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Curr. Issues Mol. Biol., Volume 47, Issue 9 (September 2025) – 5 articles

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15 pages, 1676 KiB

Open AccessArticle

Mitigating Oxidative Stress and Anti-Angiogenic State in an In Vitro Model of Preeclampsia by HY-12, an Organofluorine Hydrazone Antioxidant

by Zsuzsanna K. Zsengellér, Maxim Mastyugin, Adrianna R. Fusco, Bernadett Vlocskó, Maximilian Costa, Coryn Ferguson, Diana Pintye, Réka Eszter Sziva, Saira Salahuddin, Brett C. Young, Marianna Török and Béla Török

Curr. Issues Mol. Biol. 2025, 47(9), 680; https://doi.org/10.3390/cimb47090680 (registering DOI) - 24 Aug 2025

Abstract

Preeclampsia (PE) is a hypertensive disorder impacting 5–7% of pregnancies globally. With no causative treatment available, diagnosed patients have limited therapeutic options, putting them at risk for pregnancy complications. The induction of oxidative stress by ROS—one of the major contributors in PE pathogenesis—causes downstream signaling and production of anti-angiogenic factors, such as sFLT1 and sEng. The anti-angiogenic factors may cause endothelial and trophoblast dysfunction, contributing to the development of hypertension, proteinuria, and in severe cases, eclampsia. To target placental oxidative stress, we developed and evaluated an organofluorine hydrazone antioxidant, HY-12, in vitro. Human trophoblast (HTR8/SVneo) cells were incubated with hydrogen peroxide to induce oxidative stress and act as a model of PE. The goal of the study was to assess the efficacy of HY-12 and its ability to reduce cell injury, mitochondrial stress, and anti-angiogenic response. In our human trophoblast-based assays, pre-treatment with HY-12 reduced mitochondrial-derived ROS production in cells exposed to hydrogen peroxide, proving its ability to alleviate the oxidative stress associated with the pathogenesis of PE. HY-12 reduced HIF1A expression and sFLT1 protein expression in H₂O₂-exposed HTR8 cells. Furthermore, HY-12 improved the activity of the mitochondrial electron chain enzyme cytochrome C oxidase (COX) in the hydrogen-peroxide-treated HTR8/SVneo cells, which is a promising attribute of the compound. In reducing placental trophoblast oxidative stress, HY-12 shows promise as a potential treatment of preeclampsia. In vivo studies are warranted to further determine the efficacy of this compound. Full article

(This article belongs to the Special Issue Advanced Molecular Research on Hypertensive Disorders of Pregnancy (HDPs))

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15 pages, 676 KiB

Open AccessArticle

Integrating Molecular Diagnostics into Cervical Cancer Screening: A Workflow Using FFPE Tissue Samples

by Serena Varesano, Giulia Ciccarese, Paola Parente, Michele Paudice, Katia Mazzocco, Simone Ferrero and Valerio Gaetano Vellone

Curr. Issues Mol. Biol. 2025, 47(9), 679; https://doi.org/10.3390/cimb47090679 (registering DOI) - 24 Aug 2025

Abstract

Cervical cancer screening plays a crucial role in preventing invasive disease through early detection of high-grade lesions. However, traditional cytology and histology often fail to reliably differentiate between transient HPV infections and those likely to progress. This study investigates the feasibility of integrating molecular HPV testing into histopathological workflows using FFPE tissue samples to improve diagnostic precision. A retrospective analysis was conducted on 55 FFPE cervical specimens from patients undergoing colposcopy with biopsy or conization. The workflow included automated DNA extraction and real-time PCR-based HPV genotyping with the Seegene Anyplex II HPV28 assay. HPV DNA was detected in 56.4% of samples, with 21 genotypes, including multiple high-risk types. High viral loads correlated with high-grade lesions, supporting the clinical value of HPV quantification. Compared to histology, molecular analysis reduced potential overdiagnosis by confirming HPV absence in morphologically suspicious but HPV-negative lesions. Integrating viral load and genotyping improved risk stratification, optimizing colposcopy referrals and reducing unnecessary follow-ups. This study introduces a novel, fully automated molecular workflow applicable to FFPE samples, enhancing cervical cancer screening beyond traditional methods. Although based on a limited sample, the findings support the method’s potential for broader implementation and further validation in multicenter settings. Full article

(This article belongs to the Special Issue Molecular Mechanism and Advances in Gynecological Pathology: From Bench to Bedside)

20 pages, 2397 KiB

Open AccessReview

Research Progress on the Regulatory Mechanism of the Waxy Gene in Rice Starch Synthesis

by Fei Chen, Yunsheng Song, Yi Jiang, Penghui Cao, Yajie Yu, Minghui Dong, Yulin Xie, Caiyong Yuan, Yongliang Zhu and Zhongying Qiao

Curr. Issues Mol. Biol. 2025, 47(9), 678; https://doi.org/10.3390/cimb47090678 (registering DOI) - 23 Aug 2025

Abstract

Starch serves as a crucial storage substance in both cereal crops and root/tuber crops, with its composition and properties determining the quality of storage organs. The Waxy (Wx) gene, encoding a key enzyme in starch biosynthesis, plays a pivotal role in this metabolic pathway. However, existing reviews seldom systematically elaborate on Wx gene regulatory mechanisms from the perspective of intrinsic molecular networks. Focusing on the model crop rice, this article synthesizes research advances in Wx-mediated starch biosynthesis regulation over the past decade. We analyze the structural features of the Wx gene and factors influencing its regulatory function during starch synthesis. In conclusion, future research directions are proposed to provide references for Wx gene studies in other crops, as well as theoretical foundations for rice varietal improvement and molecular design breeding. Full article

(This article belongs to the Section Molecular Plant Sciences)

15 pages, 6599 KiB

Open AccessArticle

Low Expression of Selenoprotein S Modulates Osteogenic Differentiation Through Bidirectional Regulation of the SP7–HSP47/COL1A1/SPARC Axis

by Hao Wu, Yun-Shan Zhao, Chun-Shen Li, Jing-Yi Shi, Yi Li, Liang-Qiu-Yue Zhong, Yan Liu and Xi Chen

Curr. Issues Mol. Biol. 2025, 47(9), 677; https://doi.org/10.3390/cimb47090677 (registering DOI) - 23 Aug 2025

Abstract

Previous studies revealed that low expression of Selenoprotein S (SELS) could enhance osteogenic differentiation, but the underlying mechanisms remain unclear. In this study, we aimed to elucidate the role of SELS and its transcription-factor-based regulatory mechanism during osteogenic differentiation. In comparison with 12-week-old mice, which represent the stage of stable osteogenic differentiation, 3-week-old mice, representing the active ossification stage, showed significantly higher levels of SELS in the mandible. Transcriptomic analysis revealed that SELS is primarily associated with extracellular matrix organization and collagen biosynthesis during mandibular development. In bone marrow mesenchymal stem cells (BMSCs) with SELS knockdown, SP7 levels were elevated after 7 days of osteogenic induction in vitro. Consistently, immunohistochemical and immunofluorescence staining confirmed increased SP7 expression in the mandibles of 7-week-old Sels knockout mice. Dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) analysis demonstrated that SP7 directly binds to the heat shock protein 47 (HSP47) promoter and negatively regulates its transcription. Consequently, upregulation of SP7 following SELS knockdown led to downregulation of HSP47 and concurrent upregulation of the SP7 downstream targets, collagen type I alpha 1 chain (COL1A1) and Secreted protein acidic and rich in cysteine (SPARC). SELS expression is upregulated during active osteogenesis. Low expression of SELS regulates osteogenic differentiation in a bidirectional and fine-tuned manner through the SP7–HSP47/COL1A1/SPARC axis. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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16 pages, 2672 KiB

Open AccessReview

Conformational and Functional Properties of the Bioactive Thiosemicarbazone and Thiocarbohydrazone Compounds

by Nikitas Georgiou, Ektoras Vasileios Apostolou, Stamatia Vassiliou, Demeter Tzeli and Thomas Mavromoustakos

Curr. Issues Mol. Biol. 2025, 47(9), 676; https://doi.org/10.3390/cimb47090676 - 22 Aug 2025

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Abstract

Thiosemicarbazones and thiocarbohydrazones are key sulfur-containing organic compounds known for their diverse biological, pharmaceutical, and industrial applications. Beyond their well-established therapeutic potential, their strong chelating ability allows them to form stable complexes with transition metals, enabling uses in catalysis, corrosion inhibition, and dyeing processes. Their structural characteristics and dynamic conformations critically influence both biological activity and industrial performance, making nuclear magnetic resonance (NMR) spectroscopy an indispensable tool for their analysis. This review provides a comprehensive overview of the conformational and functional properties of bioactive thiosemicarbazones and thiocarbohydrazones, with a focus on how experimental NMR techniques are used to investigate their conformational behavior. In addition to experimental findings, available computational data are discussed, offering complementary insights into their structural dynamics. The integration of experimental and theoretical approaches offers a robust framework for predicting the behavior and interactions of these compounds, thereby informing the rational design of novel derivatives with improved functionality. By highlighting key structural features and application contexts, this work addresses a critical gap in the current understanding of these promising agents across both biomedical and industrial domains. Full article

(This article belongs to the Section Bioorganic Chemistry and Medicinal Chemistry)

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