Original Article
Jun Zhang; Yang Zhang; Jinwei Zhang
Abstract
Background: Cervical cancer progression is driven by immune evasion mechanisms, including PD-L1-mediated suppression of T cell activity. BATF, a transcription factor, has been linked to tumor immunity; cancer remains incompletely understood.Objective: This study investigates the BATF-STAT1-PD-L1 axis ...
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Background: Cervical cancer progression is driven by immune evasion mechanisms, including PD-L1-mediated suppression of T cell activity. BATF, a transcription factor, has been linked to tumor immunity; cancer remains incompletely understood.Objective: This study investigates the BATF-STAT1-PD-L1 axis in tumor progression and immune regulation.Methods: BATF expression was analyzed in cervical cancer tissues and cell lines. Functional assays assessed the impact of BATF knockdown on proliferation, apoptosis, autophagy, and migration. STAT1 regulation was examined via chromatin immunoprecipitation and Western blot. PD-L1 expression was measured by flow cytometry. In vivo xenograft models were used to evaluate tumor growth and response to PD-L1 blockade.Results: BATF was upregulated in cervical cancer and promoted tumor growth, metastasis, and immune evasion. BATF knockdown suppressed proliferation, enhanced apoptosis and autophagy, and reduced migration. Mechanistically, BATF transcriptionally activated STAT1, which induced PD-L1 expression. BATF suppression enhanced CD8⁺ T cell infiltration and improved the efficacy of PD-L1 blockade in vivo.Conclusion: BATF promotes cervical cancer progression by modulating STAT1 and PD-L1. Targeting BATF may enhance anti-tumor immunity and improve immunotherapy outcomes.
Original Article
Marziyeh Mousazadeh; Maryam Nikkhah; Negar Seyed; Sima Rafati; Saman Hosseinkhani
Abstract
Background: Dendritic cells (DCs) are the most potent antigen-presenting cells, playing a central role in T cell activation and the stimulation of B cell antibody production. Owing to their immunological significance, DCs have been extensively explored for applications in cancer immunotherapy, ...
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Background: Dendritic cells (DCs) are the most potent antigen-presenting cells, playing a central role in T cell activation and the stimulation of B cell antibody production. Owing to their immunological significance, DCs have been extensively explored for applications in cancer immunotherapy, dendritic cell–based vaccines, and strategies to overcome the immunosuppressive tumor microenvironment.Objective: Given the broad applications of DCs and the need for efficient generation protocols, the present study aimed to optimize key parameters influencing the production of bone marrow-derived dendritic cells (BMDCs).Methods: Variables such as mouse strain, cytokine concentrations, culture plate type, differentiation duration, incubation temperature, cell seeding density, and media replacement intervals were evaluated. CD11c expression was used as the primary marker to quantify BMDCs, while CD80 and CD86 were used as indicators of maturation status.Results: The optimized protocol yielded 60-70% CD11c+ BMDCs and 70-80% CD80/CD86 expression within 5 days.Conclusion: This robust and highly reproducible protocol offers valuable applications for in vitro dendritic cell generation studies.
Original Article
Ghanyia Jasim Shanyoor; Mukhtar Khamis Haba; Ban Hadi Hameed
Abstract
Background: Miscarriage occurs when a pregnancy ends spontaneously before the fetus is viable outside the uterus. Early miscarriage, sometimes referred to as first-trimester miscarriage, happens before 12 weeks. Vascular endothelial growth factor (VEGF), an angiogenic protein essential for blood vessel ...
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Background: Miscarriage occurs when a pregnancy ends spontaneously before the fetus is viable outside the uterus. Early miscarriage, sometimes referred to as first-trimester miscarriage, happens before 12 weeks. Vascular endothelial growth factor (VEGF), an angiogenic protein essential for blood vessel formation, and cluster of differentiation 68 (CD68), a marker of macrophages, are vital to the immune response.Objective: This research aimed to evaluate VEGF and CD68 expression patterns in placental tissues and decidua from first-trimester miscarriage, to ascertain their potential roles in immune response and angiogenesis in miscarriage.Methods: The study included 60 women who experienced spontaneous abortion during the first trimester, 30 with missed abortion, and 30 with incomplete abortion. Using immunohistochemical staining, the expression of CD68 and VEGF in decidua and placental tissues was investigated. Expression levels were scored semi-quantitatively by averaging data from five fields per slide and subjected to statistical analysis.Results: Building on these methods, immunohistochemical staining confirmed significantly elevated CD68 expression in both placental and decidua tissues from missed and incomplete abortions, indicating enhanced macrophage infiltration. Widespread staining (>50%) was seen in 50% of incomplete abortion decidua and 30% of missed abortion tissues. In contrast, VEGF expression was predominantly negative across all samples, with no case showing positive staining, indicating impaired angiogenesis.Conclusion: The findings highlight a dual pathological mechanism in early miscarriage characterized by enhanced inflammatory macrophage infiltration and deficient angiogenic support. This imbalance may contribute to placental dysfunction and pregnancy failure. These results underscore the potential diagnostic and therapeutic relevance of immune–angiogenic pathways in early miscarriage
Original Article
Lida Aslanian-Kalkhoran; Mohammad Sadegh Soltani-Zangbar; Ali Aghebati-Maleki; Mahya AhmadpourYoushanlui; Mehdi Yousefi; Leili Aghebati Maleki
Abstract
Background: Autophagy genes are essential for proper uterine function, reproductive physiology, and the maintenance of endometrial atrophy (EA).
Objective: This study aims to clarify how these genes impact endometrial thickness and their significance in the apoptosis of peripheral blood mononuclear ...
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Background: Autophagy genes are essential for proper uterine function, reproductive physiology, and the maintenance of endometrial atrophy (EA).
Objective: This study aims to clarify how these genes impact endometrial thickness and their significance in the apoptosis of peripheral blood mononuclear cells (PBMCs) from patients with thin endometria.
Methods: Blood samples were collected from 40 patients with a thin endometrium and 40 healthy controls, all in the non-pregnancy stage. Real-Time PCR was used to measure the expression levels of autophagy genes ATG5, ATG7, LC3B, Beclin1, FOXO1, FOXO3a, FOXO4, and FOXO6 in 40 women with thin endometrium and 40 healthy women. Apoptosis was also assessed by flow cytometry. To further elucidate the biological pathways and processes associated with the differentially expressed autophagy genes, we conducted a KEGG pathway enrichment analysis using the EnrichR tool.
Results: Evaluation of autophagy gene expression showed a significant difference between the studied groups, with higher expression of ATG5, ATG7, LC3B, Beclin1, FOXO1, FOXO3a, FOXO4, and FOXO6 in the patient group. Moreover, there was a positive correlation between LC3B expression and the frequency of apoptotic cells in the studied patients. The EnrichR tool identified the enriched pathways: "Shigellosis," "FOXO signaling," "Fruptosis," and, to a lesser extent, "Longevity regulating pathway," "Autophagy," and "Mitophagy."
Conclusion: Our results showed that autophagy genes associated with apoptosis in PBMCs may be involved in endometrial thinning in EA patients.
Original Article
Muhammad Bar Khan; Sanaullah Khan; Muhammad Fawad Khan; Khair Rafiq; Muhammad Yaqoob; Muhammad Adnan
Abstract
Background: Recurrent pregnancy loss (RPL) is a global health challenge in women. It has been reported that Toxoplasma gondii (T. gondii) infection and interleukin-6 (IL-6) bioavailability contribute to RPL.
Objective: This study investigated IL-6 and IL-6 receptor (IL-6R) gene polymorphisms and blood ...
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Background: Recurrent pregnancy loss (RPL) is a global health challenge in women. It has been reported that Toxoplasma gondii (T. gondii) infection and interleukin-6 (IL-6) bioavailability contribute to RPL.
Objective: This study investigated IL-6 and IL-6 receptor (IL-6R) gene polymorphisms and blood IL-6 levels in T. gondii-infected women with RPL.
Methods: The study comprised 163 women, including 83 infected (Group A: subgroups A1, A2) and 80 healthy (Group B). Demographic data, blood, and placental tissue samples were collected. The blood samples were screened for IL-6 levels through ELISA. DNA was extracted, and T. gondii-DNA was identified using PCR. IL-6 and IL-6R genes were amplified by PCR and sequenced using the Sanger method.
Results: The IL-6 gene -174G/C (p=0.005) and -597G/A (p=0.0012) polymorphisms were significantly associated, while the -572G/C polymorphism was insignificantly associated (p=0.143) with infection and RPL. The mean blood IL-6 level was significantly variable across all groups (p < 0.001). The IL-6 gene -174GG and -597GG genotypes, and the IL-6R gene AA genotype, were common in Group-A2 (47.5%, 37.5%, 50%) and Group-B (56.2%, 60%, 68.8%), respectively, and were also significantly associated with elevated blood IL-6 levels. The -572GG genotype was common and was not significantly associated with elevated blood IL-6 levels across all groups (p=0.143). The IL-6 gene -174CC and -597AA genotypes and IL-6R gene CC genotype were highly prevalent in Group-A1 (48.8%, 41.9%, and 51.1%, respectively) and associated with low blood IL-6 levels.
Conclusion: The IL-6 gene -174G/C, -597G/A, and IL-6R gene A/C polymorphisms play significant roles in RPL in women infected with T. gondii, and change IL-6 bioavailability.
Original Article
Mahsa Rostami; Mansour Moazenzadeh; Abdollah Jafarzadeh; Ahmad Shakeri; Parya Jangipour Afshar; Nazanin Zeinali; Hamidreza Rashidinejad
Abstract
Background: Atherosclerosis is a chronic inflammatory, immune-mediated disease that is a leading cause of global mortality and disability. Coronary artery calcification (CAC) is a key predictor of the severity of coronary artery disease (CAD). Interleukin-38 (IL-38), a newly identified anti-inflammatory ...
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Background: Atherosclerosis is a chronic inflammatory, immune-mediated disease that is a leading cause of global mortality and disability. Coronary artery calcification (CAC) is a key predictor of the severity of coronary artery disease (CAD). Interleukin-38 (IL-38), a newly identified anti-inflammatory cytokine, may modulate inflammation and prevent atherosclerosis progression.Objective: This study aimed to evaluate the association between serum IL-38 levels and CAC severity among patients referred to the CT angiography unit at Razieh Firooz Hospital in Kerman City.Methods: In this cross-sectional study, 151 patients aged 50–70 years were evaluated. The mean age of the participants was 60.1 ± 6.9 years. CAC severity was determined using the Agatston scoring method and multi-detector CT scanners. Serum IL-38 levels were measured via enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using an independent T-test and multivariable logistic regression.Results: Comparing serum IL-38 levels across CAC severity categories showed a statistically significant difference (P = 0.039). Mean serum IL-38 in patients with non-severe and severe calcification were 16.8 ± 5.5 pg/mL and 19.4 ± 4.9 pg/mL, respectively. However, in the multivariable regression analysis, adjusted for major risk factors including sex, age, diabetes, hypertension, and smoking, the association between serum IL-38 levels and CAC severity was not significant (P>0.05). In subgroup analyses, the significant association between IL-38 and CAC severity was observed only in older participants and in patients with established cardiovascular risk factors.Conclusion: Although serum IL-38 levels were higher in patients with severe CAC, this association did not remain significant after adjustment for major cardiovascular risk factors. Therefore, the observed elevation may reflect age- or risk-related inflammatory changes rather than a direct role of IL-38 in calcification. So, this relationship remains unclear. Further investigation is needed to clarify the potential context-dependent function of IL-38 in atherosclerosis progression.
Original Article
Ismail Tuncekin; Murat Toprak
Abstract
Background: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic autoimmune inflammatory disorders in which TNF-α plays a key role. Anti-TNF agents are widely used in the management of these diseases.
Objective: Since TNF-α is also involved in the pathogenesis of autoimmune ...
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Background: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic autoimmune inflammatory disorders in which TNF-α plays a key role. Anti-TNF agents are widely used in the management of these diseases.
Objective: Since TNF-α is also involved in the pathogenesis of autoimmune thyroid disease (AITD), this study aimed to assess whether anti-TNF therapy influences thyroid function.
Methods: This prospective study included 50 RA and 51 AS patients aged 18–85 years. Patients received either conventional treatment (DMARDs and NSAIDs/sulfasalazine) or anti-TNF agents. Serum TSH, free T4, and anti-TPO levels were measured at baseline and after 6 months. Thyroid dysfunction and AITD prevalence were compared between the two treatment groups.
Results: In the RA group, subclinical hyperthyroidism was observed in both arms; in the anti-TNF group, one patient had hypothyroidism, and another had subclinical hypothyroidism. Improvement in subclinical hyperthyroidism was observed in one patient in the DMARD arm, in one patient with hypothyroidism, and in one patient with subclinical hyperthyroidism in the anti-TNF arm (p>0.05). In the AS group, central hyperthyroidism developed in one patient receiving conventional treatment. In the anti-TNF group, one patient with subclinical hypothyroidism improved to normal values, while another developed central hypothyroidism. Anti-TPO positivity was 18% in the conventional group and 3.4% in the anti-TNF group (p>0.05). A significant TSH change was observed only in the RA-DMARD group (p < 0.05), while no significant changes in free T4 were detected in any group.
Conclusion: Anti-TNF therapy showed no significant effect on thyroid function or autoimmune thyroid disease in patients with RA and AS during a six-month follow-up.
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