Associations of ANGPT2 expression and its variants (rs1868554 and rs7825407) with multiple myeloma risk and outcomePopek-Marciniec, Styk, Chocholska
et alFront Oncol (2025) 15, 1468373
Abstract: The growth of blood vessels from the existing vasculature has a significant impact on the course of multiple myeloma (MM). The ANGPT2 (angiopoietin-2) protein is encoded by the ANGPT2 gene and plays an important role in angiogenesis. The expression of proangiogenic proteins is influenced not only by microenvironmental factors but also by genetic changes. We analyzed two variants/polymorphisms of the ANGPT2 gene, rs1868554 (T>A) and rs7825407 (G>C). Both are located in the intron sequence and can affect the final mRNA sequence by modifying splicing.Therefore, we assessed the impact of selected variants on ANGPT2 gene expression at the mRNA and protein levels. Additionally, we evaluated the associations of the analyzed genetic changes with the clinical and laboratory parameters of the disease and the response to bortezomib/thalidomide-based therapies. We hypothesize that variants and expression of the ANGPT2 gene may be associated with a greater risk of MM development and may also affect the response to treatment in MM patients.Genomic DNA extracted from 103 newly diagnosed MM patients and 120 healthy blood donors was used to analyze ANGPT2 variants (via automated DNA sequencing). RNA was subjected to real-time PCR to determine ANGPT2 expression at the mRNA level. The concentration of angiopoietin-2 (in MM sera) was determined by ELISA.The results of our study showed that individuals with the AA genotype of rs1868554 and the CC genotype of rs7825407 had a greater risk of developing MM (OR=6.12, p=0.02 and OR=6.01, p=0.02, respectively). The ANGPT2 gene variants did not affect ANGPT2 expression at the mRNA level. However, ANGPT2 expression was positively correlated with CRP (Spearman's rho 0.26, p<0.05) and negatively correlated with LDH (Spearman's rho -0.25, p<0.05) in MM patients.Our results showed that ANGPT2 expression at the mRNA level correlates with CRP, a negative prognostic factor in MM. The ANGPT2 protein is a proangiogenic factor, and its concentration is significantly greater in MM patients than in healthy individuals, which was also confirmed in our research. Therefore, this protein with VEGF and HB-EGF, should be considered in the future as a markers of angiogenesis in MM.Copyright © 2025 Popek-Marciniec, Styk, Chocholska, Szudy-Szczyrek, Sidor, Swiderska-Kolacz, Hus, Czerwik-Marcinkowska and Zmorzynski.
Pd Icosahedral Nanoparticles Promote Skin Wound Healing by Enhancing SP1-HBEGF Axis-Mediated Keratinocytes ProliferationHe, Li, Zhao
et alInt J Nanomedicine (2025) 20, 3067-3081
Abstract: Impaired wound healing leads to compromised cutaneous barrier and dysfunction, which still remains a challenging problem. However, safe and efficient materials and treatments for promoting wound healing are still lacking. Metal nanoparticles especially palladium nanoparticles (Pd NPs) have attracted tremendous interests in medical application in recent years, due to its unique physicochemical properties and biological inertness. Thereinto, Pd icosahedra nanoparticles (Pd Icos NPs) and Pd octahedra nanoparticles (Pd Oct NPs) have superior catalytic activity compared to other shapes but the application in skin wound healing have not been studied and reported.Pd Oct NPs and Pd Icos NPs were synthesized by seed-mediated growth method and one-step synthesis method and characterized by series physical chemical assays. The acute full-thickness skin excision wound mouse model was used to access the wound healing potential and screen out the effective materials-Pd Icos NPs. Next evaluate the biotoxicity and safety of Pd Icos NPs and both in HaCaT cells and in vivo. Further examine related molecules expression by RT-qPCR and WB in HaCaT cells and wound tissues with Pd Icos treatment. Then knockout the related molecules both in HaCaT cells and in vivo to validate the molecular mechanism of these molecules in the phenotype of wound healing promoted by Pd Icos NPs.Pd Icos NPs with surface and tensile strain rather than Pd Oct NPs can promote skin wound healing. Pd Icos NPs upregulates the expression of HBEGF by promoting the production of transcription factor SP1, and contributes to keratinocytes proliferation and accelerating acute full-thickness skin wound healing.Pd Icos NPs represent an effective and safe material for skin wound healing, suggesting a potential novel therapeutic strategy.© 2025 He et al.
The impact of ERN1 endoribonuclease activity inhibition on TOB1, HBEGF, and TWIST1 genes expression in U87MG glioblastoma cellsMinchenko, Sliusar, Viletska
et alEndocr Regul (2025) 59 (1), 24-32
Abstract: Objective. It is known that inhibition of the endoplasmic reticulum transmembrane signaling protein (ERN1) suppresses the glioblastoma cells proliferation. The present study aims to investigate the impact of inhibition of ERN1 endoribonuclease and protein kinase activities on the TOB1, HBEGF, and TWIST1 gene expression in U87MG glioblastoma cells with an intent to reveal the role of ERN1 signaling in the regulation of expression of these genes. Methods. The U87MG glioblastoma cells with inhibited ERN1 endoribonuclease (dnrERN1) or both enzymatic activities of ERN1 (endoribonuclease and protein kinase; dnERN1) were used. Cells transfected with empty vector served as controls. Wild-type glioblastoma cells were used for mRNA silencing. The expression level of the TOB1, HBEGF, and TWIST1 genes and microRNA were studied by quantitative RT-PCR. Results. We found that inhibition of ERN1 endoribonuclease activity led to a strong down-regulation of HBEGF gene expression in glioblastoma cells and did not significantly change the expression of TOB1 and TWIST1 genes. At the same time, inhibition of both enzymatic activities of ERN1 strongly increased the expression of the TOB1 gene and down-regulated HBEGF and TWIST1 genes in glioblastoma cells. The expression of TWIST1 gene increased, but HBEGF and TOB1 genes significantly decreased in cells with silencing of ERN1 mRNA by specific siRNA. At the same time, silencing of XBP1 mRNA reduced the expression of HBEGF gene only. In addition, in glioblastoma cells with ERN1 knockdown, the level of miR-96-5p was suppressed, but miR-182-5p was increased and could promote post-transcriptional expression of TWIST1, HBEGF, and TOB1 mRNAs. Conclusion. The results of the present study demonstrate that inhibition of ERN1 strongly up-regulated the expression of the anti-proliferative TWIST1 gene through protein kinase activity of ERN1 and that decreased HBEGF and TOB1 genes expression was also controlled preferentially by ERN1 protein kinase activity. These changes in the expression level of TWIST1, HBEGF, and TOB1 genes may also contribute to ERN1 knockdown-mediated suppression of glioblastoma cells proliferation.© 2025 Oleksandr H. Minchenko et al., published by Sciendo.
Universal First-Trimester Screening Biomarkers for Diagnosis of Preeclampsia and Placenta Accreta SpectrumTimofeeva, Fedorov, Tarasova
et alBiomolecules (2025) 15 (2)
Abstract: Disruptions in epigenetic mechanisms regulating placentation, particularly imbalances in the levels of small non-coding RNAs, contribute to various pregnancy complications, including preeclampsia (PE) and placenta accreta spectrum (PAS). Given that abnormal trophoblast differentiation, invasiveness, and angiogenesis-reduced in PE and excessive in PAS-are central to the pathogenesis of these conditions, this study aimed to identify universal circulating piRNAs and their targets.Small RNA deep sequencing, quantitative reverse transcription combined with real-time polymerase chain reaction, magnetic bead-based multiplex immunoassay, ELISA, and Western blotting were employed to quantify circulating piRNAs and proteins in the blood serum of pregnant women during the 11th-14th weeks of gestation.Statistically significant negative correlations were identified between PE- and PAS-associated piRNAs (hsa_piR_019122, hsa_piR_020497, hsa_piR_019949, and piR_019675) and several molecules, including Endoglin, IL-18, VEGF-A, VEGF-C, Angiopoietin-2, sFASL, HB-EGF, TGFα, and Clusterin. These molecules are involved in processes such as angiogenesis, inflammation, the epithelial-mesenchymal transition, cell proliferation, adhesion, and apoptosis. A first-trimester pregnancy screening algorithm was developed using logistic regression models based on Clusterin concentration and the levels of hsa_piR_020497, hsa_piR_019949, piR_019675, and hsa_piR_019122.The proposed screening tool for early pregnancy monitoring may enable the prediction of PE or PAS in the first trimester, allowing timely interventions to reduce maternal and perinatal morbidity and mortality.
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