Applied Biochemistry and Biotechnology最新文献

{"title":"6-Gingerol Inhibits Ferroptosis in Endothelial Cells in Atherosclerosis by Activating the NRF2/HO-1 Pathway.","authors":"Shuai Wang, Xiaoliang Song, Hui Gao, Yi Zhang, Xin Zhou, Fengrong Wang","doi":"10.1007/s12010-025-05214-3","DOIUrl":"https://doi.org/10.1007/s12010-025-05214-3","url":null,"abstract":"<p><p>Targeting endothelial cell ferroptosis is a potential approach for the treatment of atherosclerosis (AS). 6-Gingerol (6-Gin) is an active substance in ginger that is beneficial for improving AS. We conducted this study to explore whether 6-Gin mediated AS progression by regulating ferroptosis of endothelial cells. ApoE-/- mice were fed a high-fat diet to establish AS mouse model. Additionally, oxidized low-density lipoprotein (ox-LDL) was used to treat human umbilical vein endothelial cells (HUVECs) to generate injured cell model. Ferroptosis was evaluated by propidium iodide staining assay, western blot, and detecting iron, glutathione, malonaldehyde, and reactive oxygen species levels. The results showed that ox-LDL inhibited the proliferation and induced inflammation and ferroptosis of HUVECs, which was reversed by 6-Gin treatment. Moreover, 6-Gin upregulated HO-1 and NQO1 levels and promoted nuclear translocation of NRF2 in ox-LDL-treated HUVECs. ATRA, an NRF2 inhibitor, abrogated the promotion of proliferation and the inhibition of inflammation and ferroptosis induced by 6-Gin. Additionally, 6-Gin alleviated AS and suppressed ferroptosis in vivo. In conclusion, 6-Gin inhibited endothelial cell ferroptosis by inactivating the NRF2/HO-1 pathway, thereby improving abnormal lipid metabolism in AS mice. These findings suggest that 6-Gin may be a novel therapeutic drug for AS.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690689","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":"Constructing Genetically Engineered Escherichia coli for De Novo Production of L-Threo-3-Hydroxyaspartic Acid.","authors":"Jing Guo, Jiayi Cui, Mingyue Xun, Wencheng Zhang, Mo Xian, Rubing Zhang","doi":"10.1007/s12010-025-05224-1","DOIUrl":"https://doi.org/10.1007/s12010-025-05224-1","url":null,"abstract":"<p><p>L-threo-3-hydroxyaspartic acid (L-THA) is a non-proteinogenic amino acid that has garnered significant attention due to its diverse biological activities. However, the synthesis of L-THA through enzymatic and whole-cell catalysis requires the expensive substrate L-aspartic acid or L-asparagine, and co-substrate α-ketoglutarate, which limits their large-scale application. Here, this is the first report of engineering E. coli as a cell factory for de novo production of L-THA from glucose by fermentation. Firstly, the asnO gene encoding asparagine hydroxylases from Streptomyces coelicolor was heterologously expressed in E. coli to yield the L-THA producing strain. The formation and configuration of L-THA were characterized by LC-MS and HPLC after FDAA derivatization. Secondly, the pathway genes aspC and asnB, which encode aspartate aminotransferase and asparagine synthase, respectively, were overexpressed to enhance L-THA titer from 49.9 to 90.84 mg/L. Thirdly, the efforts were made to improve the key precursor L-aspartic acid pool by overexpressing the aspartase encoding gene aspA and knocking out aspartate kinase (AK) III encoding gene lysC. The best strain CC03 was obtained and L-THA titer reached 278.3 mg/L in a shake flask, representing an approximately 5.6-fold increase compared to the original strain. Ultimately, 2.87 g/L L-THA was obtained after 32 h fed-batch fermentation. This research underscores the potential use of E. coli fermentation as a feasible platform for de novo biosynthesis of L-THA from glucose, which is amenable to industrial application.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690641","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":"Mechanism of KDM4A in Regulating Microglial Polarization in Ischemic Stroke.","authors":"Jingliang Du, Xianyang Liang, Denghui Wang, Zhen Wang, Ruile Shen","doi":"10.1007/s12010-025-05207-2","DOIUrl":"https://doi.org/10.1007/s12010-025-05207-2","url":null,"abstract":"<p><p>Microglia polarization plays important roles in inflammatory processes after ischemic stroke. This study aimed to explore the mechanism of lysine-specific histone demethylase 4 (KDM4A) in microglia polarization after ischemic stroke. The mouse model was established using middle cerebral artery occlusion/reperfusion (MCAO/R) and the cell model was established by oxygen-glucose deprivation/reperfusion (OGD/R). The neurological deficits and brain tissue injury were evaluated. The biomarkers of microglia were determined. Levels of KDM4A/mouse double minute-2 homolog (MDM2)/C1q/TNF-related protein-3 (CTRP3) were measured. Inflammatory cytokines were quantified. The impact of KDM4A on microglia polarization was assessed. The enrichment of KDM4A or histone 3 lysine 9 trimethylation (H3K9me3) on the MDM2 promoter was analyzed. The ubiquitination and protein levels of CTRP3 after MG132 and cycloheximide treatment were determined. Results showed that KDM4A and MDM2 were upregulated while CTRP3 was downregulated. KDM4A downregulation alleviated neurological dysfunction, rescued motor capacity, reduced inflammatory infiltration, suppressed microglia activation, and promoted M2 polarization. KDM4A inhibited the enrichment of H3K9me3 on the MDM2 promoter, increasing MDM2 expression and downregulating CTRP3 expression via ubiquitination and degradation. MDM2 overexpression or CTRP3 downregulation averted the promotive role of silencing KDM4A in microglia polarization. In conclusion, KDM4A promotes microglia polarization to aggravate ischemic stroke via the MDM2/CTRP3 axis.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623016","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":"Antiviral Cellulose-Lignin Assembly Entirely Composed of Plant Cell Wall Components.","authors":"Chihiro Kimura, Eriko Ohgitani, Osam Mazda, Takashi Watanabe","doi":"10.1007/s12010-025-05184-6","DOIUrl":"https://doi.org/10.1007/s12010-025-05184-6","url":null,"abstract":"<p><p>Antiviral lignin, designated as FR₂₀₀, was produced using acidic microwave glycerolysis of sugarcane bagasse. The lignin strongly inhibited infection by the human norovirus surrogate, feline calicivirus (FCV) without substantial cytotoxicity. The antiviral activity emerged through direct contact of the lignin with the virion. To develop antiviral fibers, cotton was coated with the antiviral lignin AIF₂₀₀, a crude fraction obtained in the process of FR₂₀₀ preparation. Autofluorescence microscope images confirmed successful even coating of the lignin on the cellulose fiber surfaces. ATR FT-IR spectra supported the incorporation of the lignin. The strong anti-FCV activity of the cellulose-lignin assembly was observed by measuring viral titers of the filtrate passing through the lignin-immobilized cotton. The antiviral material developed in this study, totally composed of lignocellulosic biomass, is potentially useful for protecting our health by capturing virions in daily life and livestock environments.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571884","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":"Mesenchymal Stem Cell-Derived Exosome miR-153-3 Induced M2-Type Polarization of Macrophages to Improve the Healing Effect of Burn Wounds.","authors":"Chonggen Huang, Guozhong Lu, Zhigang Jia, Jiong Yan","doi":"10.1007/s12010-025-05196-2","DOIUrl":"https://doi.org/10.1007/s12010-025-05196-2","url":null,"abstract":"<p><p>The healing process of wounds, as soft tissue injuries, is challenging. Bone marrow mesenchymal stem cells (BMSCs) and exosomes (Ex) they secrete are critical for skin wound healing. Paracrine signaling mechanisms appear to facilitate the therapeutic properties of BMSCs. However, BMSC therapy has not yet been extensively explored in terms of specific cellular interactions between macrophages and BMSCs. In this study, macrophage depletion had a substantial negative impact on the wound healing capabilities of BMSCs, highlighting macrophages' crucial role in facilitating wound healing processes mediated by BMSCs. BMSCs transferred to the wound site promoted M2 polarization and alleviated wound healing. The co-cultivation of BMSCs and macrophages resulted in an enhanced phenotypic polarization towards M2. A mechanistic explanation for this effect was found in BMSCs-Ex. Additionally, miR-153-3p, derived from BMSCs-Ex, was identified as a regulator of macrophage polarization via its targeting of KPNA5. Through the transfer of BMSCs-Ex-derived miR-153-3p, BMSCs are capable of promoting M2 polarization and can potentially facilitate wound healing.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571903","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":"Bone Marrow Mesenchymal Stem Cell-Originated Exosomes Curb Oxidative Stress and Pyroptosis Triggered by Ovarian Ischemia/Reperfusion via the TXNIP/NLRP3 Inflammasome Pathway.","authors":"Min Xu, Min Don, Yiyuan Chen, Mingzhe Zhang","doi":"10.1007/s12010-025-05188-2","DOIUrl":"https://doi.org/10.1007/s12010-025-05188-2","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) and their secreted exosomes (Exos) have attracted much interest for their potential against ischemia/reperfusion injury (IRI). In the present research, we employed rat ovarian ischemia/reperfusion injury (OIRI) model and hypoxia/reoxygenation (H/R) model of primary rat ovarian granulosa cells (RGCs) to investigate whether BMSC-Exos could alleviate OIRI. Our data suggested that administration of BMSCs in rats significantly reduced OIRI-resultant histopathological changes, oxidative stress, inflammation, and pyroptosis. In addition, BMSCs downregulated the expression of proteins related to the TXNIP/NLRP3 inflammasome pathway. Based on in vitro experiments, BMSC-Exos could be internalized by RGCs and curbed oxidative stress and pyroptosis in H/R-injured RGCs. This effect may be due to the regulation of TXNIP/NLRP3 inflammasome pathway. Remarkably, our in vivo data were in concordance with our in vitro results, suggesting that BMSC-Exos suppressed OIRI-induced oxidative stress and pyroptosis via the TXNIP/NLRP3 inflammasome pathway. Overall, these results demonstrate good therapeutic efficacy of BMSC-Exos for treating OIRI, which may provide experimental evidence for the potential clinical benefits of BMSC-Exos for ovarian protection.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555529","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":"Inhibition of ATP Citrate Lyase by Hydroxycitrate-Loaded Exosomes Suppresses the Survival of Lung Adenocarcinoma Cells.","authors":"Kanika Phutela, Priyanca Ahlawat, Jyotdeep Kaur, Amanjit Bal, Navneet Singh, Harkant Singh, Sadhna Sharma","doi":"10.1007/s12010-025-05204-5","DOIUrl":"https://doi.org/10.1007/s12010-025-05204-5","url":null,"abstract":"<p><p>The metabolic enzyme ATP citrate lyase is overexpressed in several cancers and links glucose metabolism with de novo fatty acid synthesis pathway by catalyzing the conversion of citrate into acetyl CoA and oxaloacetate. Potassium hydroxycitrate, its natural inhibitor, exhibits anticancer activity; however, its use is limited due to low bioavailability. This study aims to improve the efficacy of hydroxycitrate by its encapsulation in bovine milk exosome surface conjugated with folate for targeting lung cancer cells. The mean particle size of potassium hydroxycitrate-loaded exosomes (Exo-KH) and paclitaxel exosomes (Exo-Pac) was 183 nm and 174 nm; they had spherical morphology and encapsulation efficiency of 16.87 ± 2.78% and 27.65 ± 3.23%, respectively. In the in vitro study, Exo-KH suppressed the proliferation of A549 cells and significantly reduced ACLY mRNA expression. In addition to ACLY, EXO-KH also downregulated the mRNA expression of other crucial metabolic enzymes such as fatty acid synthase and isocitrate dehydrogenase 1. EXO-KH formulation caused significant increase in apoptosis rate (< 75%) and reactive oxygen species production and reduced ACLY protein expression in A549 cells. Moreover, the pharmacokinetic study revealed the sustained release of hydroxycitrate (half-life 22.74 h and clearance 0.13 µg/ml) from the exoformulation. Altogether, the study findings highlight the beneficial role of EXO-KH formulation against lung cancer.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536305","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":"One-Pot Synthesis and Characterization of Naringenin-Capped Silver Nanoparticles with Enhanced Biological Activities.","authors":"Neelima Sathianathan, Vipina Vinod Thazhenandayipurath, Aparna Vadakoot Mukundan, Aparna Raj, Vidya Latha, Radhakrishnan Edayileveetil Krishnankutty, Sudarsanakumar Chellappanpillai","doi":"10.1007/s12010-025-05181-9","DOIUrl":"https://doi.org/10.1007/s12010-025-05181-9","url":null,"abstract":"<p><p>Flavonoids are known to possess biological effects like anti-inflammatory, antibacterial, antioxidant, and antidiabetic properties. Similarly, silver nanoparticles (AgNPs) have been widely used in the biomedical industry for therapy and diagnostics for a long time. This study investigates the potential of naringenin functionalized silver nanoparticles (AgN NPs) as a potential wound healing agent. The synthesis of AgN NPs was carried out using the one-pot synthesis method in the alkaline pH. Naringenin is used as the capping and the reducing agent. The naringenin-capped AgNPs were synthesized in six different concentrations. The structural, morphological, and spectroscopic characterization for each sample was conducted. The size of the nanoparticles was studied using the dynamic light scattering (DLS) experiment and further confirmed using TEM. The crystalline structure was investigated using X-ray diffraction, and AgN NPs exhibited a fcc crystal structure. The FTIR confirmed the capping of naringenin on AgNPs. All samples were tested for antibacterial activity, and the results demonstrated zones of inhibition against both Gram-positive Staphylococcus aureus and Gram-negative bacteria, such as Escherichia coli and Pseudomonas aeruginosa. Also, AgN NPs exhibited dose-dependent anti-inflammatory, antioxidant, and antidiabetic properties. The wound healing potential of AgN NPs was evaluated using a scratch wound assay in L929 cell lines. After 24 h, the scratch area was significantly reduced in the AgN NPs-treated sample, indicating enhanced cell migration compared to naringenin. Hence, these findings suggest that AgN NPs may serve as a more promising wound-healing agent than naringenin.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497444","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":"An Integrative Approach Using Molecular and Metabolomic Studies Reveals the Connection of Glutamic Acid with Telomerase and Oxidative Stress in Berberine-Treated Colorectal Cancer Cell Line HCT 116.","authors":"Muhammad Azizan Samad, Arief Izzairy Zamani, Nazia Abdul Majid, Saiful Anuar Karsani, Syarul Nataqain Baharum, Jamilah Syafawati Yaacob, Mohd Zuwairi Saiman","doi":"10.1007/s12010-025-05200-9","DOIUrl":"https://doi.org/10.1007/s12010-025-05200-9","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the common deadliest cancers worldwide. In Malaysia, the numbers of new CRC cases were horrific and worrisome. Telomerase is both prognostic indicator and predictor of carcinogenesis in CRC patients. Berberine, a telomerase inhibitor, was used in clinical trials and metabolomic studies; however, the association of telomerase with metabolites and metabolic pathways was not fully understood. Colorectal cancer cell line HCT 116 was cultured and treated with 10.54 µg/mL berberine. The cells were harvested at different time points to conduct subsequent analyses. The methods used in this research were real time-polymerase chain reaction (RT-PCR) to assess RNA expressions; Western blot to determine protein levels; TELOTAGGG Telomerase PCR ELISA to determine relative telomerase activity (RTA); 4',6-diamidino-2-phenylindole (DAPI) staining to determine percentage of nuclei damage; fluorescence microscopy for cell area; spectrophotometric potassium iodide assay for intracellular hydrogen peroxide concentration [H₂O₂]; as well as liquid chromatography mass spectrometry (LCMS) and tandem mass spectrometry (MS/MS) to investigate the intracellular metabolites. Partial least square-discriminant analysis (PLS-DA) score plot exhibited an improved separation compared to principal component analysis (PCA) when metabolomic data analysis of HCT 116 at various berberine treatment durations was conducted. Time and berberine treatment had an impact on RTA in HCT 116. RTA was discovered to be positively and negatively correlated to 14 and 2 metabolites, respectively. Glutamic acid was consistently found correlated to RTA. Other four metabolites, i.e., MG(14:0), [3-[hydroxy(phosphonooxy)phosphoryl]oxyphenyl] phosphono hydrogen phosphate), (3S,6S)-6-[[(3S,6R)-6-[(2S,3S,5S)-2,5-diiodo-4-methoxy-6-methyloxan-3-yl]oxy-3,4,5-trihydroxyoxan-2-yl]methoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid, and 1-[5-O-(5'-adenylyloxyphosphonyl)-beta-D-ribofuranosyl]-5-amino-1H-imidazole-4-carboxamide, were newly discovered to be connected to RTA in HCT 116. Four metabolic pathways that majorly affected shared glutamic acid and glutamine. Nitrogen metabolism, D-glutamine and D-glutamate metabolism, glyoxylate and dicarboxylate metabolism, and aminoacyl-tRNA biosynthesis have been identified to be associated with RTA. Network analyses hinted that glutamic acid was also associated with oxidative stress mechanism. The multiple roles glutamic acid acted in diverse metabolic pathways and interaction networks emphasized the importance of glutamic acid in HCT 116 regarding RTA. This research establishes the association between RTA and several chosen RNAs, proteins, metabolites, and oxidative stress mechanisms, consequential in morphological alteration in HCT 116, to expand the knowledge of the intricate biological relationships and telomerase mechanism in CRC.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497888","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":"Identification of Subtypes and Diagnostic Markers Related to Necroptosis in Sepsis.","authors":"Sen Peng, Ning Meng, Xia Xie, Bing Zhu, Bing Wang","doi":"10.1007/s12010-025-05201-8","DOIUrl":"https://doi.org/10.1007/s12010-025-05201-8","url":null,"abstract":"<p><p>Sepsis is a serious systemic infection with a high mortality rate. More and more evidence suggested that necroptosis plays a crucial role in the pathogenesis and progression of sepsis. This study aimed to elucidate the biological function and clinical significance of necroptosis in sepsis, and identify new potential biomarkers to improve the diagnosis and treatment of sepsis. Firstly, we identified 40 differentially expressed necroptosis related genes (DENRGs). Subsequently, a protein interaction (PPI) network of 40 DENRGs was constructed. Based on the key NRGs in the PPI network, the LASSO algorithm was used to screen eight diagnostic-related NRGs in sepsis, and a diagnostic model and risk score were constructed. The ROC analysis results indicated that the eight NRGs diagnostic model has good diagnostic performance (AUC = 0.955). There is a significant difference in risks core between normal samples and sepsis patients. The results of immune infiltration analysis showed that eight diagnostic-related NRGs were significantly correlated with multiple immune cells. Given the clinical significance of necroptosis in sepsis, we identified two molecular subtypes of sepsis based on eight NRGs. The necroptosis score of subtype 1 is significantly lower than that of subtype 2, while the immune score of subtype 1 is significantly higher than that of subtype 2. In summary, we developed and validated a diagnostic model and risk score based on eight NRGs, and identified two completely different subtypes associated with sepsis. Our research may provide new insights into the mechanisms of necroptosis in sepsis and the identification of potential biomarkers.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497499","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}