Frontiers in bioscience (Landmark edition)最新文献

{"title":"Heterogeneity in Fluorescence-Stained Sperm Membrane Patterns and Their Dynamic Changes Towards Fertilization in Mice.","authors":"Momoka Hirai, Satoshi Kishigami","doi":"10.31083/FBL26784","DOIUrl":"https://doi.org/10.31083/FBL26784","url":null,"abstract":"<p><strong>Background: </strong>Sperm represent a heterogeneous population crucial for male reproductive success. Additionally, sperm undergo dynamic changes during maturation and capacitation. Despite these well-established processes, the complex nature of sperm heterogeneity and membrane dynamics remains elusive. The composition of phospholipids in the sperm membrane changes dynamically during maturation, with their release occurring during capacitation. This study aims to investigate the heterogeneity and dynamic changes in the sperm membrane during maturation and capacitation towards fertilization by visualizing these membrane dynamics.</p><p><strong>Methods: </strong>Sperm were collected from the cauda epididymis or testis of Institute of Cancer Research (ICR) male mice and stained with MemBright dye (commercial name: MemGlow™-560, MG-560), a fluorogenic live-cell membrane probe. Staining was performed either before, during, or after incubation for capacitation. In pre-staining experiments, sperm were stained with MG-560 before capacitation and then incubated to induce capacitation. Acrosome-reacted sperm were assessed after staining with peanut agglutinin FITC (PNA-Lectin FITC). Stained sperm were observed using fluorescence or confocal microscopy.</p><p><strong>Results: </strong>MG-560-stained sperm from the epididymis before capacitation showed four staining patterns: head-midpiece-tail (HMT), head-midpiece (HM), head (H), midpiece (M) positive, or totally negative, with ratios remaining unchanged during capacitation (30.5%, 29%, 11.3%, 3.7%, and 25.5%, respectively). In contrast, all testicular sperm were negative for staining. Pre-stained sperm exhibited an increased number of HM and M patterns over time, whereas the number of HMT-stained sperm decreased. Consistently, spontaneous acrosome-reacted sperm were detected predominantly in HM- or M-stained sperm. After <i>in vitro</i> fertilization (IVF) using pre-stained sperm, zona pellucida-attached sperm were mostly negative for staining. Finally, all sperm detected in the perivitelline space were only negative.</p><p><strong>Conclusions: </strong>Mature sperm membranes stained with MG-560 exhibited heterogeneous and dynamic changes during the capacitation and fertilization process. MG-560 staining identified sperm with the potential to undergo the acrosome reaction, and these MG-560-positive sperm eventually became negative as they penetrated the zona pellucida for fertilization. Thus, the MG-560 staining patterns likely reflect the physiological state and potential of the sperm. These findings provide new insights into sperm heterogeneity and dynamics, and this staining method may also prove useful for assessing sperm quality.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"26784"},"PeriodicalIF":3.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043716","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":"The Formation and Features of Massive Vacuole Induced by Nutrient Deficiency in Human Embryonic Kidney Cells.","authors":"Dakang Sun, Xinye An, Yanli Cheng","doi":"10.31083/FBL26796","DOIUrl":"https://doi.org/10.31083/FBL26796","url":null,"abstract":"<p><strong>Background: </strong>Cellular vacuolization is a commonly observed phenomenon under physiological and pathological conditions. However, the mechanisms underlying vacuole formation remain largely unresolved.</p><p><strong>Methods: </strong>LysoTracker Deep Red probes and Enhanced Green Fluorescent Protein-tagged light chain 3B (LC3B) plasmids were employed to differentiate the types of massive vacuoles. By confocal microscopy, lysosome-like massive vacuoles (LysoTracker Deep Red⁺), autophagosome-like massive vacuoles (LC3B-enhanced green fluorescent protein (EGFP⁺)), and autolysosome-like massive vacuoles (LC3B-EGFP⁺ LysoTracker Deep Red⁺) in starved HEK293T cells were observed.</p><p><strong>Results: </strong>In this study, we demonstrated that nutrient deficiency can induce the formation of massive vacuoles that appear highly electron-lucent in HEK293T cells. Additionally, these massive vacuoles, resulting from nutrient depletion, can originate from various organelles, including small vacuoles, autophagosomes, lysosomes, and autolysosomes. We found that massive vacuoles could form through two primary mechanisms: the accumulation of small vacuoles into larger vacuoles or the fusion of homogeneous or heterogeneous vacuoles. Further analysis revealed that the membranes of massive vacuoles, regardless of origin, were composed of a bilayer membrane structure. As the volume of the massive vacuoles increased, the cytoplasm and nucleus were displaced toward the periphery of the cells, leading to the formation of signet ring-like cells. Interestingly, we provided evidence that complete massive vacuoles or autophagosome-like massive vacuoles can be released and exist independently outside HEK293T cells.</p><p><strong>Conclusions: </strong>Nutrient deprivation induces the formation of heterogeneous, massive vacuoles in human embryonic kidney cells, some of which contribute to the development of signet ring cells, while others lead to extracellular vacuole formation.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"26796"},"PeriodicalIF":3.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043852","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":"Update on the Progress of Musashi-2 in Malignant Tumors.","authors":"Yiting Niu, Tao Zhou, Yanjun Li","doi":"10.31083/FBL24928","DOIUrl":"https://doi.org/10.31083/FBL24928","url":null,"abstract":"<p><p>Since the discovery of the Musashi (MSI) protein, its ability to affect the mitosis of Drosophila progenitor cells has garnered significant interest among scientists. In the following 20 years, it has lived up to expectations. A substantial body of evidence has demonstrated that it is closely related to the development, metastasis, migration, and drug resistance of malignant tumors. In recent years, research on the MSI protein has advanced, and many novel viewpoints and drug resistance attempts have been derived; for example, tumor protein p53 mutations and MSI-binding proteins lead to resistance to protein arginine N-methyltransferase 5-targeted therapy in lymphoma patients. Moreover, the high expression of MSI2 in pancreatic cancer might suppress its development and progression. As a significant member of the MSI family, MSI2 is closely associated with multiple malignant tumors, including hematological disorders, common abdominal tumors, and other tumor types (e.g., glioblastoma, breast cancer). MSI2 is highly expressed in the majority of tumors and is related to a poor disease prognosis. However, its specific expression levels and regulatory mechanisms may differ based on the tumor type. This review summarizes the research progress related to MSI2 in recent years, including its occurrence, migration mechanism, and drug resistance, as well as the prospect of developing tumor immunosuppressants and biomarkers.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"24928"},"PeriodicalIF":3.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043865","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":"The Impact of Selenium on the Physiological Activity of Yeast Cells <i>Saccharomyces cerevisiae</i> ATCC 7090 and <i>Rhodotorula glutinis</i> CCY 20-2-26.","authors":"Wioletta Sęk, Anna M Kot, Marek Kieliszek","doi":"10.31083/FBL26692","DOIUrl":"https://doi.org/10.31083/FBL26692","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the selenium-binding capacity of the biomass of two yeast strains, <i>Saccharomyces cerevisiae</i> American Type Culture Collection (ATCC) 7090 and <i>Rhodotorula glutinis</i> CCY 20-2-26.</p><p><strong>Methods: </strong>The studies carried out methods of bioaccumulation by yeast biomass. Inorganic selenium was added to the culture media as an aqueous solution of Na₂SeO₃ at concentrations ranging from 0 to 40 mg Se⁴⁺/L.</p><p><strong>Results: </strong>The addition of selenium at concentrations >0.5 mg/L significantly reduced biomass yield compared with the control in the case of <i>S. cerevisiae</i>. A significant reduction in the biomass of <i>R. glutinis</i> was observed only at selenium doses >30 mg/L. The study found that for <i>S. cerevisiae</i>, cultivation should occur for 24 h in a medium with an initial selenium concentration of 20 mg/L to achieve the most efficient selenium accumulation by the yeast biomass. Under these conditions, the yeast could accumulate 4.27 mg Se⁴⁺/g. For the red yeast <i>R. glutinis</i>, optimal selenium binding conditions were achieved by cultivating for 48 h in a medium with an initial selenium ion concentration of 40 mg/L. This yeast strain was more resistant to high selenium doses, accumulating 7.53 mg Se⁴⁺/L at the highest tested dose (40 mg Se⁴⁺/L). Selenium supplementation of the medium from 20 mg Se⁴⁺/L and cultivation for 72 h caused significant changes in the morphology of <i>S. cerevisiae</i> cells (e.g., increased surface area compared with the control). Selenium doses of 20-40 mg/L after 48 h of cultivation significantly reduced the surface area compared with the control results for <i>R. glutinis</i> cells.</p><p><strong>Conclusions: </strong>Selenium significantly impacted carotenoid pigment production, with levels decreasing as the selenium concentration in the medium increased. Furthermore, selenium in the tested concentration range increased protein content in the cellular biomass but did not affect intracellular lipid production.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"26692"},"PeriodicalIF":3.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043858","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":"Inhibition of p70 Ribosomal S6K1 Protects the Myocardium against Ischemia/Reperfusion-Induced Necrosis through Downregulation of RIP3.","authors":"Hui Shang, Jinjin Shi, Jun Zhu, Yunfeng Guo, Xiaoyan Wang","doi":"10.31083/FBL26186","DOIUrl":"https://doi.org/10.31083/FBL26186","url":null,"abstract":"<p><strong>Background: </strong>Myocardial ischemia-reperfusion (I/R) injury refers to cell damage that occurs as a consequence of the restoration of blood circulation following reperfusion therapy for cardiovascular diseases, and it is a primary cause of myocardial infarction. The search for nove therapeutic targets in the context of I/R injury is currently a highly active area of research. p70 ribosomal S6 kinase (S6K1) plays an important role in I/R induced necrosis, although the specific mechanisms remain unclear.</p><p><strong>Objective: </strong>This study aims to explore the effects of inhibiting S6K1 on myocardial I/R injury and its potential mechanisms.</p><p><strong>Methods: </strong>A rat myocardial I/R model was created and treated with the S6K1-specific inhibitor PF-4708671. Hematoxylin-eosin (H&E) staining was applied to evaluate the pathological changes in cardiac tissues. 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to measure the area of myocardial infarction (MI). Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum rate of increase in left ventricular pressure (+dp/dtmax), and the maximum rate of the decrease in left ventricular pressure (-dp/dtmax) were measured using ultrasonic echocardiography. The expression levels of cardiac troponin-1 (cTn-1), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), and aspartate aminotransferase (AST) were determined by enzyme-linked immunosorbent assay (ELISA). Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and propidium iodide (PI) staining were used to examine the apoptosis and necrosis of myocardial tissues. The expressions of apoptotic-related proteins, and key molecules of necrosis were detected by western blot. The relationship between S6K1 and receptor-interacting protein kinase 3 (RIP3) was analyzed by immunoprecipitation.</p><p><strong>Results: </strong>Inhibition of S6K1 reduces I/R-induced myocardial tissue damage, improves myocardial function, and inhibits myocardial tissue necrosis (<i>p</i> < 0.05). In addition, RIP3 is a direct target of S6K1, and activation of RIP3 blocked the protective effect of the S6K1 inhibitor PF-4708671 against myocardial I/R injury (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>Inhibition of S6K1 protects against myocardial I/R injury by down-regulating RIP3, suggesting that targeting S6K1 may offer a novel approach for intervention in myocardial I/R injury.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"26186"},"PeriodicalIF":3.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061183","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":"The Role of Sulfatides in Liver Health and Disease.","authors":"Lin Chen, Montserrat Elizalde, Gloria Alvarez-Sola","doi":"10.31083/FBL25077","DOIUrl":"https://doi.org/10.31083/FBL25077","url":null,"abstract":"<p><p>Sulfatides or 3-O-sulfogalactosylceramide are negatively charged sulfated glycosphingolipids abundant in the brain and kidneys and play crucial roles in nerve impulse conduction and urinary pH regulation. Sulfatides are present in the liver, specifically in the biliary tract. Sulfatides are self-lipid antigens presented by cholangiocytes to activate cluster of differentiation 1d (CD1d)-restricted type II natural killer T (NKT) cells. These cells are involved in alcohol-related liver disease (ArLD) and ischemic liver injury and exert anti-inflammatory effects by regulating the activity of pro-inflammatory type I NKT cells. Loss of sulfatides has been implicated in the chronic inflammatory disorder of the liver known as primary sclerosing cholangitis (PSC); bile ducts deficient in sulfatides increase their permeability, resulting in the spread of bile into the liver parenchyma. Previous studies have shown elevated levels of sulfatides in hepatocellular carcinoma (HCC), where sulfatides could act as adhesive molecules that contribute to cancer metastasis. We have recently demonstrated how loss of function of GAL3ST1, a limiting enzyme involved in sulfatide synthesis, reduces tumorigenic capacity in cholangiocarcinoma (CCA) cells. The biological function of sulfatides in the liver is still unclear; however, this review aims to summarize the existing findings on the topic.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"25077"},"PeriodicalIF":3.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043825","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":"Therapeutic Effects of GDF6-Overexpressing Mesenchymal Stem Cells through Upregulation of the GDF15/SIRT1 Axis in Age-Related Hearing Loss.","authors":"Jiali Liu, Haisen Peng, Yuehui Liu, Chunhua Li, Wen Xie","doi":"10.31083/FBL26179","DOIUrl":"https://doi.org/10.31083/FBL26179","url":null,"abstract":"<p><strong>Background: </strong>It has been reported the therapeutic effects of mesenchymal stem cells (MSCs) on hearing loss. This study explored the therapeutic effects of growth differentiation factor 6 (GDF6) overexpression-induced MSCs (MSCs-GDF6) on age-related hearing loss (ARHL) and its underlying mechanisms.</p><p><strong>Methods: </strong>Reverse transcription-quantitative PCR and western blotting were used to evaluate gene expression. Flow cytometry and immunofluorescence assays were performed for the detection of apoptosis and autophagy, respectively. Hearing function and loss of outer hair cells (HCs) in ARHL rats were measured using the auditory brainstem response and cochlear silver nitrate staining, respectively. MSC proliferation was evaluated with the Cell Counting Kit-8 assay.</p><p><strong>Results: </strong>Growth differentiation factor 15 (GDF15) and sirtuin 1 (SIRT1) expression was significantly decreased in hydrogen peroxide (H₂O₂)-induced House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and the cochlea of ARHL rats. Elevated apoptosis and blocked autophagic flux were uncovered in H₂O₂-induced HEI-OC1 cells and ARHL rats. GDF15 overexpression inhibited apoptosis and restored autophagic flux <i>in vitro</i> and <i>in vivo</i>. Meanwhile, GDF15 positively regulated SIRT1 protein expression. MSCs-GDF6 not only upregulated GDF15 and SIRT1 expression but also suppressed apoptosis and restored autophagic flux to reduce loss of HCs and hearing loss in ARHL rats.</p><p><strong>Conclusions: </strong>MSCs-GDF6 prevented loss of HCs to relieve ARHL by inhibiting apoptosis and restoring autophagic flux, likely in association with upregulation of the GDF15/SIRT1 axis.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"26179"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043827","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":"Plant Colonization by Biocontrol Bacteria and Improved Plant Health: A Review.","authors":"Roohallah Saberi Riseh, Fariba Fathi, Mozhgan Gholizadeh Vazvani, Mika Tapio Tarkka","doi":"10.31083/FBL23223","DOIUrl":"https://doi.org/10.31083/FBL23223","url":null,"abstract":"<p><p>The use of biological control agents is one of the best strategies available to combat the plant diseases in an ecofriendly manner. Biocontrol bacteria capable of providing beneficial effect in crop plant growth and health, have been developed for several decades. It highlights the need for a deeper understanding of the colonization mechanisms employed by biocontrol bacteria to enhance their efficacy in plant pathogen control. The present review deals with the in-depth understanding of steps involved in host colonization by biocontrol bacteria. The colonization process starts from the root zone, where biocontrol bacteria establish initial interactions with the plant's root system. Moving beyond the roots, biocontrol bacteria migrate and colonize other plant organs, including stems, leaves, and even flowers. Also, the present review attempts to explore the mechanisms facilitating bacterial movement within the plant such as migrating through interconnected spaces such as vessels or in the apoplast, and applying quorum sensing or extracellular enzymes during colonization and what is needed to establish a long-term association within a plant. The impacts on microbial community dynamics, nutrient cycling, and overall plant health are discussed, emphasizing the intricate relationships between biocontrol bacteria and the plant's microbiome and the benefits to the plant's above-ground parts, the biocontrol 40 bacteria confer. By unraveling these mechanisms, researchers can develop targeted strategies for enhancing the colonization efficiency and overall effectiveness of biocontrol bacteria, leading to more sustainability and resilience.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"23223"},"PeriodicalIF":3.3,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043840","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":"Ignoring Gender-Based Immunometabolic Reprograming, a Risky Business in Immune-Based Precision Medicine.","authors":"Vijay Kumar","doi":"10.31083/FBL27118","DOIUrl":"https://doi.org/10.31083/FBL27118","url":null,"abstract":"<p><p>Immunology advances have increased our understanding of autoimmune, auto-inflammatory, immunodeficiency, infectious, and other immune-mediated inflammatory diseases (IMIDs). Furthermore, evidence is growing for the immune involvement in aging, metabolic and neurodegenerative diseases, and different cancers. However, further research has indicated sex/gender-based immune differences, which further increase higher incidences of various autoimmune diseases (AIDs), such as systemic lupus erythematosus (SLE), myasthenia gravis, and rheumatoid arthritis (RA) in females. On the other hand, reproductive-age females also show a more potent immune response against infections and vaccines than their age-matched males-furthermore, some immune-based therapies, including immune checkpoint inhibitors (ICIs), show gender-based efficacy and adverse events. Metabolic demands are different in males and females. Immune cell function and polarization are also governed by their metabolic reprogramming, called immunometabolism and immunometabolic reprogramming (IR). Therefore, sex/gender-associated immune differences and their involvement in immune-mediated diseases and immune-based therapeutics indicate the demand for gender-based IR studies to increase the efficacy of immune-based precision medicine.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"27118"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043744","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":"HIF-1α and VEGF Immunophenotypes as Potential Biomarkers in the Prognosis and Evaluation of Treatment Efficacy of Atherosclerosis: A Systematic Review of the Literature.","authors":"Dimitra P Vageli, Panagiotis G Doukas, Dimitrios Georgiou, Michailangelos P Prokopiou, Nefeli E Ladaki, Androniki Papadopoulou, Sotirios G Doukas, Konstantina Zacharouli, Konstantinos P Makaritsis, Maria Ioannou","doi":"10.31083/FBL27004","DOIUrl":"https://doi.org/10.31083/FBL27004","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hypoxia-inducible factor 1 alpha (HIF-1α) and its related vascular endothelial growth factor (VEGF) may play a significant role in atherosclerosis and their targeting is a strategic approach that may affect multiple pathways influencing disease progression. This study aimed to perform a systematic review to reveal current evidence on the role of HIF-1α and VEGF immunophenotypes with other prognostic markers as potential biomarkers of atherosclerosis prognosis and treatment efficacy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We performed a systematic review of the current literature to explore the role of HIF-1α and VEGF protein expression along with the relation to the prognosis and therapeutic strategies of atherosclerosis. We used the terms {\"Atherosclerosis\" [OR] \"Atheroma\" [OR] \"atheromatous plaque\" [OR] \"plaque atherosclerotic\"} [AND] {\"HIF-1α\"} [AND] {\"VEGF\"} from 2009 up to May 2024 and the Medline/Embase/PubMed database. We used methodological approaches to assess unbiased data [ROBIS (Risk of Bias in Systematic) tool]. We used study eligibility criteria, and data were collected and evaluated from original articles by two independent teams, judged by an independent reviewer, and reported by PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We included 34 original studies investigating 650 human specimens, 21 different cell lines, and 9 animal models. Increased HIF-1α in vascular smooth muscle cells, macrophages, or endothelial cells, under hypoxia, chronic loss of nitric oxide (NO), or reduced micro ribonucleic acid (miRNA)-17 and miR-20, is associated with the upregulation of pro-inflammatory molecules, such as interleukin-1 beta (IL-1β) or tumor necrosis factor-alpha (TNF-α), increased migration inhibitory factor of macrophages, glycolytic flux, lipid accumulation, necroptosis via miR-383, and adverse effects in atherosclerosis and plaque vulnerability. However, increased HIF-1α in lymphocytes is associated with decreased interferon-gamma (IFN-γ) and a favorable prognosis. Increased VEGF in a coronary artery, activated macrophages, or chronic exposure to methamphetamine is associated with elevated levels of serum inflammatory cells (interleukin-18; IL18), p38 mitogen-activated protein kinase (MAPK) phosphorylation, lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF), and signal transducer and activator of transcription 6 isoform B (STAT6B) overexpression, leading to atherosclerosis progression and plaque break. However, VEGF overexpression in serum is marginally associated with an elevated risk for atherosclerosis. In contrast, stable overexpression of VEGF in macrophages correlates with reduced hyperplasia after arterial injury, reduced foam cell formation, and attenuation of atherosclerosis progression. HIF-1α/VEGF immunophenotypes reflect atherosclerosis treatment efficacy using, among others, HIF-inhibitors, statins, polyphenols, ","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 1","pages":"27004"},"PeriodicalIF":3.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043719","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}