Journal of Biological Engineering最新文献

{"title":"Codeine 3-O-demethylase catalyzed biotransformation of morphinan alkaloids in Escherichia coli: site directed mutagenesis of terminal residues improves enzyme expression, stability and biotransformation yield.","authors":"Garrick W K Spencer, Xu Li, Kenny W L Lam, George Mutch, Fiona H Fry, Sally L Gras","doi":"10.1186/s13036-025-00477-0","DOIUrl":"10.1186/s13036-025-00477-0","url":null,"abstract":"<p><p>The cultivation of opium poppy is the only commercially viable source of most morphinan alkaloids. Bioproduction of morphinan alkaloids in recombinant whole-cell systems provides a promising alternate source of these valuable compounds. The enzyme codeine 3-O-demethylase can transform morphinan alkaloids by O-demethylation and has been applied in single step biotransformation reactions or as part of larger biosynthetic cascade, however, the productivity for these reactions remains low and suboptimal enzyme properties could be improved. This mutagenesis study targeted non-conserved N-and C-terminal residues, which were replaced with the equivalent residues from enzyme thebaine 6-O-demethylase. Whole cell biotransformation performance was significantly improved in Escherichia coli expressing codeine 3-O-demethylase mutants, with a ~ 2.8-fold increase in the production of oripavine from thebaine and ~ 1.3-fold increase in the production of morphine from codeine. Statistical analysis of biotransformation yield, enzyme expression and stability, predicted using changes in Gibbs free energy (ΔΔG) with deep-learning-based model DDmut, suggested that altered enzyme stability and/or expression of soluble protein may contribute to the observed improvements in biotransformation. This approach could be beneficial for screening future codeine 3-O-demethylase mutations and for other enzymes.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"9"},"PeriodicalIF":5.7,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioprocess exploitation of microaerobic auto-induction using the example of rhamnolipid biosynthesis in Pseudomonas putida KT2440.","authors":"Jakob Grether, Holger Dittmann, Leon Willems, Tabea Schmiegelt, Elvio Henrique Benatto Perino, Philipp Hubel, Lars Lilge, Rudolf Hausmann","doi":"10.1186/s13036-025-00478-z","DOIUrl":"10.1186/s13036-025-00478-z","url":null,"abstract":"<p><strong>Background: </strong>In biomanufacturing of surface-active agents, such as rhamnolipids, excessive foaming is a significant obstacle for the development of high-performing bioprocesses. The exploitation of the inherent tolerance of Pseudomonas putida KT2440, an obligate aerobic bacterium, to microaerobic conditions has received little attention so far. Here low-oxygen inducible promoters were characterized in biosensor strains and exploited for process control under reduction of foam formation by low aeration and stirring rates during biosynthesis of rhamnolipids.</p><p><strong>Results: </strong>In this study, homologous promoters of P. putida inducible under oxygen limitation were identified by non-targeted proteomic analyses and characterized by fluorometric methods. Proteomics indicated a remodeling of the respiratory chain and the regulation of stress-related proteins under oxygen limitation. Of the three promoters tested in fluorescent biosensor assays, the promoter of the oxygen-sensitive cbb3-type cytochrome c oxidase gene showed high oxygen-dependent controllability. It was used to control the gene expression of a heterologous di-rhamnolipid synthesis operon in an auto-inducing microaerobic two-phase bioprocess. By limiting the oxygen supply via low aeration and stirring rates, the bioprocess was clearly divided into a growth and a production phase, and sources of foam formation were reduced. Accordingly, rhamnolipid synthesis did not have to be controlled externally, as the oxygen-sensitive promoter was autonomously activated as soon as the oxygen level reached microaerobic conditions. A critical threshold of about 20% oxygen saturation was determined.</p><p><strong>Conclusions: </strong>Utilizing the inherent tolerance of P. putida to microaerobic conditions in combination with the application of homologous, low-oxygen inducible promoters is a novel and efficient strategy to control bioprocesses. Fermentation under microaerobic conditions enabled the induction of rhamnolipid production by low oxygen levels, while foam formation was limited by low aeration and stirring rates.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"8"},"PeriodicalIF":5.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BCL-2 overexpression exosomes promote the proliferation and migration of mesenchymal stem cells in hypoxic environment for skin injury in rats.","authors":"Ying Wang, Guang Li, Guofeng Li, Yutao Pan, Zhongmin Liu","doi":"10.1186/s13036-024-00471-y","DOIUrl":"10.1186/s13036-024-00471-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The direction of this study was to detect and analyze the specific mechanism of anti-apoptosis in mesenchymal stem cells (MSCs) cells caused by high expression of BCL2.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Bioinformatics was completed in Link omics. GO analysis and KEGG analysis were carried out, and the grope tool of Link omics database was used to evaluate PPI information and other core path analysis information. The cultured cells were divided into MSC + normoxic group (MSCs were cultured in conventional medium, including 10% depleted serum of fetal bovine exosomes, 37 °C, 5% CO&lt;sub&gt;2&lt;/sub&gt; and 95% air) and Exo-BCL-2 + MSC + normoxic group (a certain concentration of purified BCL-2 exosomes was co-cultured with MSC in conventional medium, 37 °C, 5% CO&lt;sub&gt;2&lt;/sub&gt; and 95% air), Exo-BCL-2 + MSC + hypoxia group (a certain concentration of purified BCL-2 exosomes and MSC were co-cultured in hypoxia medium at 37 °C, 80% CO&lt;sub&gt;2&lt;/sub&gt; and 20% air), MSC + hypoxia group (MSCs were cultured in hypoxia medium with 10% depleted serum of fetal bovine exosomes, 37 °C, 80% CO&lt;sub&gt;2&lt;/sub&gt; and 20% air), exo WT + MSC + normoxic group (co-cultured with MSC in conventional medium at 37 °C, 5% CO&lt;sub&gt;2&lt;/sub&gt; and 95% air) and exoWT + MSC + hypoxic group (co-cultured with MSC in hypoxic medium at 37 °C, 80% CO&lt;sub&gt;2&lt;/sub&gt; and 20%). Cell proliferation ability was monitored by cell proliferation test. Cell migration test was used to check the migration capacity of MSCs. The expressions of apoptosis-related proteins BCL-2, caspase3 and caspase9, Runx2, ALP and PPAR-γ were analyzed by western blot. Tissue damage was scored by H&E and Ma Song trichrome staining. Masson staining was used to evaluate the collagen volume fraction of the wound. The expressions of KRT14, α-SMA, CD31 and PCNA in rat trauma tissues were analyzed by immunofluorescence staining. The horizontal of apoptosis-related proteins in skin lesions was checked by Western blot. The horizontal of inflammatory factors TNF-α and IL-6 in traumatic tissue of rats were detected by ELISA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;From KEGG's results, we can see that BCL2-2 was closely related to base excision and repair, cell cycle, steroid biosynthesis and other pathways. When cultured for 48h and 72h, the proliferation ability and migration number of MSCs in MSC + hypoxia group were lower than MSC + normoxic group, but the expressions of caspase3 and caspase9 were higher. The proliferation ability and migration number of MSCs in Exo-BCL-2 + MSC + hypoxia group and MSC + hypoxia group were lower than those in Exo-BCL-2 + MSC + normoxic group and MSC + normoxic group, and the horizontal of caspase3 and caspase9 were lower. Exo-BCL-2 + MSC + normoxic group increased the proliferation capacity and migration number of MSCs, but decreased the expression of caspase3 and caspase9. Compared with Exo-BCL-2 + MSC + normoxia and Exo-BCL-2 + MSC + normoxia, the proliferation ability and migration quantity o","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"7"},"PeriodicalIF":5.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering Yarrowia lipolytica for the production of β-carotene by carbon and redox rebalancing.","authors":"Hojun Lee, Jinwoo Song, Sang Woo Seo","doi":"10.1186/s13036-025-00476-1","DOIUrl":"10.1186/s13036-025-00476-1","url":null,"abstract":"<p><strong>Background: </strong>β-Carotene is a natural product that has garnered significant commercial interest. Considerable efforts have been made to meet such demand through the metabolic engineering of microorganisms, yet there is still potential for improvement. In this study, engineering approaches including carbon and redox rebalancing were used to maximize β-carotene production in Yarrowia lipolytica.</p><p><strong>Results: </strong>The initial production level was increased by iterative overexpression of pathway genes with lycopene inhibition removal. For further improvement, two approaches that redirect the central carbon pathway were evaluated to increase NADPH regeneration and reduce ATP expenditure. Pushing flux through the pentose phosphate pathway and introducing NADP⁺-dependent glyceraldehyde-3-phosphate dehydrogenase were found to be more effective than the phosphoketolase-phosphotransacetylase (PK-PTA) pathway. Furthermore, flux to the lipid biosynthesis pathway was moderately increased to better accommodate the increased β-carotene pool, resulting in the production level of 809.2 mg/L.</p><p><strong>Conclusions: </strong>The Y. lipolytica-based β-carotene production chassis was successfully developed through iterative overexpression of multiple pathways, central carbon pathway engineering and lipid pathway flux adjustment. The approach presented here provides insights into future endeavors to improve microbial terpenoid production capability.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"6"},"PeriodicalIF":5.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scale-up of CHO cell cultures: from 96-well-microtiter plates to stirred tank reactors across three orders of magnitude.","authors":"Anne Neuss, Thomas Steimann, Jacinta Sofia Tomas Borges, Robert Dinger, Jørgen Barsett Magnus","doi":"10.1186/s13036-024-00475-8","DOIUrl":"10.1186/s13036-024-00475-8","url":null,"abstract":"<p><strong>Background: </strong>For process development in mammalian cell cultivations, scale-up approaches are essential. A lot of studies concern the scale transfer between different-sized stirred tank reactors. However, process development usually starts in even smaller cultivation vessels like microtiter plates or shake flasks. A scale-up from those small shaken devices to a stirred tank reactor is barely stated in literature for mammalian cells. Thus, this study aims to address data-driven scale-up for CHO DP12 cells. The oxygen transfer rate is used as a database.</p><p><strong>Results: </strong>The cultivation conditions in microtiter plates and shake flasks are comparable when choosing the maximum oxygen transfer capacity as a scale-up parameter. The minimum cultivation volume was reduced to 400 µL in round and square 96-deep-well microtiter plates. Using a scale-up based on the maximum oxygen transfer capacity to a stirred tank reactor led to conditions with excessive hydromechanical stress. However, cultivation conditions could be reproduced in a stirred tank reactor by utilizing the volumetric power input as a scale-up parameter. Key metabolites behaved the same in all three scales and the final antibody titer was equal.</p><p><strong>Conclusion: </strong>This study presents a successful replication of cultivation results for mammalian cells in microtiter plates, shake flasks and stirred tank reactors. The working volumes ranged from 0.4 to 50 and 600 mL. It offers the opportunity to adapt the method to other, more sensitive mammalian cells and to perform cost- and time-effective experiments in high-throughput.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"5"},"PeriodicalIF":5.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stabilizing milk-derived extracellular vesicles (mEVs) through lyophilization: a novel trehalose and tryptophan formulation for maintaining structure and Bioactivity during long-term storage.","authors":"Alan B Dogan, Spencer R Marsh, Rachel J Tschetter, Claire E Beard, Md R Amin, L Jane Jourdan, Robert G Gourdie","doi":"10.1186/s13036-024-00470-z","DOIUrl":"10.1186/s13036-024-00470-z","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are widely investigated for their implications in cell-cell signaling, immune modulation, disease pathogenesis, cancer, regenerative medicine, and as a potential drug delivery vector. However, maintaining integrity and bioactivity of EVs between Good Manufacturing Practice separation/filtration and end-user application remains a consistent bottleneck towards commercialization. Milk-derived extracellular vesicles (mEVs), separated from bovine milk, could provide a relatively low-cost, scalable platform for large-scale mEV production; however, the reliance on cold supply chain for storage remains a logistical and financial burden for biologics that are unstable at room temperature. Herein, we aim to characterize and engineer a freeze-dried, mEV formulation that can be stored at room temperature without sacrificing structure/bioactivity and can be reconstituted before delivery. In addition to undertaking established mEV assays of structure and function on our preparations, we introduce a novel, efficient, high throughput assay of mEV bioactivity based on Electric Cell Substrate Impedance Sensing (ECIS) in Human dermal fibroblast monolayers. By adding appropriate excipients, such as trehalose and tryptophan, we describe a protective formulation that preserves mEV bioactivity during long-term, room temperature storage. Our identification of the efficacy of tryptophan as a novel additive to mEV lyophilization solutions could represent a significant advancement in stabilizing small extracellular vesicles outside of cold storage conditions.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"4"},"PeriodicalIF":5.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lithium-doped calcium silicate cement regulates the immune microenvironment and promotes M2 macrophage polarization for enhancing bone regeneration.","authors":"Yen-Hong Lin, Cheng-Yu Chen, Kun-Hao Chen, Ting-You Kuo, Tsung-Li Lin, Ming-You Shie","doi":"10.1186/s13036-024-00467-8","DOIUrl":"https://doi.org/10.1186/s13036-024-00467-8","url":null,"abstract":"<p><p>Bone defects present a significant challenge in orthopedics and trauma surgery, necessitating innovative approaches to stimulate effective bone regeneration. This study investigated the potential of lithium-doped calcium silicate (LiCS) cement to enhance bone regeneration and modulate the immune microenvironment to promote tissue repair. We synthesized a LiCS ceramic powder and performed comprehensive analyses of its physicochemical properties, including phase composition, morphology, setting time, and mechanical strength. The results demonstrated that the incorporation of lithium into calcium silicate significantly increased the diametral tensile strength (DTS) and facilitated hydroxyapatite formation compared with undoped calcium silicate. In vitro assays revealed that the LiCS cement enhanced the proliferation, adhesion, and spread of Wharton's jelly mesenchymal stem cells (WJMSCs). Additionally, Li-CS cement exhibited remarkable immunomodulatory properties by reducing pro-inflammatory cytokines and increasing anti-inflammatory cytokines, promoting the polarization of macrophages towards the M2 phenotype. The presence of Li in the cement also significantly improved the osteogenic differentiation of WJMSCs, as evidenced by elevated levels of alkaline phosphatase and osteocalcin expression. These findings underscore the dual functional capabilities of the LiCS cement in enhancing osteogenesis and modulating the immune environment, making it a promising material for bone tissue engineering and regeneration.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"3"},"PeriodicalIF":5.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesizing hybrid copper phosphate (Cu₃(PO₄)₂) nanoflowers using Cu⁺² and shed snakeskin: antioxidant, antibacterial, anticancer, guaiacol, anionic, and cationic dye degradation properties.","authors":"Cagri Caglar Sinmez, Fatih Doğan Koca","doi":"10.1186/s13036-024-00464-x","DOIUrl":"https://doi.org/10.1186/s13036-024-00464-x","url":null,"abstract":"<p><strong>Background: </strong>Synthesis of organic@inorganic hNFs is achieved by the coordination of organic compounds containing amine, amide, and diol groups with bivalent metals. The use of bio-extracts containing these functional groups instead of expensive organic inputs such as DNA, enzymes, and protein creates advantages in terms of cost and applicability. In this study, the application potentials (antioxidant, antibacterial, anticancer, guaiacol, anionic, and cationic dye degradation) of hybrid (organic@inorganic) nanoflowers (hNFs) synthesized with Cu⁺² and snakeskin (SSS) were proposed.</p><p><strong>Results: </strong>Morphology, presence, and composition of elements of Cu and SSS-coordinated hNFs (Cu@SSS hNFs) were shown through FE-SEM-EDX spectroscopy. According to FE-SEM findings, hNFs synthesized with 0.5 ml and 1 ml extract have diameters of 12.81 and 3 µm, respectively. Diffraction peaks of hNFs determined by XRD were consistent with JCPDS Card 00-022 -0548. Cu@SSS NFs showed antioxidant properties depending on time through DPPH scavenging behavior (ability (R²: 0.5612, IC₅₀: 2.07 mg/ml). Cu@SSS hNFs synthesized coordination of SSS and Cu degraded (75%) methylene blue at the highest pH 9 condition. However, hNFs highest degraded (68%) brilliant blue in an acidic PBS medium. hNFs oxidized guaiacol depending on exposure time. Cu@SSS hNFs demonstrated antibacterial properties towards Gram (-/ +) pathogen strains (MIC: 60 µg/ml). The catalytic and antimicrobial properties of hNFs were mentioned by the Fenton reaction. The cytotoxicity of Cu@SSS hNFs on the lung carcinoma (A549) cell line was shown to be concentration-dependent by the MTT test assay (IC₅₀: 56.4 µg/ml).</p><p><strong>Conclusion: </strong>As a result, Cu-based hNFs synthesized by using an organic waste (SSS) might be improved for environmental and biomedical applications.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"1"},"PeriodicalIF":5.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced metabolic Engineering strategies for the sustainable production of free fatty acids and their derivatives using yeast.","authors":"Tisa Rani Saha, Nam Kyu Kang, Eun Yeol Lee","doi":"10.1186/s13036-024-00473-w","DOIUrl":"10.1186/s13036-024-00473-w","url":null,"abstract":"<p><p>The biological production of lipids presents a sustainable method for generating fuels and chemicals. Recognized as safe and enhanced by advanced synthetic biology and metabolic engineering tools, yeasts are becoming versatile hosts for industrial applications. However, lipids accumulate predominantly as triacylglycerides in yeasts, which are suboptimal for industrial uses. Thus, there have been efforts to directly produce free fatty acids and their derivatives in yeast, such as fatty alcohols, fatty aldehydes, and fatty acid ethyl esters. This review offers a comprehensive overview of yeast metabolic engineering strategies to produce free fatty acids and their derivatives. This study also explores current challenges and future perspectives for sustainable industrial lipid production, particularly focusing on engineering strategies that enable yeast to utilize alternative carbon sources such as CO₂, methanol, and acetate, moving beyond traditional sugars. This review will guide further advancements in employing yeasts for environmentally friendly and economically viable lipid production technologies.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"18 1","pages":"73"},"PeriodicalIF":5.7,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutathione peroxidase 4 overexpression induces anomalous subdiffusion and impairs glioblastoma cell growth.","authors":"Nahom Teferi, Akalanka Ekanayake, Stephenson B Owusu, Thomas O Moninger, Jann N Sarkaria, Alexei V Tivanski, Michael S Petronek","doi":"10.1186/s13036-024-00472-x","DOIUrl":"10.1186/s13036-024-00472-x","url":null,"abstract":"<p><p>Glioblastoma tumors are the most common and aggressive adult central nervous system malignancy. Nearly all patients experience disease progression, which significantly contributes to disease mortality. Recently, it has been suggested that recurrent tumors may be characterized by a ferroptosis-prone phenotype with a significant decrease in glutathione peroxidase 4 (GPx4) expression. This led to the hypothesis that GPx4 expression negatively influences GBM cell growth. This study utilizes a doxycycline inducible GPx4 overexpression model to test this hypothesis. Consistently, the overexpression of GPx4 significantly impairs cell growth and colony formation while also causing an accumulation of cells in G1/G0 phase of the cell cycle. From a biophysical perspective, GPx4 overexpressing cells have significantly greater surface area, increased Young's modulus, and experience anomalous sub-diffusion as opposed to normal diffusion associated with Brownian motion. Moreover, analysis of patient derived GBM cells reveal that cell growth rates, plating efficiency, and Young's modulus are all inversely proportional to GPx4 expression. Therefore, GPx4 appears to be a biophysical regulator of GBM cell growth that warrants further mechanistic investigation in its role in GBM progression.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"18 1","pages":"72"},"PeriodicalIF":5.7,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}