Frontiers in bioscience (Landmark edition)最新文献

{"title":"Atomized Neutrophil Membrane-coated MOF Nanoparticles for Direct Delivery of Dexamethasone for Severe Pneumonia.","authors":"Yixiao Yang, Lizhen Yan, Han Zhang, Chuanguang Xiao, Kai Wang","doi":"10.31083/FBL26721","DOIUrl":"https://doi.org/10.31083/FBL26721","url":null,"abstract":"<p><strong>Background: </strong>Dexamethasone has proven life-saving in severe acute respiratory syndrome (SARS) and COVID-19 cases. However, its systemic administration is accompanied by serious side effects. Inhalation delivery of dexamethasone (Dex) faces challenges such as low lung deposition, brief residence in the respiratory tract, and the pulmonary mucus barrier, limiting its clinical use. Neutrophil cell membrane-derived nanovesicles, with their ability to specifically target hyper-activated immune cells and excellent mucus permeability, emerge as a promising carrier for pulmonary inhalation therapy.</p><p><strong>Methods: </strong>We designed a novel UiO66 metal-organic framework nanoparticle loaded with Dex and coated with neutrophil cell membranes (UiO66-Dex@NMP) for targeted therapy of severe pneumonia. This was achieved by loading Dex into UiO66 pores and subsequently coating with neutrophil membranes for functionalization.</p><p><strong>Results: </strong>Drug release experiments revealed UiO66-Dex@NMP to exhibit favorable sustained-release properties. Additionally, UiO66-Dex@NMP demonstrated excellent targeting capabilities both <i>in vitro</i> and <i>in vivo</i>. In a mouse model of lipopolysaccharide (LPS)-induced pneumonia, UiO66-Dex@NMP significantly reduced lung inflammation compared to both the control model and Dex administered via inhalation. Histopathological analysis further confirmed UiO66-Dex@NMP's ability to alleviate lung tissue damage.</p><p><strong>Conclusions: </strong>UiO66-Dex@NMP represents a novel and safe inhaled delivery carrier for Dex, offering valuable insights into the clinical management of respiratory diseases, including severe pneumonia.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"26721"},"PeriodicalIF":3.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monocyte and Macrophage in Follicular Liquid: Predictive Markers of Embryo Quality in Women with Obesity and Infertility.","authors":"Evgeny D Merkulov, Anastasia V Prozorova, Iuliia G Samoilova, Dmitry A Svarovsky, Kira A Sidorenkova, Liudmila V Spirina, Marina N Stakheeva, Oxana S Timofeeva, Ilya A Petrov","doi":"10.31083/FBL26660","DOIUrl":"https://doi.org/10.31083/FBL26660","url":null,"abstract":"<p><strong>Background: </strong>Over the past five years, the pregnancy rate in assisted reproductive technology (ART) programs in Russia has remained relatively stable. The aim of this study was to assess the distribution of monocyte and macrophage subsets in the blood and follicular fluid of infertile women undergoing assisted reproductive technology.</p><p><strong>Methods: </strong>The study involved 45 women with a mean age of 35 ± 4.66 years. Monocytes and macrophages were identified using flow cytometry.</p><p><strong>Results: </strong>We observed a decrease in the CD68+CD163+CD206+ and the CD68+CD163-CD206+ cells in patients with a body mass index (BMI) >25 by 0.19 times and 6.56 times, respectively, compared to the group with a BMI <25 (<i>p</i> = 0.031). Patients with fair oocyte quality had 3.6 times more oocytes than those with poor quality (<i>p</i> = 0.010). The relative content of CD14+163-206+ monocytes was found to be 24.15 times higher in the follicular fluid of women with poor embryo quality compared to the group with good embryos (<i>p</i> = 0.010). We also noted that the number of oocytes increased in women with male factor infertility (<i>p</i> = 0.020) and those with unspecified infertility when compared to tubal infertility. An increase in the relative content of CD14+163+206+ in the blood was higher in women with other causes of female infertility compared to those with male factor infertility (<i>p</i> = 0.010). The relative content of M2-monocytes (CD14+163+206-) in the blood was 4.38 times higher in women with male factor infertility than in women with unexplained infertility (<i>p</i> = 0.010).</p><p><strong>Conclusions: </strong>A critical component of the inflammatory reaction in patients undergoing <i>in vitro</i> fertilization (IVF) involves more than just the activation of pro-inflammatory cells in response to ovarian stimulation. Our research shows that changes in the distribution of monocytes and macrophages can influence embryo implantation success and pregnancy outcomes in women. These processes are influenced by various infertility-related factors, including those mentioned above. However, these findings are preliminary and require further investigation.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"26660"},"PeriodicalIF":3.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERK1/2 Inhibition Alleviates Diabetic Cardiomyopathy by Suppressing Fatty Acid Metabolism.","authors":"Erin McLean, Caroline De Roo, Annabel Maag, Megan Coble, Jefferson Cano, Ruijie Liu","doi":"10.31083/FBL26700","DOIUrl":"https://doi.org/10.31083/FBL26700","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus is associated with morphological and functional impairment of the heart primarily due to lipid toxicity caused by increased fatty acid metabolism. Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) have been implicated in the metabolism of fatty acids in the liver and skeletal muscles. However, their role in the heart in diabetes remains unclear. In this study, we tested our hypothesis that pharmacological inhibition of ERK1/2 alleviates cardiac remodeling in diabetic mice through a reduction in fatty acid metabolism.</p><p><strong>Methods: </strong>ERK1/2 phosphorylation in diabetes was determined both <i>in vitro</i> and <i>in vivo</i>. H9C2 cells were subjected to high glucose, high palmitic acid, or both high glucose and palmitic acid. <i>db/db</i> and streptozotocin (STZ)-induced diabetic mice were analyzed for ERK1/2 phosphorylation levels as well as the effects of U0126 treatment on cardiac remodeling. Administration of STZ and U0126 in mice was performed via intraperitoneal injection. Blood glucose levels in mice were measured using a glucometer. Mouse heart total RNAs were purified for reverse transcription. Real-time polymerase chain reaction (PCR) analysis of the messenger ribonucleic acid (mRNA) expression was performed for hypertrophy (<i>ANF</i>, <i>BNP</i>, and <i>βMHC</i>), fibrosis (<i>Col3α1</i>), and fatty acid metabolism genes (<i>PPARα</i>, <i>CPT1A</i>, and <i>FACS</i>). Interstitial fibrosis of the myocardium was analyzed using Masson's trichrome staining of the paraffin-embedded tissues.</p><p><strong>Results: </strong>ERK1/2 phosphorylation was significantly increased in diabetic conditions. Inhibition of ERK1/2 by U0126 in both streptozotocin-induced diabetic mice and <i>db/db</i> mice resulted in a significant reduction in the expression of genes associated with hypertrophy and fibrosis. In contrast, elevated phosphorylation of ERK1/2 in <i>Dusp6/8</i> knockout (DKO) mice resulted in fibrosis. Mechanistically, ERK1/2 activation enhanced the expression of fatty acid metabolism genes <i>PPARα</i>, <i>CPT1A</i>, and <i>FACS</i> in the heart, which was reversed by U0126 treatment.</p><p><strong>Conclusion: </strong>ERK1/2 are potential therapeutic targets for diabetic cardiomyopathy by modulating fatty acid metabolism in the heart.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"26700"},"PeriodicalIF":3.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SUMO-Specific Peptidase 5 Promotes Oesophageal Squamous Cell Carcinoma Growth through the NF-κB-<i>SLC1A3</i> Axis.","authors":"Chaoxiang Du, Yunfan Hu, Xinyu Yang, Zhe Zhang, Jianmin Gu, Tao Zhang, Renfeng Wang, Shaoyuan Zhang, Lijie Tan, Guiping Yu","doi":"10.31083/FBL27047","DOIUrl":"https://doi.org/10.31083/FBL27047","url":null,"abstract":"<p><strong>Background: </strong>This study investigates the role of small ubiquitin-like modifier (SUMO)-specific peptidase 5 (SENP5), a key regulator of SUMOylation, in esophageal squamous cell carcinoma (ESCC), a lethal disease, and its underlying molecular mechanisms.</p><p><strong>Methods: </strong>Differentially expressed genes between ESCC mouse oesophageal cancer tissues and normal tissues were analysed via RNA-seq; among them, SENP5 expression was upregulated, and this gene was selected for further analysis. Immunohistochemistry and western blotting were then used to validate the increased protein level of SENP5 in both mouse and human ESCC samples. The Kaplan‒Meier method and multivariate analysis were used to analyse the relationship between SENP5 expression and ESCC prognosis. Stable SENP5-knockdown (KD) cell lines and conditional knockout (cKO) mice were established to verify the biological function of SENP5. Further RNA-seq comparisons between short hairpin SENP5 (shSENP5)- and short hairpin negative control (shNC)-transfected ESCC cell lines were conducted, and the nuclear factor kappa B (NF-κB)-<i>SLC1A3</i> axis was identified through bioinformatics analysis. The correlation of SENP5 with signalling pathway components was validated via real-time quantitative PCR (qPCR), western blotting (WB), and immunoprecipitation.</p><p><strong>Results: </strong>Our study revealed that SENP5 was upregulated in human and mouse ESCC samples, and clinical data analysis revealed a correlation between high SENP5 expression and poor patient prognosis. SENP5 knockdown inhibited tumorigenesis and growth <i>in vivo</i> and suppressed the proliferation, migration, and invasion of ESCC cell lines <i>in vitro</i>. Our study also revealed that SENP5 knockdown enhanced the SUMO1-mediated SUMOylation of NF-kappa-B inhibitor alpha (IκBα), thereby inhibiting the activation of the NF-κB-<i>SLC1A3</i> axis, which subsequently suppresses ESCC cell energy metabolism and impedes ESCC progression.</p><p><strong>Conclusions: </strong>Suppression of SENP5 slows the development of ESCC by inhibiting the NF-κB<i>‒SLC1A3</i> axis through SUMO1-mediated SUMOylation of IκBα. Our research suggests that SENP5 could serve as a prognostic indicator and a target for therapeutic intervention for ESCC patients.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"27047"},"PeriodicalIF":3.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SERT-Deficient Mice Fed Western Diet Reveal Altered Metabolic and Pro-Inflammatory Responses of the Liver: A Link to Abnormal Behaviors.","authors":"Raymond Cespuglio, Anna Gorlova, Konstantin Zabegalov, Kirill Chaprov, Evgeniy Svirin, Kseniia Sitdikova, Alisa Burova, Boris Shulgin, Ksenia Lebedeva, Alexei V Deikin, Sergey Morozov, Tatyana Strekalova","doi":"10.31083/FBL26778","DOIUrl":"https://doi.org/10.31083/FBL26778","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The inheritance of the short &lt;i&gt;SLC6A4&lt;/i&gt; allele, encoding the serotonin transporter (SERT) in humans, increases susceptibility to neuropsychiatric and metabolic disorders, with aging and female sex further exacerbating these conditions. Both central and peripheral mechanisms of the compromised serotonin (5-HT) system play crucial roles in this context. Previous studies on SERT-deficient (Sert&lt;sup&gt;-/-&lt;/sup&gt;) mice, which model human SERT deficiency, have demonstrated emotional and metabolic disturbances, exacerbated by exposure to a high-fat Western diet (WD). Growing evidence suggests the significance of hepatic regulatory mechanisms in the neurobiology of central nervous system disorders, supporting the 'liver-brain' concept. However, the relationship between aberrant behavior and hepatic alterations under conditions of SERT deficiency remains poorly investigated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;One-year-old female Sert&lt;sup&gt;-/-&lt;/sup&gt; mice and their wild-type (WT) littermates were subjected to a control diet (CD) or the WD for a duration of three weeks. The WD had a higher caloric content and was characterized by an elevated saturated fat content (21%) compared to the CD (4.5%) and contained 0.2% cholesterol. Mice were evaluated for anxiety-like behavior, exploration and locomotor activity in the open field test, as well as glucose tolerance and histological indicators of hepatic steatosis. Hepatic pro-inflammatory and metabolism-related gene expression and markers of nitrosative stress, were analyzed utilizing real-time polymerase chain reaction (RT-PCR) and correlated with behavioral and histological outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In comparison to unchallenged mice, Sert&lt;sup&gt;-/-&lt;/sup&gt;/WD mutants, but not the WT/WD group, had increased locomotion and anxiety-like behavior, increased hepatic steatosis, and elevated expression of insulin receptor B and pro-inflammatory cytokines interleukin-1β (&lt;i&gt;Il-1&lt;/i&gt;β) and &lt;i&gt;Tnf&lt;/i&gt;, as well as decreased expression of leptin receptor B. The two genotypes displayed distinct gene expression patterns of nitric oxide (NO)-related molecules inducible NO synthase (&lt;i&gt;iNos&lt;/i&gt;) and arginase (&lt;i&gt;Arg2&lt;/i&gt;), insulin receptor-related signaling factors: cluster of differentiation 36 (&lt;i&gt;Cd36&lt;/i&gt;), ecto-nucleotide pyrophosphatase/phosphodiesterase (&lt;i&gt;Enpp&lt;/i&gt;), protein tyrosine phosphatase N1 (&lt;i&gt;Ptpn1&lt;/i&gt;), cytochrome P450 omega-hydroxylase 4A14 (&lt;i&gt;Cyp4a14&lt;/i&gt;), acyl-CoA synthetase 1 (&lt;i&gt;Acsl1&lt;/i&gt;) and phosphatase and tensin homolog (&lt;i&gt;Pten&lt;/i&gt;). Furthermore, there were profound differences in correlations between molecular, histological, and behavioral measurements across the two genotypes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our findings suggest that the genetic deficiency of SERT results in abnormal hepatic pro-inflammatory and metabolic adaptations in response to WD. The significant correlations observed between behavioral measures and pro-inflammatory and metabolic al","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"26778"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HP1 Promotes the Centromeric Localization of ATRX and Protects Cohesion by Interfering Wapl Activity in Mitosis.","authors":"Erchen Zhang, Lei Peng, Kejia Yuan, Zexian Ding, Qi Yi","doi":"10.31083/FBL26426","DOIUrl":"https://doi.org/10.31083/FBL26426","url":null,"abstract":"<p><strong>Background: </strong>α thalassemia/mental retardation syndrome X-linked (ATRX) serves as a part of the sucrose nonfermenting 2 (SNF2) chromatin-remodeling complex. In interphase, ATRX localizes to pericentromeric heterochromatin, contributing to DNA double-strand break repair, DNA replication, and telomere maintenance. During mitosis, most ATRX proteins are removed from chromosomal arms, leaving a pool near the centromere region in mammalian cells, which is critical for accurate chromosome congression and sister chromatid cohesion protection. However, the function and localization mechanisms of ATRX at mitotic centromeres remain largely unresolved.</p><p><strong>Methods: </strong>The clustered regularly interspaced short palindromic repeats with CRISPR-associated protein 9 (CRISPR-Cas9) system and overexpression approaches were employed alongside immunofluorescence to investigate the mechanism of ATRX localization at the centromere. To study the binding mechanism between ATRX and heterochromatin protein 1 (HP1), both full-length and truncated mutants of hemagglutinin (HA)-ATRX were generated for co-immunoprecipitation and glutathione S-transferase (GST)-pull assays. Wild-type ATRX and HP1 binding-deficient mutants were created to investigate the role of ATRX binding to HP1 during mitosis, with the Z-Leu-Leu-Leu-al (MG132) maintenance assay, cohesion function assay, and kinetochore distance measurement.</p><p><strong>Results and conclusions: </strong>Our research demonstrated that HP1α, HP1β, and HP1γ facilitate the positioning of ATRX within the mitotic centromere area through their interaction with the first two [P/L]-X-V-X-[M/L/V] (PxVxL)motifs at the N-terminus of ATRX. ATRX deficiency causes aberrant mitosis and decreased centromeric cohesion. Furthermore, reducing Wapl activity can bypass the need for ATRX to protect centromeric cohesion. These results provide insights into the mechanism of ATRX's centromeric localization and its critical function in preserving centromeric cohesion by reducing Wapl activity in human cells.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"26426"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"tiRNA-Gln-CTG is Involved in the Regulation of Trophoblast Cell Function in Pre-eclampsia and Serves as a Potent Biomarker.","authors":"Yixiao Wang, Xiaohong Ji, Hengmei Shi, Sicong Liu, Hong Yu","doi":"10.31083/FBL26345","DOIUrl":"10.31083/FBL26345","url":null,"abstract":"<p><strong>Background: </strong>Pre-eclampsia (PE) is a gestational disorder that significantly endangers maternal and fetal health. Transfer ribonucleic acid (tRNA)-derived small RNAs (tsRNAs) are important in the progression and diagnosis of various diseases. However, their role in the development of PE is unclear. Consequently, we detected the expression profiles of tsRNAs in the plasma of patients with PE as well as those in the plasma of the healthy control group, and a multiplicity of experiments were conducted with the aim of clarifying their roles in the occurrence and development of PE and the feasibility of serving as predictive biomarkers for this disorder.</p><p><strong>Methods: </strong>High-throughput sequencing of tsRNA in plasma from PE cases was performed to evaluate its potential as a diagnostic or therapeutic biomarker. The function of tsRNA in trophoblasts was explored using the HTR-8/SVneo cell line. Plasma from pregnant women with suspected PE was analyzed to assess the potential of tsRNA to act as a predictive marker of PE.</p><p><strong>Results: </strong>High-throughput sequencing of tsRNA was performed on plasma from pregnant women with PE and from healthy pregnant controls. Analysis revealed a significant reduction in the level of tRNA-derived stress-inducing RNA (tiRNA)-Gln-CTG in the plasma (<i>p</i> < 0.001) and placenta (<i>p</i> < 0.001) of pregnant women with PE, suggesting its potential involvement in the development of this condition. tiRNA-Gln-CTG was identified in the cytoplasm and nucleus of HTR-8/SVneo cells. <i>In vitro</i> experiments revealed that tiRNA-Gln-CTG influences the proliferation, cycling, migration, and invasion of HTR-8/SVneo cells, possibly by targeting the 3'UTR region of thrombospondin-2 messenger ribonucleic acid (mRNA) for degradation. Extracellular vesicle (EV) carriers may mediate the level of tiRNA-Gln-CTG in the circulation. Y-box binding protein-1 (YBX1) may be involved in loading tiRNA-Gln-CTG into EVs. The sensitivity of low tiRNA-Gln-CTG levels for predicting the onset of PE in suspected cases was 91.7% within 1 week of delivery, 85.7% within 4 weeks of delivery, and 89.3% before delivery, with corresponding specificities of 84.5%, 79.2%, and 73.4%, respectively.</p><p><strong>Conclusions: </strong>tiRNA-Gln-CTG significantly influences trophoblast function and is associated with the development of PE. It can serve as an effective biomarker for predicting PE progression within one week of delivery in women with suspected PE.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"26345"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin Bs as Potent Anticancer Agents through MMP-2/9 Regulation.","authors":"Ha Vy Thi Vo, Namdoo Kim, Hyuck Jin Lee","doi":"10.31083/FBL24072","DOIUrl":"https://doi.org/10.31083/FBL24072","url":null,"abstract":"<p><p>In recent years, the role of coenzymes, particularly those from the vitamin B group in modulating the activity of metalloenzymes has garnered significant attention in cancer treatment strategies. Metalloenzymes play pivotal roles in various cellular processes, including DNA repair, cell signaling, and metabolism, making them promising targets for cancer therapy. This review explores the complex interplay between coenzymes, specifically vitamin Bs, and metalloenzymes in cancer pathogenesis and treatment. Vitamins are an indispensable part of daily life, essential for optimal health and well-being. Beyond their recognized roles as essential nutrients, vitamins have increasingly garnered attention for their multifaceted functions within the machinery of cellular processes. In particular, vitamin Bs have emerged as a pivotal regulator within this intricate network, exerting profound effects on the functionality of metalloenzymes. Their ability to modulate metalloenzymes involved in crucial cellular pathways implicated in cancer progression presents a compelling avenue for therapeutic intervention. Key findings indicate that vitamin Bs can influence the activity and expression of metalloenzymes, thereby affecting processes such as DNA repair and cell signaling, which are critical in cancer development and progression. Understanding the mechanisms by which these coenzymes regulate metalloenzymes holds great promise for developing novel anticancer strategies. This review summarizes current knowledge on the interactions between vitamin Bs and metalloenzymes, highlighting their potential as anticancer agents and paving the way for innovative, cell-targeted cancer treatments.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"24072"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Androgenic Anabolic Steroids Cause Thiol Imbalance in the Vascular Endothelial Cells.","authors":"Halszka Ponamarczuk, Maria Światkowska, Marcin Popielarski","doi":"10.31083/FBL26542","DOIUrl":"https://doi.org/10.31083/FBL26542","url":null,"abstract":"<p><strong>Background: </strong>Androgenic anabolic steroids (AASs) are synthetic drugs structurally related to testosterone, with the ability to bind to androgen receptors. Their uncontrolled use by professional and recreational sportspeople is a widespread problem. AAS abuse is correlated with severe damage to the cardiovascular system, including changes in homeostasis and coagulation disorders. AASs alter vascular function by blocking nitric oxide (NO)-mediated dilation, impairing endothelial growth and by potentiating vasoconstrictor signals.</p><p><strong>Methods: </strong>This paper demonstrated that long-term use of AASs (nandrolone and boldenone), negatively affects the basic cell functions of vascular endothelial cells. The susceptibility of endothelial cells to AASs depends on the expression of androgen receptors, although cells without androgen receptors can also be affected by high doses of AASs to a limited extent. Seven-day incubation with AASs diminishes endothelial cell proliferation and migration (determined by transwell and scratch migration assay) and monolayer formation (using transendothelial electrical resistance assay).</p><p><strong>Results: </strong>Disturbances in cell function were accompanied by downregulation of peroxiredoxins (PRDX1 and PRDX2), involved in maintaining the thiol-disulphide balance. In addition, AASs increased oxidation of the non-enzymatic thiol buffer, glutathione (GSH), reduced secretion of thiol oxidoreductase protein disulphide isomerase (PDI) from endothelial cells and affected the thiol pattern of PDI.</p><p><strong>Conclusions: </strong>These changes may be related to a thiol-disulfide imbalance and vascular endothelium dysfunction, that are often correlated with abnormal platelet aggregation, inflammation, increased vascular permeability, and vascular smooth muscle cell proliferation-all of which are observed in athletes who abuse AASs.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"26542"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Winery By-Products <i>In Vitro</i> and <i>In Vivo</i> Effects on Atherothrombotic Markers: Focus on Platelet-Activating Factor.","authors":"Maria Choleva, Smaragdi Antonopoulou, Elizabeth Fragopoulou","doi":"10.31083/FBL25859","DOIUrl":"https://doi.org/10.31083/FBL25859","url":null,"abstract":"<p><p>Platelet aggregation and inflammation play a crucial role in atherothrombosis. Wine contains micro-constituents of proper quality and quantity that exert cardioprotective actions, partly through inhibiting platelet-activating factor (PAF), a potent inflammatory and thrombotic lipid mediator. However, wine cannot be consumed extensively due to the presence of ethanol. Alternatively, winery by-products are abundant in similar-to-wine micro-constituents that could be used in food fortification and dietary supplements. Also, the vinification process produces millions of tons of by-products worldwide, posing an environmental matter of waste management. Therefore, the purpose of this literature review is to update the existing data concerning the <i>in vitro</i> anti-platelet and anti-inflammatory properties of winery by-product extracts and their possible health effects through controlled clinical trials in humans, specifically focused on their effects on PAF's actions. Data from <i>in vitro</i> studies report that winery by-product compounds are able to inhibit platelet aggregation against several aggregation factors, as well as to downregulate inflammatory markers. Among their actions, extracts or phenolic compounds present in winery by-products inhibit PAF's actions, a potent inflammatory and thrombotic mediator. Similar conclusions have been drawn from human supplementation studies, which suggest that winery by-product extracts may have beneficial biological effects on the cardiovascular system. Evidence from long-term studies shows that consumption may lower total and low density lipoprotein (LDL) cholesterol, improve insulin sensitivity, decrease lipid and protein oxidative damage, enhance antioxidant capacity, and have mild anti-inflammatory action toward reducing cytokine expression and levels. Data from the limited postprandial studies report that the acute consumption of winery by-product extracts improves glycemic response and reduces platelet reactivity to aggregatory stimuli. Although wine extracts and phenolic compounds have been reported to inhibit PAF's actions and reduce the activity of its biosynthetic enzymes, no data exist concerning the influence of winery by-product extracts. In the future, additional long-term randomized controlled trials or postprandial studies are needed to draw definitive conclusions and establish a viable cardioprotective strategy that incorporates the sustainable use of winery by-products.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"25859"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}