The Potential Influence of Immune Modulatory Molecules (TGF-βIII and CTLA-4) in Pathogenicity of PCOS

المجلة: Karbala International Journal of Modern Science

سنة النشر: 2024

تاريخ النشر: 2024-07-01

Polycystic ovary syndrome (PCOS) is characterised by chronic anovulation, hyperandrogenism, polycystic ovaries, and immunological dysregulation. Immune homeostasis and inflammation management require immune functions. T-regulatory cells (Tregs) regulate PCOS's immune system, inflammation, insulin resistance, ovarian function, and homeostasis. Transforming growth factor βIII (TGF-βIII) and Cytotoxic-T- lymphocyte-associated-protein-4 (CTLA-4) receptors on the surfaces of Treg cells are important for controlling the immune system. The study included 68 PCOS patients and 22 non-PCOS women controls aged 20–45. The waist-hip ratio (WHR) determines obesity. We evaluated serum levels and gene expression of TGF-βIII and CTLA-4 via ELISA and real-time PCR. Women with PCOS had significantly higher TGF-βIII and CTLA-4 levels compared to controls. The study reveals a considerable increase in TGF-βIII and CTLA-4 gene expression in PCOS patients compared to the control. Compared to controls, PCOS aged < and > 25 had higher serum TGF-III and CTLA-4 concentrations. According to the RT-PCR test, the PCOS (> 25) had much higher amounts of TGF-βIII and CTLA-4 gene expression than the control. TGF- βIII and CTLA-4 also increased at < and > 0.8 of WHR compared to the control. The RT-PCR results showed that the obese PCOS had much higher levels of TGF-βIII and CTLA-4 gene expression (>0.8) than the control. Based on clinical signs, serum TGF-βIII levels and folding were significantly higher in women with PCOS who had irregular periods compared to women whose cycles were normal. These data indicate a role for TGF-βIII and CTLA-4 in PCOS etiology. This study suggests targeting TGF-βIII and CTLA-4 for PCOS immunotherapy.

Bone Morphogenetic Protein (BMP)9 in cancer development: Mechanistic, Diagnostic, and Therapeutic Approaches?

المجلة: Journal of Drug Targeting

سنة النشر: 2023

تاريخ النشر: 2023-06-01

Bone morphogenetic protein (BMP)-9 is considered a member of the transforming growth factor (TGF)β superfamily. It was first found as an inducer of bone and cartilage formation and then discovered that this factor mediates several physiologic functions and hemostasis. Besides physiological conditions, BMP9 has also been elucidated that it is involved in several pathological situations, especially cancer. In various cancers, dysregulation of BMP9 has raised the issue that BMP9 might play a conflicting role in tumor development. BMP9 binding to its receptors (BMPRs), including ALKs and BMPRII, induces canonical SMAD-dependent and non-canonical PI3K/AKT and MAPK signaling pathways in tumor cells. BMP9, via inducing apoptosis, inhibiting tumor-promoting cell signaling pathways, suppressing epithelial-mesenchymal transition (EMT) process, blocking angiogenesis, and preventing cross-talk in the tumor microenvironment, mainly exerts tumor-suppressive functions. In contrast, BMP9 triggers tumor-supportive signaling pathways, promotes EMT, and enhances angiogenesis, suggesting that BMP9 is also involved in tumor development. It has been demonstrated that modulating BMP9 expression and functions might be a promising approach to cancer treatment. It has also been indicated that evaluating BMP9 expression in cancers might be a biomarker for predicting cancer prognosis. Overall, BMP9 would provide a promising target in cancer management.

Clonality assay of IGH gene rearrangement in Iraqi patients with non hodgkin's lymphoma using FFPE tissue

المجلة: Journal of Pharmaceutical Sciences and Research

سنة النشر: 2019

تاريخ النشر: 2019-10-12

Background: B cell Non Hodgkin lymphoma is a malignant that arose in B lymphocytes and dividing into several subtypes. A role of B-cell receptor (BCR) in lymphomagenesis has been inferred by studying immunoglobulin genes in human lymphoma. During maturation of b cell Ig gene undergoing to the process rearrangement. Ig gene rearrangement in B-cell lymphomas arise from monoclonal enlarged B-cells, this may be used as markers of neoplasm clonality. Material and methods: Collected fifty six of FFPE tissue, 37 of NHL and 19 of reactive lymphoid hyperplasia that use as control for polyclonality, were collected from Baghdad medical city and used as source of DNA and the clonality of B-cell lymphoma determined by polymerase chain reaction (PCR) and heteroduplex analysis to separated monoclonal from polyclonal according to BIOMED-2 protocol used as diagnostic tool of B-NHL Results: The positive clonality was detected in rate 70% (26/37) as monoclonal while 29% (11/37) the clonality showed a polyclonal pattern. in group with DLBCL clonality was observed in 66%(10/15) as monoclonal, in SLL monoclonality detected in 75%(3/4), in BL monoclonality showed in 66%(2/3), in MALT monoclonality showed in 50%(1/2) and in patients diagnosed with FL and NMZL 100% of case showed a monoclonal pattern. In reactive lymphoid hyperplasia 100%(19/19) the clonality showed a polyclonal pattern. Conclusion: Use the complete IGH rearrangement to determination the clonality of B cell has provided a good tool for diagnostic the B cell lymphoma.