Applied Biochemistry and Biotechnology最新文献

{"title":"Functional Annotation Identifies 3-Oxoacyl Synthase III as a Druggable Target in Nocardia asteroides FDAARGOS1485: A Multi-Tier Structure-Guided Computational Discovery of Marine-Derived Therapeutic Leads","authors":"Maharaja Muthuvairam Subbulakshmi,&nbsp;Manikandan Jayaraman,&nbsp;Prabhu Dhamodharan,&nbsp;Jeyaraman Jeyakanthan","doi":"10.1007/s12010-026-05921-5","DOIUrl":"10.1007/s12010-026-05921-5","url":null,"abstract":"<div><p>Nocardiosis is a global life-threatening disease that predominantly affects immunodeficient populations. This disease is caused by the nosocomial pathogen <i>Nocardia asteroides</i>. Existing therapeutics offer several limitations and challenges, highlighting the need for novel druggable targets. The pathogenic strain FDAARGOS1485 contains 6,521 proteins and has a higher completeness of 98%, as determined by CheckM analysis. Among these proteins, 863 (13.20%) hypothetical proteins (HPs) were designated as targets. The functional annotation pipeline identified 30 (4.40%) HPs, classified into 24 enzymes (80%), 2 transporters (6.66%), 2 binding proteins (6.66%), and 2 proteins involved in cell regulatory processes (6.66%). Metabolic pathway analysis revealed the functionally annotated 3-oxoacyl-synthase III protein (WP_223513777.1) as a promising target. The structure-based virtual screening approach identified three potential MNPs (CMNPD22130, CMNPD23347, and SWMDRR052) with favourable docking scores ranging from − 8.23 to − 10.05 kcal/mol and post-docking binding energy values between − 62.42 and − 72.91 kcal/mol. Remarkably, none of the candidates violated Lipinski’s rule (Ro5), and all exhibited satisfactory pharmacokinetic profiles and favourable DFT scores. Molecular dynamics and essential dynamics confirmed the stability of the MNP-bound 3-oxoacyl-synthase III complexes. Furthermore, by utilizing 40 diverse computational resources, the present study proposes potential MNPs against nocardiosis and warrants experimental validations to explore their therapeutic potential.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":"198 11","pages":"9258 - 9292"},"PeriodicalIF":3.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981726","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":"Multi-gene Regulation Based on Metabolites Analysis Reduces Nucleus Degradation and By-product Accumulation During Phytosterols Conversion to 9-Hydroxyandrost-4-ene-3,17-Dione","authors":"Siyuan Ma,&nbsp;Zuran Guo,&nbsp;Lvqing Xu,&nbsp;Xuedong Wang","doi":"10.1007/s12010-026-05939-9","DOIUrl":"10.1007/s12010-026-05939-9","url":null,"abstract":"<div><p><i>Mycobacterium neoaurum</i> HK86W is capable of converting phytosterols into the steroidal pharmaceutical intermediate 9-hydroxyandrost-4-ene-3,17-dione (9-OH-AD). In this study, systematic biotransformation product profiling during sterol transformation revealed that degradation of the steroidal nucleus and accumulation of multiple by-products are key factors limiting the industrial application of this process. Knockout of two newly identified 3-ketosteroid-Δ¹-dehydrogenase genes (<i>kstD4</i> and <i>kstD5</i>) effectively reduced degradation of the steroid nucleus caused by Δ¹-dehydrogenation. Meanwhile, the mechanisms underlying the generation of various major by-products were clearly elucidated. Through genetic modifications involving deletion of <i>salA</i> and overexpression of <i>kshA</i>, <i>hsd4A</i>, and <i>hsd4B</i>, a mutant strain HK86-V was successfully constructed to reduce by-product formation. In a 50 g/L phytosterol transformation system, the engineered strain significantly increased 9-OH-AD production from 21.97 g/L to 29.47 g/L, with a molar yield of 80.34%. Furthermore, by reducing the reaction rate and supplementing glucose as an auxiliary carbon source, the yield of 9-OH-AD was further enhanced to 32.14 g/L and the molar yield increased to 87.62% under optimized transformation conditions.</p></div>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":"198 11","pages":"8564 - 8575"},"PeriodicalIF":3.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981747","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":"Therapeutic Potential of Pirfenidone in Adenine-Induced Chronic Kidney Disease: An Integrated Experimental and In Silico Study","authors":"Al Darraji Raad kareem Alwan,&nbsp;Amjad Oraibi,&nbsp;Teeb Ali Al-Saady,&nbsp;Ali Almukram,&nbsp;Safaa Halool Mohammed,&nbsp;Ahmed Hamza AlShammari,&nbsp;Maryam Saleem,&nbsp;Musa A. Said,&nbsp;Musaab Dauelbait,&nbsp;Hafiz Muhammad Zohaib,&nbsp;Omar A. Almohammed","doi":"10.1007/s12010-026-05919-z","DOIUrl":"10.1007/s12010-026-05919-z","url":null,"abstract":"<div><p>Chronic kidney disease (CKD) is a progressive condition characterized by sustained loss of renal function, frequently accompanied by fibrosis and oxidative stress–mediated damage. In this study, adenine-induced CKD was used as an experimental model to assess the effects of pirfenidone. Rats fed a 0.75% adenine diet exhibited key features of renal dysfunction, including reduced body weight, kidney hypertrophy, elevated serum urea and creatinine, decreased creatinine clearance, polyuria, low urine osmolarity, increased urinary N-acetylglucosaminidase excretion, and reduced antioxidant activity. Pirfenidone at 200 mg/kg and 500 mg/kg improved several of these parameters, with the higher dose showing greater efficacy. This approach identified 14 overlapping genes associated with the predicted targets of pirfenidone and with those implicated in CKD. The genes were involved in fibrotic and immunoregulatory pathways responsible for extracellular matrix turnover, with TIMP-1 as the most central gene within the interactive network. Docking studies further indicated a likely interaction between pirfenidone and TIMP-1, with an estimated binding energy of − 6.43 kcal/mol and support from specific interactions, including hydrogen bonding with Ser100 as well as hydrophobic and polar contacts. These observations suggest that pirfenidone may support kidney function not only by improving biochemical and functional parameters but also by interacting with molecular components associated with disease progression.</p></div>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":"198 11","pages":"8934 - 8949"},"PeriodicalIF":3.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981729","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 and Biochemical Characterization of a Novel β-1, 3-glucanase for Efficient Preparation of Laminarin Oligosaccharides","authors":"Limin Ning,&nbsp;Yi Zhao,&nbsp;Xinyu Yuan,&nbsp;Hui Wang,&nbsp;Benwei Zhu","doi":"10.1007/s12010-026-05938-w","DOIUrl":"10.1007/s12010-026-05938-w","url":null,"abstract":"<div><p>Endo-β-1, 3-glucanase, also called laminarinase, is a key enzyme tool for laminarin biomass biorefinery and pretreatment in industry by hydrolyzing the laminarin polysaccharide into oligosaccharides. Cel2C, a novel kind of endo-β-1, 3-glucanase, was identified and characterized in this study. The name of Cel2C originates from the genus abbreviation of its source strain, <i>Cellulophaga lytica</i> (Cel), combined with an internal sequence identifier (2 C). It consisted of three domains formed by 507 amino acids, namely the N-terminal helix domain, the uncharacterized region and the TIM-like catalytic domain. Cel2C exhibited degrading activities to laminarin, β-glucan and sodium carboxymethyl cellulose (CMC-Na). Notably, it exhibited maximal activity (1.062 × 10⁴ nkat/mg, equivalent to ~ 636.203 U/mg) toward laminarin at pH 6.0 and 50 °C, and retained approximately 80% of its maximal activity below 40 °C within a pH range of 6.0–8.0. The Michaelis–Menten constant (<i>K</i>_m) and the maximum velocity (<i>V</i>_max) of the recombinant Cel2C for laminarin were determined as 7.433 mg/mL and 575.820 nkat/mg (equivalent to ~ 34.54 U/mg), respectively. HPLC and ESI-MS analysis indicated that Cel2C can degrade laminarin and β-glucan into oligosaccharides with degrees of polymerization (DPs) of 1–7. According to structural characteristics and molecular docking analysis, the catalytic mechanism of Cel2C is similar to Glycoside Hydrolase Family 5, with the highly conserved residues Glu336 and Glu420 acting as the proton donor and nucleophile, which is essential for the degradation of laminarin and β-glucan. These properties highlight the potential application of Cel2C as an endo-β-1, 3-glucanase in the biorefinery of laminarin biomass in related industries.</p></div>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":"198 11","pages":"8374 - 8390"},"PeriodicalIF":3.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975451","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":"Studying The Role of Aprotic and Protic Solvents on Extremophilic Laccase From Thermus thermophilus for Solvent-Mediated One-Pot Biocatalysis.","authors":"Rokesh Radhakrishnan","doi":"10.1007/s12010-026-05935-z","DOIUrl":"https://doi.org/10.1007/s12010-026-05935-z","url":null,"abstract":"<p><p>In present times, globally, solvent-mediated biocatalysis is gaining a pivotal role in sustainable biotechnological solutions for organic synthesis. The versatile green catalyst, laccase, a multicopper oxidoreductase, has gained significant importance in aromatic bioconversion in solvent systems. Laccases portray varied behavioral patterns and functionality in solvents. With this interest, the influence of aprotic polar organic solvents and a benchmark out-of-the-ordinary protic solvent, an ionic liquid, i.e., 1-Ethyl-3-methylimidazolium acetate (EmimOAc), on extremophilic laccase from Thermus thermophilus, TtL, was elucidated. In this study, a signal peptide engineering strategy was adopted for improved enzyme expression. The first 28 amino acids corresponding to the signal peptide from an evolutionarily close E. coli' s laccase, copper efflux oxidase, tagged as 'sp', were incorporated with TtL by replacing TtL's signal peptide (first 23 amino acids), hence, spTtL was attained. Furthermore, micro-anaerobic condition was followed to reduce inclusions, and spTtL was purified. Subsequently, the spTtL's thermal unfolding and its activity against EmimOAc, DMSO, and acetone were studied as a prime highlight. At higher organic solvents, the thermal unfolding of spTtL directly exhibited constraints in spTtL' s melting point, showing reduced thermal stability. Interestingly, at higher EmimOAc (10-20% V/V), spTtL' s stability was infinitesimally affected; however, only 40% activity was retained in 50% V/V EmimOAc. In EmimOAc, inhibition kinetics of spTtL indicated a mixed competitive and non-competitive inhibition. Conclusively, this work emphasizes thermal unfolding understanding of spTtL in acetone, DMSO, and EmimOAc, which serves as a prerequisite for aiming/tailoring solvent media for one-pot laccase-based catalysis.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975446","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":"Anti-Inflammatory Role of Exopolysaccharides in Osteoarthritis via Modulation of Redox and Inflammatory/Catabolic Signaling Networks.","authors":"Alaa Elmetwalli, Ashraf Elsayed, Samaa Ahmed El-Sakka, Ghadeer H Albalawi, Faisal H Altemani, Ahmed E Noreldin, Dalia Wael, Zeinab A Ali, Rabab A Mohamed, Mervat G Hassan","doi":"10.1007/s12010-026-05929-x","DOIUrl":"https://doi.org/10.1007/s12010-026-05929-x","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a leading cause of disability worldwide, characterized by progressive cartilage degradation, chronic inflammation, and joint structural deterioration. Beyond its physical burden, OA significantly impacts psychological well-being and socioeconomic stability. Current pharmacological treatments, such as meloxicam (Mel), provide symptomatic relief but fail to comprehensively address the inflammatory mechanisms driving OA progression while also posing risks like liver toxicity. The study was designed to test whether exopolysaccharide (EPS) improves cartilage structural integrity in a ciprofloxacin (CIP)-induced OA-like experimental arthropathy, with inflammatory, oxidative, and signaling markers serving as supportive mechanistic outcomes. The EPS-producing Bacillus altitudinis strain BAE2023 was identified via 16S rRNA sequencing, with EPS composition confirmed through GC/MS and FTIR analyses. Forty male albino rats were divided into five groups: control, CIP-induced OA-like experimental arthropathy, and treatment groups receiving EPS, Mel, or their combination. Results demonstrated that combined EPS and Mel therapy significantly improved joint structural parameters, improved the measured redox profile by increasing SOD, GST, and GSH and by lowering MDA, a marker of lipid peroxidation, and suppressed key circulating inflammatory mediators. Gene expression analysis revealed that EPS successfully modulated the Nrf2/Ho-1 and Cox-2/Mmp1a signaling axes, highlighting its role in inflammation resolution and joint repair. Histopathological evaluation further confirmed cartilage regeneration and reduced hepatic toxicity. By effectively modulating inflammation and oxidative stress, EPS emerges as a promising therapeutic strategy for managing disability-related OA. This study underscores the potential of EPS in enhancing joint health, minimizing medication-induced toxicity, and improving overall quality of life for individuals suffering from OA. Integrating EPS into OA treatment paradigms may offer a more holistic, a chondroprotective and structure-preserving effect to disability management.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975440","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":"LncRNA UCA1 Aggravated Microglia-mediated Neuroinflammation After Traumatic Brain Injury by Targeting miR-708-5p","authors":"Jing Tian,&nbsp;Chunyan Li,&nbsp;Xianlong Miao,&nbsp;Hangyi Tan,&nbsp;Tao Zhang,&nbsp;Min Tang,&nbsp;Faan Miao","doi":"10.1007/s12010-026-05899-0","DOIUrl":"10.1007/s12010-026-05899-0","url":null,"abstract":"<div><p>Secondary neuroinflammation following traumatic brain injury (TBI) is the key factor leading to neurological deterioration. LncRNA UCA1 exerts regulatory effects in multiple pathological processes, but its specific function and mechanism in TBI remain unclear. The aim of this study was to explore the role of UCA1 in neuroinflammation following TBI and to verify whether it regulates neural injury by miR-708-5p. The inflammatory model was built in BV-2 microglia by LPS stimulation. Transfection was utilized to regulate UCA1 and miR-708-5p expression in cells. CCK-8, flow cytometry, ELISA, and dual luciferase reporter assay were employed to evaluate cell viability, apoptosis, inflammatory factors, and targeting relationship. A mouse TBI model was established via controlled cortical impact. The expression of UCA1 and miR-708-5p in mice was interfered by injecting sh-UCA1 lentivirus and miR-708-5p antagomir. The neurological severity score‌, Morris water maze test, brain-water content, and inflammatory factors levels in brain tissue were assessed in mice from different treatment groups. UCA1 expression was upregulated in TBI patient serum. Cell experiments indicated that silencing UCA1 markedly inhibited LPS-induced apoptosis and inflammatory cytokine release in BV-2 cells. In vivo experiments showed that silencing UCA1 improved neurological deficits, spatial memory impairment, cerebral edema, and inflammatory responses in TBI mice. Dual luciferase reporter assays revealed that UCA1 directly targets and binds to miR-708-5p, and that miR-708-5p directly targets TLR4. Mechanistically, inhibition of miR-708-5p partially reversed the protective effect induced by silencing UCA1, and this effect was mediated at least in part through TLR4. UCA1 promotes microglial-mediated neuroinflammation and injury after TBI by negatively regulating miR-708-5p and subsequently modulating TLR4. Targeting the UCA1/miR-708-5p/TLR4 axis may offer new therapeutic strategies for TBI.</p></div>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":"198 11","pages":"8525 - 8542"},"PeriodicalIF":3.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975516","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":"Integrated ¹H-NMR Metabolomics and Growth Kinetics Uncover Three Distinct Metabolic Scenarios in Lactiplantibacillus pentosus P7 Fermentation of Plant-Derived Prebiotics","authors":"Nhat Huy Chu,&nbsp;Thi Khanh Linh Pham,&nbsp;Hoang Duc Le,&nbsp;Quang Trung Pham,&nbsp;Hoang Ha Chu","doi":"10.1007/s12010-026-05911-7","DOIUrl":"10.1007/s12010-026-05911-7","url":null,"abstract":"<div><p>Lactic acid bacteria (LAB) drive a broad range of food and biotechnological fermentations, the outcomes of which depend not only on the bacterial genotype but also on the chemical composition of the fermentation substrate. To resolve how a single strain reorganises chemically distinct plant matrices, we profiled fermentations of <i>Lactiplantibacillus pentosus</i> P7 (GenBank JBLMKZ000000000) on garlic, onion, and kiwifruit extracts prepared in water and 70% ethanol, using growth kinetics combined with solvent-suppressed 500-MHz proton nuclear magnetic resonance metabolomics over 48 h, and integrated the data with whole-genome pathway annotations. Three substrate-specific metabolic scenarios emerged. On garlic, P7 grew vigorously, with the water extract exceeding the de Man–Rogosa–Sharpe reference medium at every time point (peak ΔOD₆₀₀ of 9.38 versus 8.52 at 24 h) and accumulating sorbose, rhamnose, and the aromatic amino acids phenylalanine and tryptophan (3.04- to 3.70-fold increases), providing first metabolic evidence consistent with the strain’s four-copy <i>aroE</i> shikimate-dehydrogenase expansion. On onion, the lowest cell density coincided with the highest lactate output of the dataset (5.21-fold rise at 48 h), transient 5-hydroxymethylfurfural reduction, and accumulation of acetoin and 1,3-propanediol, mapping onto a redundant set of pyridine-nucleotide-dependent oxidoreductases and a <i>pdu</i>-independent diol pathway. On kiwifruit, citrate accumulated 8.9-fold at 16 h and then declined, consistent with an intact <i>citCDEFG</i> citrate-lyase operon paired with absence of canonical oxidative tricarboxylic acid enzymes. The optimal extraction solvent was substrate-dependent, water for garlic and ethanol for onion and kiwifruit. Overall, these results show that substrate chemistry, rather than strain identity, dictates which genome-encoded pathways P7 engages, establishing P7 as a versatile, substrate-tunable platform for the functional fermentation and biorefining of furanic-rich substrate streams. Raw NMR data and ISA-Tab metadata are available via MetaboLights with identifier MTBLS14463.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":"198 11","pages":"8840 - 8863"},"PeriodicalIF":3.5,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954751","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":"Design of Multi-Epitope Cancer Vaccine Targeting p53 Tumor Antigen using Myotis lucifugus Sequencers: An Immunoinformatics Approach","authors":"Bhavin Maru,&nbsp;Ashish Shah,&nbsp;Ghanshyam Parmar,&nbsp;A. Rekha,&nbsp;Surya Nath Pandey","doi":"10.1007/s12010-026-05901-9","DOIUrl":"10.1007/s12010-026-05901-9","url":null,"abstract":"<div><p>The p53 tumor suppressor protein is dysregulated in more than 50% of human cancers, representing an attractive target for immunotherapy. However, immune tolerance to the self-antigen limits the effectiveness of traditional p53-based vaccines. The presented study is based on a comprehensive in silico approach to design a multi-epitope cancer vaccine using the p53 sequence from <i>Myotis </i><i>lucifugus</i> (little brown bat) that would break the self-tolerance without losing cross-reactive immunogenicity. Human and bat p53 amino acid sequences were aligned using claustral omega, with a highly conserved core domain at position 120–300 with 78.3% sequence identity as the vaccine region. Cytotoxic T-lymphocyte, helper T-lymphocyte, and B-cell epitopes were predicted using METMHCpan 4.1, NETMHCIIPan 4.0, and BepiPred 2.0, respectively, followed by immunological and safety screening, including antigenicity, allergenicity, toxicity, and human proteome homology analysis. Several epitopes meeting all criteria were assembled into a 134-amino acid construct with β-defensin-derived adjuvant and function-specific linkers. The vaccine demonstrated optimal physicochemical properties and strong structural integrity, with high Ramachandran favorable residues and Verify3D scores. Immune simulation showed sustained IgG1 response up to day 350, significant TH and CTL expansion, and pronounced TH1 polarization marked by IFN- γ levels. Population analysis reached 80.84% globally, with the highest representation in Europe and North America. Docking analysis showed strong binding to TLR4-MD2 and negligible interaction with wild-type and mutant p53, supporting immune-specific activity without off-target effects. Codon optimization yielded a CAI for E. coli expression. The designed multi-epitope vaccine demonstrated excellent immunogenic potential, favorable safety profiles, and broad population applicability.</p></div>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":"198 11","pages":"9360 - 9402"},"PeriodicalIF":3.5,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954753","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":"USP2-Mediated Deubiquitination of β-catenin Drives Colorectal Adenocarcinoma Progression and Immune Evasion.","authors":"Xiaoling Qian, Linhua Wang, Zhenfei Yu, Dandan Xiong, Jianming Zhou, Juan Zhang, Liqun Cui, Peng An","doi":"10.1007/s12010-026-05918-0","DOIUrl":"https://doi.org/10.1007/s12010-026-05918-0","url":null,"abstract":"<p><p>The deubiquitinase USP2 is implicated in multiple malignancies, yet its role in colorectal adenocarcinoma (COAD) remains undefined. USP2 expression in COAD was predicted using bioinformatic tools, and verified in clinical cohort of 30 paired COAD tumors and adjacent normal tissues. HCT-116 cells carrying either stable sh-USP2 knockdown or ectopic β-catenin overexpression were subjected to CCK-8 viability, colony-forming, Transwell invasion/migration, and cycloheximide (CHX) or MG132 pulse-chase assays, while co-immunoprecipitation (co-IP), reciprocal IP, ubiquitination immunoblots and confocal immunofluorescence were employed to map the USP2-β-catenin interaction. CD8⁺ T cells isolated from healthy donors were co-cultured with HCT-116 cells to assess cytotoxicity by LDH release. Finally, subcutaneous xenografts established in nude mice and syngeneic C57 mice were monitored for 28 days, after which tumors were excised, weighed, and analysed by immunohistochemistry for β-catenin and PD-L1 expression. USP2 was markedly up-regulated in COAD tissues and cell lines and associated with poor prognosis. USP2 directly bound and deubiquitinated β-catenin, prolonging its half-life and up-regulating PD-L1. USP2 knockdown suppressed proliferation, invasion, colony formation, and immune evasion, effects reversed by β-catenin re-expression. In vivo, USP2 silencing retarded tumor growth and reduced β-catenin and PD-L1 expression. USP2 stabilizes β-catenin to drive COAD progression and immune escape; targeting the USP2 - β-catenin axis offers a promising therapeutic strategy.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954781","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}