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{"title":"RNA G-quadruplexes: emerging regulators of gene expression and therapeutic targets.","authors":"Zukela Ruzi, Wei Zha, Huang Yuan Yuan, Jiaorui Liu","doi":"10.1007/s10142-025-01656-4","DOIUrl":"https://doi.org/10.1007/s10142-025-01656-4","url":null,"abstract":"<p><p>RNA G-quadruplexes (rG4s) are non-canonical, four-stranded secondary structures formed by guanine-rich RNA sequences. These dynamic elements have garnered significant attention for their critical roles in regulating gene expression, including translation, alternative splicing, mRNA localization, and stability. This review synthesizes recent progress in understanding the structural determinants and formation dynamics of rG4s, highlighting the contributions of sequence motifs, ionic conditions, and RNA-binding proteins to their stability and function. Functional studies reveal that rG4s modulate key oncogenic transcripts (e.g., MYC, BCL2), contribute to splicing regulation, and influence intracellular RNA trafficking. In pathological contexts, rG4s have been implicated in the molecular etiology of cancers, neurodegenerative diseases such as amyotrophic lateral sclerosis and Fragile X syndrome, and viral replication mechanisms in pathogens including HIV and SARS-CoV-2. Advances in high-throughput techniques, such as G4-seq, rG4-seq, and live-cell imaging, have facilitated the global identification and characterization of rG4s in physiological and disease settings. Moreover, the therapeutic targeting of rG4s using small molecules holds promise for selective gene regulation and biomarker development. Comparative analyses across in vitro, in vivo, and clinical studies underscore the cell-type-specific and context-dependent roles of rG4s, especially in mediating stress responses and apoptosis. Despite methodological limitations and challenges in achieving targeted delivery, rG4s represent a compelling frontier for precision medicine. This review outlines current insights and future directions toward harnessing rG4 biology for therapeutic innovation.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"143"},"PeriodicalIF":3.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design strategies, structural insights, and biological potential of amyloid-beta inhibitors in Alzheimer's disease.","authors":"Mridul Guleria, Arprita Malhan, Ghanshyam Teli, Nidhi Bisht, Subheet Kumar Jain","doi":"10.1007/s11030-025-11278-4","DOIUrl":"https://doi.org/10.1007/s11030-025-11278-4","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is an insidious neurodegenerative condition characterized by dementia, cognitive decline, and eventual mortality. The pathogenesis of AD is complex, influenced by multiple factors including neurotransmitter deficiencies, particularly acetylcholine (ACh) and the dysregulation of mental homeostasis, reactive oxygen species (ROS), and amyloid-beta (Aβ) peptide accumulation. The latter is firmly linked to the formation of neurofibrillary tangles (NFTs) and amyloid plaques in the cortical and hippocampal regions, which are hallmarks of the disease pathology. Recent advancements in therapeutic strategies have focused on inhibiting the amyloid-beta peptide, a key contributor to AD progression. This study explores the development of novel amyloid-beta inhibitors and their biological activities, focusing on the synthesis of radiolabeled compounds used in the diagnosis and treatment of Alzheimer's disease. Additionally, we explore the roles of crucial enzymes such as Electrophorus electricus acetylcholinesterase (eeAChE), human acetylcholinesterase (hAChE), and human butyrylcholinesterase (hBuChE) in the disease's neurochemical landscape. The goal of this review is to furnish the scientific community with insight into the design of innovative amyloid imaging agents. These agents are based on diverse scaffolds including flavone, pyrimidine, benzimidazole, imidazole, pyridine, pyrrole, quinoline, indanone, acridine, and peptide-based derivatives, serving as core structures for further research and development. This comprehensive evaluation not only elucidates the molecular underpinnings of AD but also propels forward the quest for efficacious diagnostic and therapeutic tools.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-cancer activity of the glycyrrhetinic acid derivatives with an inhibitory inflammatory microenvironment.","authors":"Jianrong Liu, Tianbo Wu, Wei Li, Quanyi Zhao, Dian He","doi":"10.1007/s11418-025-01926-2","DOIUrl":"https://doi.org/10.1007/s11418-025-01926-2","url":null,"abstract":"<p><p>The tumor inflammatory microenvironment plays an important role in tumor development, and the compounds which modulate tumor microenvironment can be able to accelerate tumor cell death. Here, compound 1 was screened and evaluated through both inhibiting cancer cell proliferation and alleviating the inflammation in microenvironment. In the anti-cancer cell proliferation assay, compound 1 displayed strong proliferative inhibition against all six cell lines, with IC₅₀ values in the range 2-6 μM; among them, the HCT116 cell line was the most sensitive to compound 1. Second, compound 1 showed better inflammatory activities in RAW264.7 cell model than the control GA and 5-FU; it not only decreased the NO level in a concentration-dependent manner, but also reduced the TLR4, HMGB1, IL-1β, TNF-α, iNOS and COX-2 levels; moreover, compound 1 also strongly inhibited NO produce in A549, HEPG2, and HCT116 cells, and it displayed the best for HCT116 cells, with an IC₅₀ value of 2.04 ± 0.68 μM. Third, compound 1 decreased the MMP and increased ROS levels in HCT116 cells; and it upregulated the expression levels of Bax and Cyt-C, and downregulated the Bcl-2 level, finally activating caspase-3 to promote the HCT116 cells apoptosis. This indicates compound 1 had an anti-HCT116 activity possibly by inhibiting the inflammatory factors in microenvironment, as well as by inducing HCT116 cells apoptosis. In animal tests, compound 1 reduced the volume and weight of tumor, indicating it has an obvious anti-tumor effect. Overall, compound 1 is a multi-target drug for the treatment of colon cancer, and it has the potential to be an anti-colon cancer drug candidate.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the antineoplastic potential of α-mangostin in breast cancer.","authors":"Daniela Amador-Martínez, Mizraim Flores, Rafael Vargas-Castro, Rocío García-Becerra, Euclides Avila, Lorenza Díaz, Janice García-Quiroz","doi":"10.1007/s13659-025-00528-5","DOIUrl":"https://doi.org/10.1007/s13659-025-00528-5","url":null,"abstract":"<p><p>Among women, breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related mortality globally. Despite improvements in early detection and diagnosis, some risk factors have been on the rise, including the decline in birth rate, the use of oral contraceptives, and the escalation in alcohol consumption and obesity. Thus, there is an imperative urgent need to expand accessible prevention and treatment options for breast cancer. Regarding these tumors, several natural compounds have shown efficacy in slowing or preventing their progression, offering a promising therapeutic alternative. Among these, α-mangostin, a xanthone derived from mangosteen, has demonstrated promising antitumor effects against different malignancies, particularly breast cancer. The mechanisms involved in α-mangostin´s therapeutic effects include downregulation of oncogenic ion channels, modulation of cell cycle progression, suppression of oncogene expression, and interference with steroid and growth factor receptors signaling. This review thoroughly explores these mechanisms, as well as updates information on α-mangostin chemical structure and its potential as a coadjuvant to conventional breast cancer therapies. Furthermore, we provide scientifically supported insights for the development of clinically applicable α-mangostin-based treatments, highlighting the robust body of evidence supporting its cancer-fighting properties, despite the absence of clinical studies to date.</p>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"15 1","pages":"43"},"PeriodicalIF":4.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Sarah R. Zelle,&nbsp;W. Hayes McDonald,&nbsp;Kristie L. Rose,&nbsp;Hassane S. Mchaourab and Kevin L. Schey*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 7","pages":"XXX-XXX 962–968"},"PeriodicalIF":3.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/jasms.5c00087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complex Interplay of Tandem, Segmental, Whole Genome Duplication, and Re-organization Drives Expansion of SAUR Gene Family in Brassicaceae.","authors":"Richa Shukla, Ekta Pokhriyal, Sandip Das","doi":"10.1007/s10528-025-11167-3","DOIUrl":"https://doi.org/10.1007/s10528-025-11167-3","url":null,"abstract":"<p><p>Members of the SAUR, small auxin upregulated RNA, gene family initially identified as auxin inducible, mediate diverse developmental and adaptive processes in plants. Inspite of their importance, identification and analysis of homologs from Brassica juncea, a major oilseed crop, is lacking. Additionally, investigations into organisational complexity and evolutionary past across Brassicaceae remain to be investigated. The present study was therefore designed to identify members of the SAUR gene family in B. juncea, reconstruct phylogenetic relationship, and analyse the history of expansion of the SAUR gene family across Brassicaceae. Genome-wide in-silico analysis allowed us to identify 237 SAUR genes in the allotetraploid B. juncea (AABB genome), which are distributed in a clustered manner among all 18 chromosomes of the B. juncea genome. Comparative analysis with the diploid parents- B. rapa (AA) and B. nigra (BB) revealed conserved organisation pattern. A striking feature of SAUR genes is intronless nature of most members. Comparative analysis revealed ten clusters of tandemly arrayed genes (TAGs) in Arabidopsis thaliana; two of these clusters were lost, and 33 clusters that are orthologous to the rest of A. thaliana clusters were identified from B. juncea genome. Organisational complexity revealed the presence of putative bidirectional promoters between some SAUR genes. Phylogenetic reconstruction shows several SAUR genes of A. thaliana and B. juncea forming separate clades, indicating lineage-specific expansion. Inclusion of homologs from across Brassicaceae allowed us to perform comparative synteny analysis and hypothesize local duplications being responsible for the tandem organisation, and segmental duplications as driving mechanism for large-scale expansion. The present study allowed us to catalog homologs of the SAUR gene family in B. juncea. This study thus forms the foundation for functional characterization involving transcriptional regulation, generation, and analysis of reverse genetic models toward understanding their role in plant growth and development.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orthogonal alignment of multilayered MC3T3-E1 cells induced by cyclic stretch.","authors":"Shuichiro Suzuki, Ken Imajo, Junfeng Wang, Jeonghyun Kim, Eijiro Maeda, Kazuaki Nagayama, Takeo Matsumoto","doi":"10.1007/s10237-025-01978-z","DOIUrl":"https://doi.org/10.1007/s10237-025-01978-z","url":null,"abstract":"<p><p>When cyclic stretch is applied to a monolayer of cells cultured on an elastic substrate, many types of cells align in the direction perpendicular to the stretch or along the direction of minimal substrate strain. However, the behavior of multilayer cells under cyclic stretch remains unclear. In this study, we cultured MC3T3-E1 osteoblast-like cells at high density to form multilayer cells and subjected them to cyclic stretch with an amplitude of 10% at 1 Hz. We found that the lower layer cells aligned in the direction of the stretch after 12 h, whereas the upper layer cells aligned perpendicular to the direction of stretch after 24 h. The 10% cyclic stretch was transmitted to the upper layer cells as approximately 5% at the onset of the stretch and increased over time, reaching 7% at 12 h when the lower layer cells completed alignment in the direction of stretch. This suggests that sufficient cyclic stretch transmitted to the upper layer led to the alignment of the upper layer cells in the perpendicular direction after 12 h. On the other hand, reducing intracellular tension with Y-27632 caused cells in both upper and lower layers to align in the direction of stretch. In contrast, increasing intracellular tension with calyculin A eliminated significant alignment in both layers. These findings indicate that cell alignment is closely related to intracellular tension and that the alignment of the lower layer cells in the direction of stretch may be due to a decrease in intracellular tension.</p>","PeriodicalId":489,"journal":{"name":"Biomechanics and Modeling in Mechanobiology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an NMR-based quantification method for the main components in VAE-type adhesives/emulsions.","authors":"Jiajia Niu, Aimin He, Feng Gao, Zhenhua Yu, Jiehui Li, Yang Liu, Hongling Hao, Jingzheng Chen, Fengmei Zhang, Chen Chen, Liqing Yue","doi":"10.1186/s13065-025-01556-5","DOIUrl":"https://doi.org/10.1186/s13065-025-01556-5","url":null,"abstract":"<p><p>It is important to accurately test the content of the main components (i.e., oxyacetyl, vinyl, and vinyl alcohol) of VAE-type adhesives/emulsions. In this study, we first investigated the solubility of dried VAE samples. Dimethyl sulfoxide (DMSO) was the best solvent tested, and at a sample concentration of 10,000 µg/mL, complete dissolution was achieved after 3 h of ultrasonication. Second, different chemical shifts of protons in the ¹H NMR spectrum of VAE samples were assigned as follows: 2.01 ppm for CH₃ of oxyacetyl groups, 1.5-1.8 ppm for the backbone CH₂ connected to vinyl alcohol or oxyacetyl groups, and 1.2 ppm for the backbone CH₂. Based on these assignments, an ¹H NMR normalization-based quantification method was established. Meanwhile, correction factors of each VAE functional group relative to the internal standard benzyl benzoate were calculated to establish an ¹H NMR internal standard-based quantification method. For the vinyl acetate monomer that was tested as a proxy for the oxyacetyl group, the ¹H NMR internal standard-based quantification method yielded a closer result (37.44%) to the classical method (37.30%) than the normalization-based method. The method exhibited good repeatability and reproducibility (repeatability RSD < 5%, reproducibility RSD: vinyl and oxyacetyl < 5%, vinyl alcohol < 11.24%). In contrast, a ¹³C NMR internal standard-based quantification method was deemed unsuitable for the quantitative analysis of VAE main components due to its high sample concentration requirements, lengthy test durations, and tendency to underestimate the actual contents. Finally, a ¹H NMR internal standard-based quantification method was established for the determination of the main components of VAE-type adhesives/emulsions.</p>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":"186"},"PeriodicalIF":4.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Weiwen Sun,&nbsp;Xiaotong Geng,&nbsp;Jihong Xu,&nbsp;Yong Huang,&nbsp;Shifa Zhong*,&nbsp;Lushi Lian* and Xiaohong Guan,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 7","pages":"XXX-XXX 962–968"},"PeriodicalIF":3.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/jasms.5c00088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing heavy metal pollution and livestock health risks in sewage water-irrigated fodder systems: a comprehensive study.","authors":"Mahendra Prasad, Sonu Kumar Mahawer, M M Das, M Vassanda Coumar, J K Saha, D R Palsaniya","doi":"10.1007/s10661-025-14327-5","DOIUrl":"https://doi.org/10.1007/s10661-025-14327-5","url":null,"abstract":"<p><p>Sewage water (SW) irrigation is widely used in developing countries, particularly in arid and semi-arid regions, as a cost-effective method for crop production. However, it poses significant ecological and health risks owing to the presence of heavy metals (HMs), necessitating effective management strategies. This study assesses the impact of mixing SW with groundwater (GW) in various ratios (SW₀: 0%SW, SW₂₅: 25%SW, SW₅₀: 50%SW, SW₇₅: 75%SW, and SW₁₀₀: 100%SW) on fodder productivity, HMs accumulation, and associated risks to livestock in Jhansi, Uttar Pradesh, India. Over three years, SW irrigation improved soil fertility and increased fodder yields by 6-25%. However, it led to elevated levels of HMs in the soil-fodder system. Among the crops studied, oat showed the lowest bioaccumulation compared to cowpea, maize, and berseem, with Pb levels exceeding permissible limits in the SW₁₀₀ treatment. Most tested crops exceeded WHO/FAO limits for HMs, except for Cr and Cd in the SW₂₅ treatment. Pollution index values categorized all crops as \"severely\" to \"heavily polluted\", except for oat. Ecological risk indices were low for SW₀ to SW₅₀, with Cd presenting the highest ecological risk (38-69%). The transfer factor (TF) for Cr, Ni, and Cd was <1, while Pb exceeded 1 for all crops. The health risk index (HRI) for Pb was also >1, signaling health risks to immune function, productivity, and reproductive performance in livestock consuming SW-irrigated fodder. A blend of lesser metal-accumulating fodder crops and a 1:3 SW: GW dilution ratio can effectively minimize these risks. Our findings provide baseline information to policymakers, environmentalists, and livestock keepers for formulating strategic mitigation plans to minimize the potential future risks of HMs pollution in the soil-fodder-livestock continuum.</p>","PeriodicalId":544,"journal":{"name":"Environmental Monitoring and Assessment","volume":"197 8","pages":"839"},"PeriodicalIF":2.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}