Applied Biochemistry and Biotechnology最新文献

{"title":"Exploring Antibacterial, Antioxidant, Cytotoxic Potential of Oscillatoria sp.-Derived Metabolites and Their Molecular Docking with Estrogen Receptor-α.","authors":"Santhosh Sigamani, Balasubramani Govindasamy, Balashanmugam Panneerselvam, Jothimani Kannupaiyan, Sivanandam Magudeeswaran, Dhandapani Ramamurthy, Hemalatha Natarajan","doi":"10.1007/s12010-025-05246-9","DOIUrl":"https://doi.org/10.1007/s12010-025-05246-9","url":null,"abstract":"<p><p>Anthropogenic activities have led to the accumulation of carcinogenic toxicants in the food chain, posing severe risks to both human and animal health. Bioactive molecules derived from terrestrial and aquatic systems offer promising solutions to various health challenges. Presently, the cyanobacterial metabolites from ethyl acetate extract of Oscillatoria sp. (EAEOs) were evaluated for its antiproliferative, antioxidant, and antimicrobial effects. The EAEOs resulted significant antibacterial zones (12 ± 2.5, 17 ± 1.7, 14 ± 0.3, and 14 ± 2.6 mm) on Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Bacillus cereus, respectively. EAEOs also exhibited free radical scavenging activity with IC₅₀ values of 69.68 µg/mL (DPPH) and 144.4 µg/mL (hydroxyl radicals). Followed by, the EAEOs also exhibited significant inhibition of MCF-7 breast cancer cells (IC50: 54.25 µg/mL) compared to HepG2 and A549 cells (72.6 and 85.6 µg/mL), respectively The EAEOs induced apoptosis and chromosomal damage on targeted cancer cells, and their DNA fragmentation were evidenced. Totally, 17 compounds from EAEOs were identified from GC-MS, in which 2-cyclopenten-1-one, 2-hydroxy-3-methyl (23); piperidine, 1, 4-dimethyl (13); 17-pentatriacontene (7.88); and 3-octadecene (7.09%) are major ones. Molecular docking confirmed that acetamide, n-(2-benzoyl-4chlorophenyl)-2-(2-methylpiperidin-1-yl)- (compound-3) showed strong binding affinity (10.13 kcal/mol) with ERα. Overall, the biological potential of Oscillatoria metabolites were found to be significant. Hence, further screening of preponderant compounds and studying the mechanism are warranted to fulfill their applications in food, pharmaceuticals, and other industries.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957663","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":"Trigonelline Shields Chondrocytes from Oxidative Damage in Osteoarthritis through Activation of the Keap1/Nrf2/ARE Signaling Pathway.","authors":"Chunmei Jiang, Xiaohong He, Aiju Lou, Shiwen He, Qixin Xie, Yuechun Wang, Shan Zhong, Weirong Wu, Qingchun Huang","doi":"10.1007/s12010-025-05232-1","DOIUrl":"https://doi.org/10.1007/s12010-025-05232-1","url":null,"abstract":"<p><p>Oxidative stress-induced chondrocyte damage is a key contributor to the progression of osteoarthritis (OA). While trigonelline (TG) possesses anti-inflammatory and antioxidant activities, its functional role and underlying mechanisms in OA remain unclear. In this study, the human chondrocyte cell line CHON-001 was treated with TG alone or in combination with IL-1β or ML385 for 24 h. Chondrocyte injury-related events were assessed using Cell Counting Kit-8 (CCK-8), flow cytometry with Annexin V-FITC/PI kit, Hoechst staining, the probe 2,7-Dichlorofluorescin diacetate (DCFH-DA), SA-β-gal staining, and SOD and MDA assay kits. Our data revealed that TG alleviated IL-1β-induced inflammation, apoptosis, extracellular matrix (ECM) degradation, senescence, and oxidative stress in chondrocytes, accompanied by the downregulation of Keap1 and upregulation of Nrf2, HO-1 and NQO1. ML385 treatment reversed the protective effects of TG against IL-1β-induced injury in chondrocytes. In vivo, the anterior cruciate ligament transection (ACLT) was used to induce a rat OA model, and TG was administered by gavage. OA severity and articular cartilage degradation were evaluated by hematoxylin and eosin (H&E), toluidine blue, Safranin-O staining, and Osteoarthritis Research Society International (OARSI) scoring system. The in vivo data showed that TG attenuated the degeneration and erosion of articular cartilage, suppressed inflammation, and downregulated the levels of Keap1 and iNOS, while upregulating the levels of Nrf2 and Col2a1. In conclusion, our study demonstrated that TG inhibits oxidative stress-induced chondrocyte dysfunction and cartilage degradation by activating the Keap1/Nrf2/ARE signaling pathway.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955866","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":"Unraveling the Role of Microbes in Remediation of High Molecular Weight Polycyclic Aromatic Hydrocarbon Persistence in the Environment.","authors":"Tony Hadibarata, Kitara Pranareswari Hadibarata","doi":"10.1007/s12010-025-05245-w","DOIUrl":"https://doi.org/10.1007/s12010-025-05245-w","url":null,"abstract":"<p><p>The persistence and recalcitrance of high molecular weight polycyclic aromatic hydrocarbons (HMW-PAHs) are potential threats to health and the environment. They result mainly from incomplete combustion of fossil fuels and organic materials, and they tend to accumulate in terrestrial and aquatic ecosystems (particularly in soils, sediments, and water sources). Chronic exposure to HMW PAHs is associated with some of the most dreadful health outcomes, including lung and skin cancers and disorders of the respiratory and immune systems. The study therefore proposes microbial degradation as a promising bioremediation technique for HMW PAHs: pyrene, benzo[a]pyrene, chrysene, and fluoranthene. Aerobic degradations mediated by dioxygenase and dehydrogenase enzymes, as well as anaerobic pathways involving sulfate- and nitrate-reducing bacteria, are discussed. Factors that promote microbial degradation include pH, temperature, nutrient availability, and salinity. While all factors can be biostimulation and bioaugmentation, the study emphasizes these two as effective methods to enhance bioavailability and degradation efficiency. The results provide insightful information for further development of microbial techniques in remediation of HMW PAH-contaminated sites.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957025","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":"Anaerobic Volatile Fatty Acid Production Performance and Microbial Community Characteristics from Solid Fraction of Alkali-Thermal Treated Waste-Activated Sludge: Focusing on the Effects of Different pH Conditions.","authors":"Xiu-Fang Li, Wen-Shuai Zhang, Sheng Qi, Jun-Feng Zhao, Zhao-Yong Sun, Yue-Qin Tang","doi":"10.1007/s12010-025-05244-x","DOIUrl":"https://doi.org/10.1007/s12010-025-05244-x","url":null,"abstract":"<p><p>The waste-activated sludge (WAS) is rich in organic matter and various nutrients. Alkali-thermal hydrolysis of WAS can be employed to produce a liquid fertilizer with high plant-promoting nutrient content. However, the solid fraction (abbreviated as SF) generated from this process requires further treatment. Although there have been studies on the recovery of plant nutrients from WAS via alkali-thermal hydrolysis, researches on the safe treatment of the SF are limited. This study aims to explore the potential and the microbiological mechanisms on anaerobic volatile fatty acid (VFA) production from the SF under different pH conditions (i.e., 6, 7, 8, 9, and 10). The results showed that the VFA yield was highest at pH 6, reaching 4095.84 mg COD/L (i.e., 0.16 g-COD/g-volatile solids), followed by pH 10, 8, 7, and 9, with acetate being the main component (> 56%). Microbial community analysis revealed that members in phyla Firmicutes and Bacteroidota constituted the main acid-producing microbial community during the anaerobic fermentation of SF. Furthermore, different pH conditions influenced the yield and composition of VFAs by altering the structure and functions of microbial community. This research provides a new direction for the fully resourceful utilization of sludge by producing both liquid fertilizer and VFAs from WAS.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957079","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":"Decolorization of Azo and Anthraquinone Dyes Using Recombinant Horseradish Peroxidase A2A Isoenzyme Produced by Komagataella phaffii.","authors":"Nurgul Abul, Seyda Yildiz Arslan, Yagmur Unver, Hasan Ozdemir","doi":"10.1007/s12010-025-05239-8","DOIUrl":"https://doi.org/10.1007/s12010-025-05239-8","url":null,"abstract":"<p><p>Water pollution is a significant issue due to industrialization and population growth, and one of the main sources of wastewater is synthetic dyes. The textile sector is particularly affected by dyes like azo and anthraquinone dyes, which are difficult to degrade and produce toxic organic waste. Currently, synthetic dyes are processed through physical and chemical methods, which have financial and methodological disadvantages. Horseradish peroxidase (HRP) is a widely studied enzyme for purifying pollutants like dyes and phenols in wastewater. However, their high cost makes them a costly option. Recombinant protein production is suitable for the mass production of stable and resistant enzymes. In this study, the decolorization potential of recombinant HRP A2A (rHRP A2A) isoenzyme secreted by Komagataella phaffii and purified by affinity technique in a single step on Acid blue 113, Alizarin red, and Remazol brilliant blue R was presented for the first time, and the optimal conditions for the highest decolorization rate were determined. Fe²⁺ and Mn²⁺ metal ions increased enzyme activity by 158.62% and 79.54%, respectively. Color removal with 0.006 EU/mL rHRP A2A for Acid blue 113, Alizarin red, and Remazol brilliant blue R was observed at 71.27, 62.26, and 31.22%, respectively. ABTS served as a redox mediator, significantly increasing the rate of dye decolorization in a shorter period at the specified concentration.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955332","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":"Biocatalytic Synthesis of N-trans-feruloyltyramine Using an Amide Bond Synthetase with an ATP Recycling.","authors":"Bingshan Zhao, Jason Micklefield, Yonghua Wang, Fanghua Wang","doi":"10.1007/s12010-025-05250-z","DOIUrl":"https://doi.org/10.1007/s12010-025-05250-z","url":null,"abstract":"<p><p>N-trans-feruloyltyramine (FLA) is one kind of phenylpropanoid compound found in various plants. Numerous studies have confirmed that it exhibits a wide range of physiological functions, such as antioxidant, ɑ-glucosidase inhibition, and anti-inflammatory activity. However, the low content of FLA in plants greatly limits its potential use in food and pharmaceutical industries. It is, therefore, very important to establish an effective synthesis of FLA. In this study, a green and efficient method to synthesize FLA was sought using an amide bond synthetase (ABS) biocatalyst. Ten kinds of ABS enzymes, including AlCfaL from Azospirillum lipoferum, were screened as the potential biocatalysts for the production of FLA. To obtain optimum reaction conditions, the effects of various parameters on conversion of FLA were firstly evaluated. Under the optimum conditions using 1 mM N-trans-ferulic acid, 50 mM tyramine (substrate ratio of 1:50), 10 mM MgCl₂, 8 mM ATP, and 35 µM AlCfaL enzyme at 30 °C with a shaking speed of 500 r/min for 48 h, maximum conversion rate of 74% was reached. Given that the amidation reaction is mediated by relative expensive ATP, we further optimized reaction systems to incorporate an ATP recycling system consisting of a polyphosphate kinase enzyme (CHU) and an inexpensive polyphosphate (PolyP) as the phosphate donor. Response surface methodology (RSM) based on five-level, five-variable central composite design (CCD) was used to evaluate the optimal parameters for the production of FLA. The effects of AMP, PolyP, AlCfaL, CHU concentrations, and reaction time on the conversion rate of FLA were analyzed. The optimum conditions derived via RSM were 7.12 mM AMP, 5.96 mg/mL PolyP, 39.72 μM AlCfaL, 27.68 μM CHU, and a reaction time of 36 h. Validation experiments conducted under these optimized conditions yielded an actual conversion rate of 63.5%, which compared well to the maximum predicted value of 64.2%.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955095","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":"Untargeted Metabolomics Revealed Metabolomic Profile in Patients with Primary Systemic Sclerosis.","authors":"Jinling Tang, Pinglang Ruan, Zhu Wei","doi":"10.1007/s12010-025-05249-6","DOIUrl":"https://doi.org/10.1007/s12010-025-05249-6","url":null,"abstract":"<p><p>Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by increased morbidity and mortality. The intestinal microbiome and serum metabolites had been implicated in SSc, but the connection between the gut microbiome and serum metabolites remains poorly understood. In this study, we aimed to investigate the relationship between the gut microbiome and serum metabolome in SSc patients. Untargeted metabolomics was employed to examine the metabolic profiles of SSc patients. The results revealed significant alterations in metabolic pathways, particularly beta-alanine metabolism and pyrimidine metabolism in SSc patients. Specifically, reductions in spermine and beta-alanine were observed within beta-alanine metabolism, while uridylic acid decreased in pyrimidine metabolism. Furthermore, fecal microbiome analysis showed an increased relative abundance of Firmicutes, Verrucomicrobia, and Proteobacteria in SSc patients, whereas the abundance of Bacteroidetes and Actinobacteria was reduced at the phylum level. KEGG pathway analysis, combined with transcriptomic analysis of peripheral blood from SSc patients, identified upregulation of Toll-like receptor signaling, TNF signaling, lipid and atherosclerosis pathways, IL-17 signaling, and AMPK signaling. In summary, we performed a comprehensive analysis of the metabolic profile, which may provide insights for understanding the mechanisms of SSc.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955869","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 Optimized Droplet Digital PCR Assay for HER2 Copy Number Variation in Breast Cancer Based on Multi-reference Genes.","authors":"Jinbing Xue, Houshi Ma, Xiaoliang Zhang, Shun Wang, Jinxian Wang, Zeqin Li, Xi Wu, Tianhang Yang, Changsong Zhang, Gangyin Luo","doi":"10.1007/s12010-025-05233-0","DOIUrl":"https://doi.org/10.1007/s12010-025-05233-0","url":null,"abstract":"<p><p>Targeted therapy is essential for the 15-30% invasive breast cancer patients with human epidermal growth factor receptor 2 (HER2) over-expression. However, current HER2 diagnosing methods rely on complex manual works and highly subjective interpretations. To more accurately and objectively assess the HER2 amplification status of formalin fixed paraffin embedded (FFPE) samples, a droplet digital PCR (ddPCR) assay based on multi-reference genes was developed. We established a four-fluorescence ddPCR assay using breast cancer cell lines (T-47D and SK-BR-3) and validated it on 101 clinical breast cancer FFPE samples. Compared to clinicopathological results, the ddPCR assay based on two out of three reference genes demonstrated superior sensitivity (82.6%), specificity (98.7%), and consistency (95.0%) in determining HER2 status over assays using single or three reference genes. Whole genome sequencing of the abnormal cases further confirmed that the ddPCR assay outperformed clinical immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and quantitative PCR (qPCR) in accuracy. Our findings demonstrate that the multi-reference gene ddPCR assay significantly improves the accuracy of HER2 status detection and reduces errors associated with chromosome 17 abnormalities. This method holds promise as a complementary or alternative approach to conventional IHC and FISH testing in tissue biopsies and is also feasible for liquid biopsies.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958834","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":"Influence of Polystyrene Microplastics on Mitochondrial Oxidative Damage in Renal and Muscular Tissues of the Freshwater Fish.","authors":"Moothedath Arya, Kuttichira Jithila, Reeha Mashirin, Kumari Chidambaran Chitra","doi":"10.1007/s12010-025-05236-x","DOIUrl":"https://doi.org/10.1007/s12010-025-05236-x","url":null,"abstract":"<p><p>Polystyrene microplastics (PS-MPs), an emerging environmental contaminant, have attracted significant concern in recent years. This study aimed to evaluate mitochondrial oxidative damage in renal and muscular tissues of the freshwater fish Anabas testudineus following exposure to environmentally relevant concentrations (13.6 mg L⁻¹ and 23.6 mg L⁻¹) of PS-MPs for 1, 7, and 15 days. Exposure to PS-MPs disrupted the antioxidant defense system within the mitochondrial compartments of renal and muscle tissues, leading to increased levels of hydrogen peroxide generation and lipid peroxidation. PS-MPs exposure altered metabolic functions in the mitochondrial fractions of kidney and muscle tissues, as evidenced by elevated activities of alanine aminotransferase and aspartate aminotransferase. Besides, exposure to PS-MPs resulted in a decline of tissue-specific marker enzymes, such as acid and alkaline phosphatases, in renal tissue, indicating tissue damage. Histological examinations revealed significant tissue damage, including necrosis of renal tubules, vacuolization, glomerular degeneration, and melanomacrophage aggregation in kidney tissues. In muscle tissues, the observed damages included myolysis, vacuolar degeneration, necrosis, and atrophy of muscle fibers. These findings suggest that oxidative stress induced by PS-MPs exposure disrupts metabolic functions in mitochondrial fractions, thereby providing valuable insights into nephrotoxicity and muscular toxicity in fish.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956199","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":"Bioinformatics Analysis Reveals Hub Genes Linked to Programmed Cell Death in Intervertebral Disc Degeneration.","authors":"Mingyang Zou, Shaobo Wu, Jundan Wang, Wenya Xue, Xince Sun, Luyu Liu, Pan Yin, Dageng Huang","doi":"10.1007/s12010-025-05243-y","DOIUrl":"https://doi.org/10.1007/s12010-025-05243-y","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IVDD) represents a severe chronic condition characterized by diverse programmed cell death (PCD) mechanisms serving as critical pathological features. The identification of key genes associated with cellular demise in IVDD is crucial for enhancing diagnostic and prognostic strategies. We extracted microarray-based transcriptomic multi-datasets from the GEO database, comprising 34 normal specimens (grade I/II) and 38 IVDD cases (grade III/IV). Nineteen PCD-associated genes encompassing multiple death modalities (including apoptosis, pyroptosis, ferroptosis, autophagy, necroptosis, cuproptosis, parthanatos, entotic cell death, netotic cell death, lysosome-dependent cell death, alkaliptosis, oxeiptosis, NETosis, immunogenic cell death, anoikis, paraptosis, methuosis, entosis, and disulfidptosis) were systematically curated from established studies. Pathway enrichment was evaluated through gene set variation analysis (GSVA), while weighted gene co-expression network analysis (WGCNA) facilitated the identification of core cell death-related genes, ultimately constructing a cell death signature (CDS) risk model via LASSO regression. Then, we found the significant upregulation of specific PCD pathways in IVDD specimens, particularly apoptosis, ferroptosis, autophagy, necroptosis, immunogenic cell death, anoikis, and disulfidptosis. Immune profiling revealed substantial infiltration of M0 macrophages in IVDD tissues, contrasting with predominant activated NK cells and M2 macrophages in control groups. Through integrative analysis by limma and WGCNA, we discerned 19 key PCD-related genes, subsequently identifying three gene targets (YWHAB, BID, and GSDME) for IVDD pathogenesis. This investigation culminated in developing a machine learning-driven prognostic model based on these biomarkers. Our study establishes a novel and comprehensive framework integrating IVDD with PCD mechanisms, proposing YWHAB, BID, and GSDME as promising diagnostic biomarkers and therapeutic targets for IVDD management.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955330","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}