Molecular Biotechnology最新文献

{"title":"Effect of Different Karyophilic Peptides on Physical Characteristics and In Vitro Transfection Efficiency of Chitosan-Plasmid Nanoparticles as Nonviral Gene Delivery Systems.","authors":"María Eugenia Aranda-Barradas, Héctor Eduardo Coronado-Contreras, Yareli Lizbeth Aguilar-Castañeda, Karen Donají Olivo-Escalante, Francisco Rodolfo González-Díaz, Carlos Gerardo García-Tovar, Samuel Álvarez-Almazán, Susana Patricia Miranda-Castro, Alicia Del Real-López, Abraham Méndez-Albores","doi":"10.1007/s12033-024-01087-9","DOIUrl":"10.1007/s12033-024-01087-9","url":null,"abstract":"<p><p>A strategy to increase the transfection efficiency of chitosan-based nanoparticles for gene therapy is by adding nuclear localization signals through karyophilic peptides. Here, the effect of the length and sequence of these peptides and their interaction with different plasmids on the physical characteristics and biological functionality of nanoparticles is reported. The karyophilic peptides (P1 or P2) were used to assemble nanoparticles by complex coacervation with pEGFP-N1, pQBI25 or pSelect-Zeo-HSV1-tk plasmids, and chitosan. Size, polydispersity index, zeta potential, and morphology, as well as in vitro nucleus internalization and transfection capability of nanoparticles were determined. The P2 nanoparticles resulted smaller compared to the ones without peptides or P1 for the three plasmids. In general, the addition of either P1 or P2 did not have a significant impact on the polydispersity index and the zeta potential. P1 and P2 nanoparticles were localized in the nucleus after 30 min of exposure to HeLa cells. Nevertheless, the presence of P2 in pEGFP-N1 and pQBI25 nanoparticles raised their capability to transfect and express the green fluorescent protein. Thus, karyophilic peptides are an efficient tool for the optimization of nonviral vectors for gene delivery; however, the sequence and length of peptides have an impact on characteristics and functionality of nanoparticles.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"723-733"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HELLS Knockdown Inhibits the Malignant Progression of Lung Adenocarcinoma Via Blocking Akt/CREB Pathway by Downregulating KIF11.","authors":"Gang Yang, Jinsong Fu, Jiawei Wang, Mei Ding","doi":"10.1007/s12033-024-01066-0","DOIUrl":"10.1007/s12033-024-01066-0","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is a malignant tumor with the characteristics of progressive advancement and high mortality rate worldwide. We aimed to explore the role and mechanism of helicase Lymphoid-Specific (HELLS) in LUAD. Bioinformatics databases were applied to predict HELLS and kinesin family member (KIF)11 expression in LUAD tissues. The expressions of HELLS and KIF11 before and after HELLS knockdown were detected by RT-qPCR and western blot. After HELLS was knocked down, the proliferative, migratory, and invasive capabilities of A549 cells were evaluated. Cell apoptotic level was assessed using TUNEL. Western blot was employed to evaluate the expressions of Akt/CREB pathway-related proteins. The interaction between HELLS and KIF11 was analyzed using bioinformatics databases, and testified by Co-IP assay. Results revealed that HELLS and KIF11 expressions were significantly upregulated in LUAD cells and tissues. High HELLS and KIF11 expression was correlated with the poor prognosis of patients with LUAD. Additionally, HELLS knockdown suppressed the capabilities of LUAD cells to proliferate, migrate, and invade whereas promoted the cell apoptotic level. Moreover, HELLS could interact with KIF11 and had positive correlation with KIF11. Furthermore, KIF11 overexpression partially counteracted the impacts of HELLS knockdown on cell proliferative, migratory, invasive capabilities, and apoptotic level in LUAD cells. Besides, Akt/CREB pathway was blocked by HELLS silencing, which was restored by KIF11 overexpression. Collectively, HELLS knockdown blocked Akt/CREB pathway by downregulating KIF11 expression, thereby inhibiting LUAD cell proliferation, invasion, migration, and promoting apoptosis.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"548-561"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120120","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":"From Efficiency to Yield: Exploring Recent Advances in CHO Cell Line Development for Monoclonal Antibodies.","authors":"Sarmishta Majumdar, Ranjeet Desai, Aakarsh Hans, Prajakta Dandekar, Ratnesh Jain","doi":"10.1007/s12033-024-01060-6","DOIUrl":"10.1007/s12033-024-01060-6","url":null,"abstract":"<p><p>The increasing demand for biosimilar monoclonal antibodies (mAbs) has prompted the development of stable high-producing cell lines while simultaneously decreasing the time required for screening. Existing platforms have proven inefficient, resulting in inconsistencies in yields, growth characteristics, and quality features in the final mAb products. Selecting a suitable expression host, designing an effective gene expression system, developing a streamlined cell line generation approach, optimizing culture conditions, and defining scaling-up and purification strategies are all critical steps in the production of recombinant proteins, particularly monoclonal antibodies, in mammalian cells. As a result, an active area of study is dedicated to expression and optimizing recombinant protein production. This review explores recent breakthroughs and approaches targeted at accelerating cell line development to attain efficiency and consistency in the synthesis of therapeutic proteins, specifically monoclonal antibodies. The primary goal is to bridge the gap between rising demand and consistent, high-quality mAb production, thereby benefiting the healthcare and pharmaceutical industries.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"369-392"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139741454","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":"Endoplasmic Reticulum Stress Promotes Neuronal Damage in Neonatal Hypoxic-Ischemic Brain Damage by Inducing Ferroptosis.","authors":"Yongjia Ji, Huili Liu, Fang Niu, Bo Kang, Xiu Luo, Hua Yang, Zhen Tian, Juan Yang","doi":"10.1007/s12033-024-01095-9","DOIUrl":"10.1007/s12033-024-01095-9","url":null,"abstract":"<p><p>Hypoxic-ischemic brain damage (HIBD) poses a significant risk of neurological damage in newborns. This study investigates the impact of endoplasmic reticulum stress (ERS) on neuronal damage in neonatal HIBD and its underlying mechanisms. HIBD neonatal rat model was constructed and pre-treated with 4-phenylbutiric acid (4-PBA). Nissl and TUNEL staining were utilised to assess neuronal damage and apoptosis in rat brains. HIBD cell model was established by inducing oxygen-glucose deprivation (OGD) in rat H19-7 neurons, which were then pre-treated with Thapsigargin (TG), Ferrostatin-1 (Fer-1), or both. Cell viability and apoptosis of H19-7 neurons were analysed using cell counting kit-8 assay and TUNEL staining. GRP78-PERK-CHOP pathway activity and glutathione peroxidase-4 (GPX4) expression in rat brains and H19-7 neurons were assessed using Western blot. Ferroptosis-related indicators, including glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and iron content, were measured using commercial kits in both rat brains and H19-7 neurons. GRP78-PERK-CHOP pathway was overactivated in HIBD neonatal rats' brains, which was mitigated by 4-PBA treatment. 4-PBA treatment demonstrated a reduction in neuronal damage and apoptosis in HIBD-affected neonatal rat brains. Furthermore, it attenuated ferroptosis in rats by increasing GPX4, GSH and SOD while decreasing MDA and iron content. In the OGD-induced H19-7 neurons, Fer-1 treatment counteracted the suppressive effects of TG on viability, the exacerbation of apoptosis, the promotion of ferroptosis and the activation of the GRP78-PERK-CHOP pathway. Overall, ERS facilitates neuronal damage in neonatal HIBD by inducing ferroptosis. Consequently, the suppression of ERS may represent a promising therapeutic strategy for treating neonatal HIBD.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"805-815"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702982","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":"Structural and Functional Characterization of Obesumbacterium proteus Phytase: A Comprehensive In-Silico Study.","authors":"Asmita Kamble, Rajkumar Singh, Harinder Singh","doi":"10.1007/s12033-024-01069-x","DOIUrl":"10.1007/s12033-024-01069-x","url":null,"abstract":"<p><p>Phytate, also known as myoinositol hexakisphosphate, exhibits anti-nutritional properties and possesses a negative environmental impact. Phytase enzymes break down phytate, showing potential in various industries, necessitating thorough biochemical and computational characterizations. The present study focuses on Obesumbacterium proteus phytase (OPP), indicating its similarities with known phytases and its potential through computational analyses. Structure, functional, and docking results shed light on OPP's features, structural stability, strong and stable interaction, and dynamic conformation, with flexible sidechains that could adapt to different temperatures or specific functions. Root Mean Square fluctuation (RMSF) highlighted fluctuating regions in OPP, indicating potential sites for stability enhancement through mutagenesis. The systematic approach developed here could aid in enhancing enzyme properties via a rational engineering approach. Computational analysis expedites enzyme discovery and engineering, complementing the traditional biochemical methods to accelerate the quest for superior enzymes for industrial applications.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"588-616"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932066","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":"FDA-Approved Chimeric Antigen Receptor (CAR)-T Cell Therapy for Different Cancers-A Recent Perspective.","authors":"R Thirumalaisamy, S Vasuki, S M Sindhu, T M Mothilal, V Srimathi, B Poornima, M Bhuvaneswari, Mohan Hariharan","doi":"10.1007/s12033-024-01090-0","DOIUrl":"10.1007/s12033-024-01090-0","url":null,"abstract":"<p><p>Cancer is one of the most prevalent diseases in the world, and their rate of occurence has been increased in recent decades. Current review article, summarizes the novel treatment options Chimeric Antigen Receptor-T (CAR-T) cell therapy for various cancers constitute a major health and development challenge, impacting every aspect of sustainable development quoted by goal 3 good health and well-being of UN sustainable goals. WHO estimates that 70% of cancer deaths occur in low- and middle- income countries (LMICs) by 2030, LMICs are expected to bear the brunt of the expected 24.1 million new cancer cases per year. This current review article focuses and discussed about CAR-T cell therapy for various cancers against most prevalent non-communicable disease cancer disease stipulated by WHO and UN sustainable goals. Three literature databases Google scholar, Science Direct, PubMed was utilized to search and collect CAR-T cell treatment options for different cancers published articles sources in between January 2000 and December 2023. There were a total of 18,700 papers found, with 48 of them being found to be eligible focusing various cancer treatment by CAR-T cells utilized for the study. Based on the information gathered, CAR-T cell therapy treating different cancers and their merit and its advantages in heal and improve certain cancers was also discussed in this review article with their detailed molecular mechanisms. This article also gives an insight to utilize CAR-T cell treatment protocols for rejuvenating cancer patient from such ruthless cancer disease condition thereby improving life span of cancer patients and eradication of disease in some cases.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"469-483"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065562","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":"Development of Polyclonal Antibodies-Based Serological Method for the Detection of Calanthe Mild Mosaic Virus and Application in Virus Certification Programme.","authors":"Nishant Srivastava, Rakesh Kumar, Reetika Kapoor, Ashwini Kumar, Susheel K Sharma, Nitika Gupta, Pooja Bhardwaj, Gopi Kishan, Rajendra P Pant, Virendra K Baranwal","doi":"10.1007/s12033-024-01074-0","DOIUrl":"10.1007/s12033-024-01074-0","url":null,"abstract":"<p><p>Calanthe mild mosaic virus (CalMMV) infecting orchids is an important potyvirus which is known to cause mild leaf mosaic and flower colour-breaking symptoms in Calanthe and other orchid plants. The present study reports the production of polyclonal antibodies against CalMMV using bacterially expressed recombinant coat protein as immunogen, which in turn would be useful in routine indexing and screening of orchid germplasm. The coat protein (CP) gene (~ 807 bp) of CalMMV isolated from infected orchid sample was cloned in expression vector, pET-28a ( +) that yielded ~ 31 kDa fusion protein with Histidine tag (His₆BP). The expression of fusion CP was confirmed through SDS-PAGE and Western blotting. The His₆BP-CalMMV-CP obtained in soluble state after purification was used to immunize New Zealand white rabbit for the production of polyclonal antibodies (PAb). The PAb produced against the purified fusion protein successfully detected CAlMMV in the orchid samples at a dilution of 1:2000 in direct antigen-coated enzyme-linked immunosorbent assay (DAC-ELISA). This study presents the first report of Histidine tag (His₆BP) fusion CalMMV-CP-based antibody production and its successful application in the identification of the virus in orchid plants. Outcome of this study will be helpful in routine certification programmes, screening of orchid germplasm and production of CalMMV-free planting materials of orchids.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"628-637"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747038","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":"Engineering Camelina sativa Seeds as a Green Bioreactor for the Production of Affordable Human Pro-insulin that Demonstrates Anti-diabetic Efficacy in Rats.","authors":"Sapna Bhoria, Priyanka Saini, Darshna Chaudhary, Ranjana Jaiwal, Pawan K Jaiwal","doi":"10.1007/s12033-024-01068-y","DOIUrl":"10.1007/s12033-024-01068-y","url":null,"abstract":"<p><p>The current production of recombinant insulin via fermenter-based platforms (Escherichia coli and yeast) could not fulfill its fast-growing commercial demands, thus leading to a great interest in its sustainable large-scale production at low cost using a plant-based system. In the present study, Agrobacterium tumefaciens-mediated nuclear stable genetic transformation of an industrial oilseed crop, Camelina sativa, to express pro-insulin (with three furin endoprotease cleavage sites) fused with cholera toxin B subunit (CTB) in their seeds was successfully achieved for the first time. The bar gene was used as a selectable marker for selecting transformants and producing herbicide-resistant camelina plants. The transformation process involved the infiltration of camelina inflorescences (at flower buds with partially opened flowers) with A. tumefaciens and harvesting the seeds (T₀) at maturity. The T₀ seeds were raised into the putative T₁ plants sprayed with Basta herbicide (0.03%, v/v), and the survived green transformed plants tested positive for pro-insulin and bar genes. A transformation frequency of 6.96% was obtained. The integration and copy number of the pro-insulin transgene and its expression at RNA and protein levels were confirmed in T₁ plants using Southern hybridization, semi-quantitative Reverse Transcriptase-Polymerase Chain Reaction (sqPCR), and quantitative real-time Time PCR (qPCR) and western blot analysis, respectively. Enzyme-linked immunosorbent Assay (ELISA) quantified the amount of expressed pro-insulin protein, and its anti-diabetic efficacy was validated in diabetic rats on oral feeding. Transgenic plants integrated the pro-insulin gene into their genomes and produced a maximum of 197 µg/100 mg of pro-insulin (0.804% of TSP) that had anti-diabetic efficacy in rats.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"575-587"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898139","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":"Hypoxia-Challenged Pancreatic Adenocarcinoma Cell-Derived Exosomal circR3HCC1L Drives Tumor Growth Via Upregulating PKM2 Through Sequestering miR-873-5p.","authors":"Luoluo Wang, Shuping Zhou, Yi Ruan, Xiang Wu, Xueming Zhang, Yi Li, Dongjian Ying, Yeting Lu, Yuan Tian, Gong Cheng, Jing Zhang, Kaiji Lv, Xinhua Zhou","doi":"10.1007/s12033-024-01091-z","DOIUrl":"10.1007/s12033-024-01091-z","url":null,"abstract":"<p><p>Pancreatic adenocarcinoma (PAAD) is a fatal disease with poor survival. Increasing evidence show that hypoxia-induced exosomes are associated with cancer progression. Here, we aimed to investigate the function of hsa_circ_0007678 (circR3HCC1L) and hypoxic PAAD cell-derived exosomal circR3HCC1L in PAAD progression. Through the exoRBase 2.0 database, we screened for a circular RNA circR3HCC1L related to PAAD. Changes of circR3HCC1L in PAAD samples and cells were analyzed with real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, migration, invasion were analyzed by colony formation, cell counting, and transwell assays. Measurements of glucose uptake and lactate production were done using corresponding kits. Several protein levels were detected by western blotting. The regulation mechanism of circR3HCC1L was verified by dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Exosomes were separated by differential ultracentrifugation. Animal experiments were used to verify the function of hypoxia-derived exosomal circR3HCC1L. CircR3HCC1L was upregulated in PAAD samples and hypoxic PAAD cells. Knockdown of circR3HCC1L decreased hypoxia-driven PAAD cell proliferation, migration, invasion, and glycolysis. Hypoxic PAAD cell-derived exosomes had higher levels of circR3HCC1L, hypoxic PAAD cell-derived exosomal circR3HCC1L promoted normoxic cancer cell malignant transformation and glycolysis in vitro and xenograft tumor growth in mouse models in vivo. Mechanistically, circR3HCC1L regulated pyruvate kinase M2 (PKM2) expression via sponging miR-873-5p. Also, PKM2 overexpression or miR-873-5p silencing offset circR3HCC1L knockdown-mediated effects on hypoxia-challenged PAAD cell malignant transformation and glycolysis. Hypoxic PAAD cell-derived exosomal circR3HCC1L facilitated PAAD progression through the miR-873-5p/PKM2 axis, highlighting the contribution of hypoxic PAAD cell-derived exosomal circR3HCC1L in PAAD.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"762-777"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288578","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":"O-sialoglycoprotein Endopeptidase (OSGEP) Suppresses Hepatic Ischemia-Reperfusion Injury-Induced Ferroptosis Through Modulating the MEK/ERK Signaling Pathway.","authors":"Yuanyuan Tao, Wanqing Zhou, Cheng Chen, Qian Zhang, Zhuoyi Liu, Pingping Xia, Zhi Ye, Chunling Li","doi":"10.1007/s12033-024-01084-y","DOIUrl":"10.1007/s12033-024-01084-y","url":null,"abstract":"<p><p>Hepatic ischemia-reperfusion injury (HIRI) was widely accepted as a critical complication of liver resection and transplantation. A growing body of evidence suggested that O-sialoglycoprotein endopeptidase (OSGEP) was involved in cell proliferation and mitochondrial metabolism. However, whether OSGEP could mediate the pathogenesis of HIRI has still remained unclarified. This study investigated whether OSGEP could be protective against HIRI and elucidated the potential mechanisms. The OSGEP expression level was detected in cases undergoing ischemia-related hepatectomy and a stable oxygen-glucose deprivation/reoxygenation (OGD/R) condition in hepG2 cells. Additionally, it was attempted to establish a mouse model of HIRI, thus, the function and mechanism of OSGEP could be analyzed. At one day after hepatectomy, the negative association of OSGEP expression level with the elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was noted. Moreover, it was attempted to carry out gain- and loss-of-function analyses of OSGEP in hepG2 cells to reveal its influences on OGD/R-induced injury and relevant signaling pathways. The findings suggested that OSGEP overexpression significantly protected hepG2 cells against ferroptotic cell death, while OSGEP consumption had opposite effects. Consistent with in vitro studies, OSGEP deficiency exacerbated liver functions and ferroptotic cell death in a mouse model of HIRI. The results also revealed that OSGEP mediated the progression of HIRI by regulating the MEK/ERK signaling pathway. Rescue experiments indicated that ERK1/2 knockdown or overexpression reversed the effects of OSGEP overexpression or knockdown on hepG2 cells under OGD/R condition. Taken together, the findings demonstrated that OSGEP could contribute to alleviate HIRI by mediating the MEK-ERK signaling pathway, which may serve as a potential prognostic marker and a therapeutic target for HIRI.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"689-704"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140059951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}