western blot, and enzyme-linked immunosorbent assay (ELISA) methods. Finally, in nude mouse experiments, the tumor size was measured for subcutaneous tumors, and the expression of CD8+T cell-related factors was detected. The NCAM1 and miR-425-5p were down-regulated and up-regulated in CxCa tissue and cells, respectively. After silencing miR-425-5p, CxCa cells showed attenuation in vitality, clone formation rate, and their capacities to migrate, penetrate, and evade immune responses. NCAM1 was targeted and silenced by miR-425-5p. When NCAM1 was silenced, it partially counteracted miR-425-5p's inhibitory effects on the immune escape and proliferation. In nude mice, the tumor size and weight decreased after silencing miR-425-5p, and levels of CD8, IFN-γ, TNF-α, perforin, and GZMB were elevated. However, these changes were reversed when NCAM1 was silenced. In conclusion, miR-425-5p mediates the biological behavior and immune evasion of CxCa cells by regulating NCAM1.

Abscisic Acid Regulates Immune-inflammatory Responses to Induce Neuroprotection in Spinal Cord Injury: Insights from Gene Expression and Network Analysis.

Rezaeezade Roukerd M, Dogani M, Motaghi S … +1 more , Abbasnejad M

Iran J Allergy Asthma Immunol · 2025 Oct · PMID 41266267 · Publisher ↗

Spinal cord injuries (SCI) lead to complex primary and secondary damage that disrupts neural function. Current treatments are often insufficient and unable to fully repair spinal cord injuries, highlighting the urgent ne... Spinal cord injuries (SCI) lead to complex primary and secondary damage that disrupts neural function. Current treatments are often insufficient and unable to fully repair spinal cord injuries, highlighting the urgent need for new medicines and innovative therapies. This study aimed to evaluate the therapeutic potential of abscisic acid (ABA) in SCI by examining its effects on immune-inflammatory genes' expression in rats. This phytohormone possesses anti-inflammatory and neuroprotective properties, rendering it a potential agent for reducing secondary damage following spinal cord injury. Additionally, we performed protein-protein interaction (PPI), pathway enrichment, functional annotation, and gene ontology (GO) analyses to gain a comprehensive understanding of the functions of the affected genes. Based on the results, SCI led to changes in the expression of immune/inflammation-related genes in rats. However, the administration of ABA alleviated the effects. ABA downregulated proinflammatory genes (IL-6, IL-1β, MCP, TLR2, TLR4) and neural signaling components (NMDA, AMPA, NK1R), while upregulating adrenergic receptors (ADRA1A, ADRB1) and a gamma-aminobutyric acid receptor (AGBRA2). PPI analysis identified FOS, IL-1β, IL-6, MMP9, and TLR4 as crucial nodes in the network, exhibiting the highest degree of interaction. Functional analyses revealed potential impacts on cellular responses, metabolic processes, and synapse-associated extracellular matrix components. Notably, these genes were enriched in inflammatory signaling pathways according to KEGG analysis. These findings suggest that ABA has a significant modulatory effect on gene expression following SCI, particularly in reducing inflammation and immune responses, thereby highlighting its potential as a novel therapeutic agent for SCI.

Investigating Novel Biomarkers in Endometrial Cancer - A Study on RT-qPCR and Immunohistochemistry.

Li R, Yan Y, Liu F … +4 more , Gao X, Fu X, Hu L, Li Y

Iran J Allergy Asthma Immunol · 2025 Oct · PMID 41266266 · Publisher ↗

This study aimed to investigate the expression patterns of HOXB9, DLX5, NGR1, and GATA6 in endometrial cancer tissues compared to adjacent non-cancerous tissues. Using RT-qPCR and immunohistochemistry, the researchers fo... This study aimed to investigate the expression patterns of HOXB9, DLX5, NGR1, and GATA6 in endometrial cancer tissues compared to adjacent non-cancerous tissues. Using RT-qPCR and immunohistochemistry, the researchers found significant upregulation of HOXB9, DLX5, and NGR1, and downregulation of GATA6 in endometrial cancer samples. The biomarker expression levels correlated with clinicopathological features, and survival analysis revealed that high expression of HOXB9, DLX5, and NGR1 was associated with poorer prognosis, while high GATA6 expression indicated better outcomes. These findings suggest that these biomarkers may play crucial roles in endometrial cancer development and progression, highlighting their potential as diagnostic, prognostic, and therapeutic targets.

Measuring Dedicator of Cytokinesis 8 (DOCK8) Expression as a Flow Cytometry Biomarker for DOCK8 Deficiency Detection.

Moradi M, Yousefpour Marzbali M, Nazari N … +4 more , Chavoshzadeh Z, Mahdaviani SA, Sadeghi-Shabestari M, Rezaei N

Iran J Allergy Asthma Immunol · 2025 Oct · PMID 41266265 · Publisher ↗

  The autosomal recessive form of hyperimmunoglobulin E syndrome (AR-HIES), caused by mutations in the DOCK8 (Dedicator of Cytokinesis 8) gene, presents a wide range of clinical manifestations and phenotypically overlaps...   The autosomal recessive form of hyperimmunoglobulin E syndrome (AR-HIES), caused by mutations in the DOCK8 (Dedicator of Cytokinesis 8) gene, presents a wide range of clinical manifestations and phenotypically overlaps with several types of combined immunodeficiency disorders characterized by elevated serum IgE levels. Due to the high rates of morbidity and mortality, as well as the potential curability through hematopoietic stem cell transplantation (HSCT), early and accurate differential diagnosis of this syndrome is crucial for optimal management and improved prognosis. Flow cytometry tests can be beneficial for early diagnosis of many inborn errors of immunity (IEIs), including this syndrome. This study, conducted for the first time on Iranian patients, investigated the expression of the DOCK8 protein. DOCK8 expression was assessed by flow cytometry in 14 patients (6 males and 8 females) with a clinical diagnosis of DOCK8 deficiency. The diagnosis was ultimately confirmed through genetic testing. The results showed that DOCK8 expression in patients was significantly lower compared to the healthy control group. Flow cytometric evaluation of DOCK8 protein expression offers a rapid and efficient diagnostic method with a sensitive detection range suitable for many cases. This approach can facilitate the diagnosis of DOCK8 deficiency, thereby enabling timely and effective disease management.

Transcription Factor and Cytokine Profiles in Peripheral Blood T Helper Cells in Patients with Idiopathic Pulmonary Fibrosis.

Dalil Roofchayee N, Heshmatnia J, Jamatti H … +3 more , Varahram M, Adcock IM, Mortaz E

Iran J Allergy Asthma Immunol · 2025 Oct · PMID 41266264 · Publisher ↗

Idiopathic pulmonary fibrosis (IPF) is a severe lung disease with a poor prognosis, characterized by immune cell activation. The role of T helper (Th) cell transcription factors in IPF pathogenesis remains unclear. In th... Idiopathic pulmonary fibrosis (IPF) is a severe lung disease with a poor prognosis, characterized by immune cell activation. The role of T helper (Th) cell transcription factors in IPF pathogenesis remains unclear. In this study, we investigated Th cell transcription factors and related cytokines in IPF patients. Twelve IPF patients and eight healthy controls (HC) were enrolled in this pilot study. Serum levels of fibrosis-associated mediators (Interferon-inducible protein 10 (IP-10), tumor necrosis factor-α (TNF-α), tumor growth factor-β (TGF-β), CXCL-8, interferon-γ (IFN-γ)) were measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometry assessed Th transcription factors T box transcription factor (T-bet,), GATA-binding protein 3 (GATA-3), Retinoic acid-related orphan recepto (ROR-γt), forkhead box P3 (FOXP3)) and intracellular cytokines (IL-4, IL-17). SerumTGF-β, CXCL-8, TNF-α, and IFN-γ were significantly elevated, while IP-10 (pT-bet, GATA3, ROR-γt, or FOXP3 were observed. Positive correlations were found between T-bet and GATA3, IL-4, ROR-γt, and TNF-α expression with age, while FOXP3 expression negatively correlated with age. T-cell transcription factors were unchanged in IPF despite changes in inflammatory protein expression. Reduced IP-10 may serve as a potential marker.

Relationship between the Effects of Different Parenteral Nutrition Durations of Two Intravenous Fat Emulsions on Intravenous Nutrition-related Immune Status and Clinical Outcomes in Premature Infants.

Yao L, Huang F

Iran J Allergy Asthma Immunol · 2025 Oct · PMID 41266263 · Publisher ↗

Premature infants with immature gastrointestinal tracts rely on parenteral nutrition (PN) to meet nutritional and energy requirements for growth. In this study, we compared the nutrition-related immune status of prematur... Premature infants with immature gastrointestinal tracts rely on parenteral nutrition (PN) to meet nutritional and energy requirements for growth. In this study, we compared the nutrition-related immune status of premature infants receiving SMOF emulsions (multiple oil-fat emulsions) versus those receiving MCT/LCT emulsions (medium-/long-chain triglyceride emulsions) at different times during PN, and we analyzed the relationship between immune function and clinical outcomes. Sixty premature infants from Dongxihu District People's Hospital, recruited between September 2023 and September 2024, were divided into an observation group and a control group. The observation group received SMOF emulsions, while the control group received MCT/LCT-containing emulsions. We compared immune function, clinical outcomes, and complications between the two groups at different PN timings. The effects of fat-emulsion type on immune indices and their relationship with clinical outcomes were assessed using logistic regression and ROC analysis. The clinical data of the preterm infants in both groups were similar. Immune function and clinical outcomes were better in the observation group than in the control group, and the complication rate was lower. Logistic and ROC analyses revealed that the type of fat emulsion was closely related to immune indices, and these immune indices were highly correlated with clinical outcomes. Both interventions improved immunity in preterm infants, with better results in the observation group than in the control group. The use of SMOF emulsions was superior to MCT/LCT-containing emulsions in preterm infants requiring long-term PN, and this immune improvement significantly optimizes clinical outcomes.

Relative and Absolute Regulatory T Cells in Preterm Neonates with Necrotizing Enterocolitis.

Cheng Y, Tai Y, Ge L … +3 more , Qiu X, Wang J, Chang Y

Iran J Allergy Asthma Immunol · 2025 Oct · PMID 41266262 · Publisher ↗

The objective of this study was to compare the concentrations of relative and absolute regulatory T cells (Tregs) in preterm neonates diagnosed with necrotizing enterocolitis (NEC) with those in the control group. The st... The objective of this study was to compare the concentrations of relative and absolute regulatory T cells (Tregs) in preterm neonates diagnosed with necrotizing enterocolitis (NEC) with those in the control group. The study consisted of 60 preterm neonates, 30 with NEC and 30 without NEC. Blood samples were obtained and processed for the enumeration of Treg cells by multiparameter flow cytometry with markers such as CD4, CD25, and FOXP3, and the activation markers CD45RA, CD45RO, HLA-DR, and CTLA-4. There were no significant differences in gestational age, body weight, Apgar score, delivery mode, or incidence of maternal infection between the NEC group and the control group. The relative Treg percentage (% of CD4+ T cells) in the NEC group was 7.5 ± 1.2%, which was significantly lower than that in the control group (9.8 ± 1.5%). Compared with that in the control group, the absolute Treg count in the NEC group showed the same trend, and the total CD4+ T-cell count decreased significantly. The percentage of naive Tregs (% of Tregs) was significantly higher, whereas those of memory Tregs (% of Tregs), Ki-67+ (% of Tregs), and CD39+ (% of Tregs) cells were significantly lower. Tregs may be activated more as the severity of NEC increases, and the elevated levels of interleukin (IL)-10 in NEC may reflect attempts at an effective anti-inflammatory response to the proinflammatory effects of IL-6 and TNF-ɑ. Treg pathways may hold promise for NEC prognosis, although additional samples should be evaluated to validate these results.   Keywords: ; ; ; ;

Expression of Serum Immune Inflammatory Factors in Children with Suppurative Tonsillitis Caused by Adenovirus Infection and Its Correlation with Adenovirus Pneumonia.

Lei D, Liu Y, Liu M

Iran J Allergy Asthma Immunol · 2025 Oct · PMID 41266261 · Publisher ↗

Adenovirus infection is a common cause of pediatric respiratory disease, often misdiagnosed as a bacterial infection. This study compared immune-inflammatory markers in children with adenovirus- vs bacterial-induced supp... Adenovirus infection is a common cause of pediatric respiratory disease, often misdiagnosed as a bacterial infection. This study compared immune-inflammatory markers in children with adenovirus- vs bacterial-induced suppurative tonsillitis and evaluated their correlation with adenovirus pneumonia. A retrospective study of 275 children (145 with adenovirus, 130 with bacterial infections) admitted to The First People's Hospital of Changde, China (January-June 2019), was conducted. Laboratory markers (white blood cell [WBC] count, C-reactive protein [CRP], serum amyloid A [SAA], procalcitonin [PCT], heparin-binding protein [HBP], tumor necrosis factor-alpha [TNF-α], and interleukin 6 [IL-6]) were analyzed. Adenovirus cases were stratified by pneumonia status (58 with pneumonia, 87 without pneumonia) via chest computed tomography. Compared with the bacterial group, the adenovirus group had lower WBC counts (14.97 [1.37] vs 18.86 [2.65] ×109/L), CRP levels (15.26 [3.44] vs 26.36 [3.18] mg/L), and PCT levels (15.06 [2.12] vs 42.53 [4.58] ng/L) but higher SAA levels (216.75 [39.23] vs 136.55 [28.66] mg/L). Among children with adenovirus, those with pneumonia had elevated SAA (236.39 [38.67] vs 203.65 [33.95] mg/L), HBP (44.30 [8.93] vs 35.62 [6.77] ng/mL), TNF-α (731.52 [99.21] vs 604.21 [95.53] ng/L), and IL-6 (96.86 [17.63] vs 76.55 [15.50] ng/L) levels. A combination of SAA, HBP, TNF-α, and IL-6 predicted pneumonia with an area under the curve of 0.927 (sensitivity, 87.93%; specificity, 88.51%). SAA, HBP, TNF-α, and IL-6 are strongly associated with adenovirus pneumonia, and their combined measurement improves diagnostic accuracy.

Comparing Basophil Activation Test and Specific IgE Assay in the Diagnosis of Allergy to Penicillin G and Ibuprofen.

Shakerin P, Shokouhi Shoormasti R, Fazlollahi MR … +13 more , Jafari M, Delkhah M, Bahraini P, Moradi L, Mahloojirad M, Movahedi M, Sadri H, Fallahpour M, Shafiei A, Zandieh F, Tavakol M, Tajdini M, Pourpak Z

Iran J Allergy Asthma Immunol · 2025 Oct · PMID 41266260 · Publisher ↗

The risks associated with in vivo tests in the diagnosis of immediate drug hypersensitivities result in evaluating alternative in vitro tests, such as the Basophil Activation Test (BAT). This pilot study aimed to set up... The risks associated with in vivo tests in the diagnosis of immediate drug hypersensitivities result in evaluating alternative in vitro tests, such as the Basophil Activation Test (BAT). This pilot study aimed to set up a BAT and compare it with a specific Immunoglobulin E (sIgE) assay for penicillin G and Ibuprofen in patients with immediate hypersensitivity to β-lactams or nonsteroidal anti-inflammatory drugs (NSAIDs). Eleven subjects with a clear history of immediate hypersensitivity to one of the β-lactams (n=5), the NSAIDs (n=3), or both (n=3) entered this study. BAT and sIgE assays were performed regarding the patient's history. The most frequent manifestations were angioedema, shortness of breath, urticaria, and nausea. Eight patients had anaphylactic reactions. The results presented a positive BAT for penicillin G and one for Ibuprofen. Moreover, three patients with a history of the β-lactams reaction demonstrated positive sIgE to β-lactams in the ImmunoCAP. Despite a lack of agreement between the positive results of the BAT and sIgE assay, five patients were identified by one of these methods. Despite positive BAT and sIgE results in two and three patients, respectively, the risks, high cost, and time-consuming nature of drug challenges render these tests valuable for reducing the number of patients who are candidates for a drug challenge.

Comparison of Oral Desensitization with Heated Cow's Milk Products with Conventional Desensitization Method in Children with Cow's Milk Allergy.

Movahedi M, Bahraminia E, Amirzargar A

Iran J Allergy Asthma Immunol · 2025 Oct · PMID 41266259 · Publisher ↗

Cow's milk allergy (CMA) is one of the most prevalent Immunoglobulin E (IgE)-dependent food allergies in children. Currently, the only accepted treatment for food allergy is avoiding the relevant allergen. The purpose of... Cow's milk allergy (CMA) is one of the most prevalent Immunoglobulin E (IgE)-dependent food allergies in children. Currently, the only accepted treatment for food allergy is avoiding the relevant allergen. The purpose of this study is to investigate the immunological changes following the consumption of heated cow's milk products compared to the usual method of oral desensitization in children aged over two years old with cow's milk allergy. In a prospective double-blind clinical trial study, 25 children aged two years and older with a definite diagnosis of IgE-dependent cow's milk allergy referred to the allergy clinic of the Children's Medical Center from 2016 to 2017 were enrolled. The eligible patients were randomly divided into two groups: the first group was desensitized with raw milk (normal desensitization: n=13), and the second group was desensitized with heated cow's milk products (intervention group, n=12). The mean ages in the raw milk group and heated milk group were 3.92±1.44 and 4.50±1.73 years, respectively. The rate of anaphylaxis in the heated milk group was higher than in the raw milk group (50% vs. 15.4%), although the incidence of urticaria and angioedema was not significantly different between the two groups. The mean concentration of serum IgE in the two groups decreased after desensitization compared to before, although there was no significant difference between the two groups. The increase in the number of CD4+Foxp3+ and CD4+ CD25+ cells was less in the heated milk group than the raw milk group, but this difference was not statistically significant. Additionally, the number of eosinophil cells was higher in the heated milk group than in the raw milk group, but this difference was not statistically significant difference. We concluded that the changes in the level of eosinophil, IgE, and regulatory T cells in the conventional desensitization group were not significantly different compared to desensitization with heated milk. Further multicenter studies with a higher sample size are recommended to confirm these results.

Immunomodulatory Effects of Stem Cell Therapy in Liver Fibrosis: A Systematic Review.

Rahimi S, Derakhshani A, Alifarsangi A … +3 more , Shakeri Goki MH, Khoshnazar SM, Shahrokhi N

Iran J Allergy Asthma Immunol · 2025 Oct · PMID 41266258 · Publisher ↗

Liver fibrosis is known as a condition characterized by chronic inflammation and excessive extracellular matrix deposition that causes cirrhosis and liver failure. Stem cell therapy is a promising strategy for the manage... Liver fibrosis is known as a condition characterized by chronic inflammation and excessive extracellular matrix deposition that causes cirrhosis and liver failure. Stem cell therapy is a promising strategy for the management of liver fibrosis because it not only improves tissue regeneration but also modulates by immunomodulatory mechanisms. This systematic review aimed to evaluate the immunoregulatory effects of stem cells in both experimental models and clinical studies of liver fibrosis. A total of 29 studies were included, comprising several stem cell sources, including bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord-derived MSCs (UC-MSCs), adipose tissue-derived MSCs (AT-MSCs), and stem cells from human exfoliated deciduous teeth (SHED), among others. Studies reported that stem cells could decrease proinflammatory cytokines (e.g., TNF-α, IFN-γ, IL-17) and fibrosis-related markers, while increasing levels of anti-inflammatory cytokines (e.g., IL-10, IL-4) and regulatory immune cells such as Tregs (regulatory T cells). Stem cells could affect immune homeostasis via modulating in macrophage polarization, T cell subsets, and B cell activity, resulting in attenuated fibrotic progression and improved liver function. Despite variability in cell types, routes of administration, and fibrosis models, the results support the potential of stem cell therapy to reform the hepatic immune microenvironment. However, more standardized protocols and clinical validations are required. This study emphasizes the immunomodulatory potential of stem cells as a therapeutic method in liver fibrosis. It brings a clear view into their mechanisms of action and the foundation for future translational applications.

Immunological Insights into the PI3K-Akt Pathway in Osteoporosis and Periodontitis: A Proteomic and Metabolomic Approach.

Qi J, Pang Y, Yang Q … +3 more , Wang Y, Hou D, Wang J

Iran J Allergy Asthma Immunol · 2025 Sep · PMID 41143618 · Publisher ↗

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Clinical Analysis of Two Cases of Histiocytic Necrotizing Lymphadenitis Complicated with Macrophage Activation Syndrome.

Jin J, Lu S, Lin H

Iran J Allergy Asthma Immunol · 2025 Sep · PMID 41143617 · Publisher ↗

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Elucidating the Molecular Pathways of Long Noncoding RNA C6orf223 in Colorectal Cancer via microRNA Interactions and Transcriptomic Profiling.

Tutunchi S, Javanmard AR, Panahi G … +3 more , M Soltani B, Akbari A, Ghaderian SMH

Iran J Allergy Asthma Immunol · 2025 Sep · PMID 41143616 · Publisher ↗

Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with high-risk cases showing increased aggressiveness and poor prognosis. Recent studies suggest that long noncoding RNAs (lncRNAs) such as C6orf223... Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with high-risk cases showing increased aggressiveness and poor prognosis. Recent studies suggest that long noncoding RNAs (lncRNAs) such as C6orf223 may play crucial roles in CRC progression. This study investigated the expression and regulatory role of C6orf223 in high-risk versus low-risk CRC patients, focusing on its potential as a biomarker for diagnosis and prognosis. We conducted differential expression analysis using RNA-seq data to identify key genes in high-risk CRC, followed by correlation and pathway enrichment analyses to understand C6orf223. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves assessed the prognostic and diagnostic potential of C6orf223. RNA methylation and mutation patterns were analyzed to explore post-transcriptional regulation and genetic alterations in high-risk CRC. C6orf223 was significantly upregulated in high-risk CRC. High C6orf223 expression was associated with poor overall survival, and a biomarker panel that includes C6orf223 and microRNAs showed strong potential for accurate diagnosis. Methylation and mutation analyses revealed potential mechanisms enhancing C6orf223's stability and oncogenic activity. Our findings indicate that C6orf223 acts as a binder to and inhibits tumor-suppressive microRNAs, reducing their availability to regulate cancer-promoting genes and may serve as a valuable biomarker for CRC diagnosis and prognosis. Further research on lncRNA-microRNA interactions could provide insights for novel CRC therapies.

Exploring Inflammatory-related Hub Genes as Therapeutic Targets in Major Depressive Disorder: Implications for Immunological Pathways.

Wang R, Fan H, Feng Y … +2 more , Li H, Cui J

Iran J Allergy Asthma Immunol · 2025 Sep · PMID 41143615 · Publisher ↗

This study explored the mechanisms of action of inflammation related central genes in severe depression (MDD) and analyzes their potential as therapeutic targets. By identifying key genes and establishing the link betwee... This study explored the mechanisms of action of inflammation related central genes in severe depression (MDD) and analyzes their potential as therapeutic targets. By identifying key genes and establishing the link between immune regulatory mechanisms and depression, we provide a theoretical basis for developing more accurate diagnostic and treatment methods. Gene expression datasets related to MDD were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) associated with inflammatory processes were identified and analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Protein-protein interaction (PPI) networks were constructed to identify hub genes. Additionally, we explored regulatory networks of miRNAs, transcription factors, and potential drug interactions were explored. Immune infiltration analysis was performed to examine immune cell profiles. Seven key genes-HMGB1, HSP90AB1, MAPK1, MMP9, MYD88, S100A12, and TLR2-were identified as central players in the inflammatory pathways underlying MDD. These genes demonstrated moderate diagnostic accuracy with AUC values ranging from 0.5 to 0.7. Enrichment analyses revealed significant associations with immune signaling pathways, including IL-17 and Toll-like receptor signaling. Immune infiltration analysis highlighted altered abundances of regulatory T cells, neutrophils, and dendritic cells in MDD samples. Inflammatory-related hub genes play crucial roles in linking immune dysregulation to the pathophysiology MDD pathophysiology. These findings offer insights into the immunological underpinnings of MDD and present potential therapeutic targets for intervention through immune-modulatory approaches.

The Role of LINC02381 in Modulating Cisplatin Resistance in Ovarian Cancer: A Bioinformatics Approach.

Karbalaei Pazoki Z, Soltani BM, Hosseini M … +1 more , Irani S

Iran J Allergy Asthma Immunol · 2025 Sep · PMID 41143614 · Publisher ↗

Cisplatin resistance presents a significant challenge in cancer therapy, emphasizing the necessity for identifying new regulatory elements that influence drug response. Recent research has revealed the importance of long... Cisplatin resistance presents a significant challenge in cancer therapy, emphasizing the necessity for identifying new regulatory elements that influence drug response. Recent research has revealed the importance of long noncoding RNAs (lncRNAs) in chemotherapy resistance, with LINC02381 identified as a potential regulatory factor. Through an in-depth bioinformatics analysis, we investigated the impact of LINC02381 on cisplatin resistance in ovarian cancer across various datasets. By conducting differential expression analysis, survival analysis, gene set enrichment analysis (GSEA), and constructing protein-protein interaction (PPI) networks, we identified key pathways associated with LINC02381 expression. The results indicated that the altered expression of LINC02381 in patients treated with cisplatin was associated with reduced survival. Functional studies and correlation analyses further demonstrated that this LncRNA influences critical pathways and genes related to apoptosis, efflux, DNA repair, and EMT. Lastly, through an examination of its interactions with microRNA and protein networks, we identified LINC02381 as a ceRNA implicated in cisplatin resistance. Our findings suggest that LINC02381 may influence cisplatin sensitivity in ovarian cancer and establish a basis for further experimental validation, including molecular assays or in vivo analyses, and suggest the potential therapeutic targeting of LINC02381 to combat chemoresistance.

Exploring the Therapeutic Potential of Fluorinated CXCR4 Inhibitor A1: Insights from Breast Cancer In Vitro Investigations.

Rahimi A, Khorramdelazad H, Darehkordi A … +5 more , Hassanshahi G, Khoshmirsafa M, Karimi M, Falak R, Safari E

Iran J Allergy Asthma Immunol · 2025 Sep · PMID 41143613 · Publisher ↗

The impacts of the CXC motif chemokine 12 (CXCL12)/ C-X-C chemokine receptor type 4 (CXCR4) axis on the infiltration of anti-tumor and pro-tumor immune cells in the tumor microenvironment (TME) of breast cancer (BCa) hav... The impacts of the CXC motif chemokine 12 (CXCL12)/ C-X-C chemokine receptor type 4 (CXCR4) axis on the infiltration of anti-tumor and pro-tumor immune cells in the tumor microenvironment (TME) of breast cancer (BCa) have been noted in previous studies. Accordingly, regulating the downstream signals of this axis can effectively increase CD8+ cytotoxic T cells and decrease the frequency of immunosuppressive cells in the TME. This study investigated the anti-tumor effects of N, N''-thiocarbonylbis (N'-(3,4-dimethylphenyl)-2,2,2 trifluoroacetimidamide) (A1), a novel fluorinated CXCR4 inhibitor on a BCa cell line. In this study, the impacts of A1 on cell viability, proliferation, apoptosis, and cell cycle were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays. Moreover, the effect of A1 on the number of CXCR4+ 4T1 cells was measured by flow cytometry. A1 treatment exhibited cytotoxic effects on 4T1 cells, promoting cell apoptosis and G2/M cell cycle arrest. In addition, A1-treated cells showed a reduced cell proliferation than CXCL12 treated cells. Furthermore, treatment with A1 alongside CXCL12 significantly decreased the number of CXCR4+ cells compared to the control group treated with only CXCL12 as a proliferator factor. These results indicate that A1 exerts potential anti-tumor effects and may serve as a possible therapeutic agent for BCa treatment; however, further studies are required.

Association between HLA-DRB1.2 Genotypic Diversity and Cervical Cancer in Women Infected with the Human Papillomavirus.

Sedaghat S, Nikbakht Brujeni G, Shamsian SAA … +1 more , Sohrabi Haghdoost N

Iran J Allergy Asthma Immunol · 2025 Sep · PMID 41143612 · Publisher ↗

Cervical cancer is a significant public health concern, particularly in women infected with the human papillomavirus (HPV). Recent evidence suggests that host genetic factors, specifically those related to the human leuk... Cervical cancer is a significant public health concern, particularly in women infected with the human papillomavirus (HPV). Recent evidence suggests that host genetic factors, specifically those related to the human leukocyte antigen (HLA) system, may also play a crucial role in determining susceptibility to cervical cancer in HPV-infected individuals. In this study, 86 patients with HPV and 27 healthy donors were selected from May 2023 to February 2024. HLA-DRB1 genotypes were determined using polymerase chain reaction followed by high-resolution melting curve analysis (HRM). Genotype frequencies in patients were compared with those in the control group from donors. Based on the HRM analysis, 10 genotypes were found in both patients and controls (profiles A-J). In the analysis of HLA-DRB1 genotypes, C, F, and I showed significant associations with HPV infection, indicating a possible protective effect against infection. Notably, genotype B was strongly linked to high-risk HPV, while genotype A was associated with low-risk HPV and is relevant to infection history. However, the remaining genotypes examined in the study did not exhibit significant associations with the analyzed parameters. This study contributes valuable evidence regarding the role of HLA-DRB1 genotypes in cervical cancer susceptibility and highlights the potential clinical implications for risk assessment and targeted immunotherapies. The use of HRM for HLA typing offers advantages that are efficient, accurate, and scalable, making it suitable for large-scale studies and clinical applications.

The Relationship between Thioredoxin-2, Systemic Immune-inflammatory Index, and Short-term Adverse Cardiovascular Events in Septic Cardiomyopathy.

Zhang Y, Han D, Yang C … +4 more , Chao Y, Xiao Q, Sun C, Guo Y

Iran J Allergy Asthma Immunol · 2025 Sep · PMID 41143611 · Publisher ↗

To explore the relationship between thioredoxins (Trx) -2, systemic-immune inflammatory index (SII), and short-term major adverse cardiac events (MACE) in septic cardiomyopathy (SCM). A retrospective study was conducted... To explore the relationship between thioredoxins (Trx) -2, systemic-immune inflammatory index (SII), and short-term major adverse cardiac events (MACE) in septic cardiomyopathy (SCM). A retrospective study was conducted on 98 SCM patients admitted to Affiliated Jinling Hospital, Medical School of Nanjing University Emergency Intensive Care Unit (EICU) from July 2022 to June 2024. Patients underwent routine blood tests and data assessment upon admission. Based on the occurrence of MACE by day 28, patients were divided into the MACE group and the non-MACE (N-MACE) group. Clinical data were collected, and logistic regression, along with restricted cubic spline models, analyzed the relationships between SII, Trx-2, and MACE risk in SCM patients. Among the 98 SCM patients included, there were 35 (35.71%) in the MACE group and 63 (64.29%) in the N-MACE group. Logistic regression analysis showed that elevated SII and serum Trx-2 levels correlated with an increased risk of MACE within 28 days post-admission for SCM patients. Restricted cubic spline analysis revealed a linear dose-response relationship between both SII and Trx-2 levels with short-term MACE risk in SCM. The ROC curve showed AUC values of 0.869 for LVEF, 0.881 for SII, while combining SII + Trx-2 yielded 0.926 (95% CI: 0.862-0.989), with specificity at 83.98 % and sensitivity at 98.80%. The abnormal increase of serum SII and Trx-2 levels in SCM patients is related to the occurrence of MACE within 28 days after admission. The risk of MACE increases with the increase of serum SII and Trx-2 levels.

Analysis of the Relationship between Pan-immune-inflammation Value and the Clinical Pathological Characteristics and Surgical Prognosis of Thyroid Cancer.

Liang W, Fu D

Iran J Allergy Asthma Immunol · 2025 Sep · PMID 41143610 · Publisher ↗

This study aimed to explore the relationship between the preoperative pan-immune-inflammation value (PIV) and the clinicopathological characteristics and surgical prognosis of thyroid cancer. This retrospective cohort st... This study aimed to explore the relationship between the preoperative pan-immune-inflammation value (PIV) and the clinicopathological characteristics and surgical prognosis of thyroid cancer. This retrospective cohort study included 165 patients with thyroid cancer who underwent surgery. The value and clinical applicability of PIV and other immune-inflammatory biomarkers in assessing disease-free survival (DFS) were compared based on the area under the receiver operating characteristic (ROC) curve (AUC) and decision curve analysis (DCA). Patients were divided into high and low PIV groups according to the optimal cutoff value to assess the correlation between PIV and pathological characteristics. The Kaplan-Meier method was used for DFS analysis, and a Cox proportional hazards model was used to analyze the factors affecting DFS. The AUC of PIV for predicting DFS was higher than that of other immune-inflammatory biomarkers, and PIV demonstrated the highest clinical utility. Compared with the low PIV group, the high PIV group had a lower proportion of papillary thyroid carcinoma, a higher proportion of anaplastic thyroid carcinoma, and higher rates of stage III-IV disease, lymph node metastasis, maximum tumor diameter ≥2 cm, and multiple lesions. The DFS was significantly shorter in the high PIV group than in the low PIV group. After adjusting for confounding factors, a high PIV level was an independent risk factor for poor surgical outcomes. In conclusion, preoperative PIV is associated with the pathological type of thyroid cancer, TNM stage, lymph node metastasis status, and maximum tumor diameter. Furthermore, a high PIV level can increase the risk of poor surgical outcomes.
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