Samah H. Abu-Hussien, Muhammad A. Khan, Ahmed Othman Alsabih, Abdulaziz Alamri, Mostafa A. Abdel-Maksoud, Mohammed Aufy, Salem S. Salem, Moustafa A. A. Hassan
{"title":"Box–Behnken-Optimized Bacterial Nanocellulose–Silver and Zinc Oxide Nanocomposites: Bactericidal Activity, Antioxidant Capacity, Cytotoxicity, and In vitro Wound Healing Assessment","authors":"Samah H. Abu-Hussien, Muhammad A. Khan, Ahmed Othman Alsabih, Abdulaziz Alamri, Mostafa A. Abdel-Maksoud, Mohammed Aufy, Salem S. Salem, Moustafa A. A. Hassan","doi":"10.1007/s12010-026-05853-0","DOIUrl":"10.1007/s12010-026-05853-0","url":null,"abstract":"<div><p>Bacterial nanocellulose (BNC) nanocomposites functionalized with silver (BNC-AgNC) and zinc oxide (BNC-ZnONC) nanoparticles were developed and optimized using Box-Behnken design (BBD) for potential wound dressing applications. Quadratic models exhibited excellent predictability (R² = 0.9765 and 0.9811, respectively), identifying optimal loading conditions of 3% nanoparticle concentration, 4 h loading time, and 32.5 °C, yielding maximum inhibition zone diameters of 2.81 cm (BNC-AgNC) and 2.65 cm (BNC-ZnONC). Nanocomposite formation was confirmed by UV-Vis spectroscopy, XRD, FTIR, SEM-EDX, DLS, and TGA, collectively demonstrating successful nanoparticle incorporation without disruption of the cellulose crystalline backbone. Both composites exhibited pronounced antibacterial activity against Gram-positive (<i>S. aureus</i>, <i>S. pyogenes</i>) and Gram-negative (<i>S. marcescens</i>, <i>P. aeruginosa</i>) pathogens, with BNC-AgNC showing bactericidal potency (MIC: 8–32 µg/mL) compared to BNC-ZnONC (MIC: 32–128 µg/mL). Cytotoxicity assessment on human fibroblasts revealed that BNC-ZnONC maintained > 97% cell viability across all tested concentrations (IC₅₀ >125 µg/mL), whereas BNC-AgNC exhibited concentration-dependent toxicity (IC₅₀ =63 µg/mL). Scratch wound healing assays demonstrated that BNC-ZnONC promoted fibroblast migration comparable to pristine BNC (81.84% closure), while BNC-AgNC significantly impaired wound closure even at sub-lethal concentrations. DPPH radical scavenging and hydration studies further supported the biocompatibility profile of BNC-ZnONC. These findings establish a functional dichotomy: BNC-AgNC offers potent bactericidal activity with a narrow therapeutic window, while BNC-ZnONC represents a more favorable candidate combining antimicrobial efficacy, cytocompatibility, and pro-healing properties for biomedical wound management.</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":"9118 - 9151"},"PeriodicalIF":3.5,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617842","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}
Wen-Jing Feng, Can Qin, Ming-Shu Zhang, Zi-Yang Luo, Bang-Wei Chen, Lei Wu, Fu-Gen Zhang, Jun-Jin Deng, Xiao-Chun Luo
{"title":"Seeking soil microbial degraders and enzymatic genes for efficient biomass recycling","authors":"Wen-Jing Feng, Can Qin, Ming-Shu Zhang, Zi-Yang Luo, Bang-Wei Chen, Lei Wu, Fu-Gen Zhang, Jun-Jin Deng, Xiao-Chun Luo","doi":"10.1007/s12010-026-05859-8","DOIUrl":"10.1007/s12010-026-05859-8","url":null,"abstract":"<div><p>Biodegradation is the most sustainable biomass recycling strategy, yet the absence of efficient microbial degraders remains a critical bottleneck. While soil microorganisms can decompose diverse biomass, their functional specificity for distinct agricultural by-products remains inadequately characterized. To address this, five agricultural by-products, including fish skin, soybean meal, shrimp shell, corn straw and chicken feather, were individually or combinatorially incubated in soil. Comparative analysis of 16 S rRNA amplicons and metagenomics from actively degrading microbial communities versus native soil identified key functional degraders. Declines in Chao1 and Shannon indices within biomass-amended soil groups indicated community simplification, driven by the dominance of novel utilizers over indigenous taxa. Genera enriched in native soil were replaced by divergent taxa across biomass types, revealing substrate-dependent community succession. LEfSe analysis identified biomass-specific utilizers at multiple taxonomic levels. Co-occurrence network analysis showed strong positive co-occurrence patterns between significantly enriched operational taxonomic units (OTUs), suggesting potential co-occurrence patterns and shared responses to biomass amendment. FAPROTAX revealed enhanced C/N/S metabolism during biomass utilization. Metagenomic screening identified markedly higher numbers of biomass-degradation genes encoding hydrolases (e.g., proteases, cellulases, chitinases), consistent with significantly elevated enzyme activities in amended soils compared to undetectable levels in controls. Among six candidate OTUs substantially enriched in chicken feather-amended soil, three species demonstrated efficient feather degradation, with some exhibiting multi-substrate capability. This study elucidates substrate-dependent biomass cycling in soil and provides candidate degraders, including <i>Vicinamibacterales</i>-related OTUs, unclassified <i>Enterobacteriaceae</i>, <i>Sphingobacterium paludis</i>, <i>Sphingobacterium griseoflavum</i>, and <i>Lysinibacillus mangiferihumi</i>, as well as enzymatic gene resources for engineered biomass recycling.</p></div>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":"198 11","pages":"9066 - 9092"},"PeriodicalIF":3.5,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617806","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":"Synergistic Degradation of Parabens via Laccase/TEMPO/Cutinase System: Performance and Mechanism.","authors":"Juncheng Hu, Leqi Yang, Ruofei Zhu, Dan Wang","doi":"10.1007/s12010-026-05854-z","DOIUrl":"https://doi.org/10.1007/s12010-026-05854-z","url":null,"abstract":"<p><p>To develop a green enzymatic method for the remediation of parabens (PBs) contaminants, a ternary composite system comprising laccase, 2, 2, 6, 6-tetramethylpiperidine-1-oxyl (TEMPO) mediator, and cutinase SE50 (LCTM) was constructed. Using methylparaben (MP) as a model substrate, the degradation performance, kinetic characteristics, and underlying mechanisms of the system were systematically investigated. The results demonstrated that TEMPO significantly enhanced the catalytic conversion of MP by laccase, and the subsequent introduction of cutinase SE50 further boosted the overall degradation efficiency. Under the optimized conditions (0.5 U/mL cutinase SE50, 1.2 U/mL laccase, 25 mg/L TEMPO, temperature 50 °C, and pH 6.0), the degradation rate of MP reached 96.8% within 24 h. The degradation process well conformed to a pseudo-first-order kinetic model with an apparent reaction rate constant of 191.84 × 10⁻³ h⁻¹. Subsequently, identification of the degradation products revealed that MP was initially hydrolyzed into p-hydroxybenzoic acid, and then underwent decarboxylation and pivotal hydroxylation to generate the core intermediate catechol. Catechol then underwent oxidative ring-cleavage into small-molecule organic acids, including succinic, pyruvic, and glycolic acids, which were ultimately mineralized. Furthermore, the effects of different PBs structures on degradation efficiency were investigated, with higher degradation efficiency observed for short-chain substrates possessing lower steric hindrance. This study validates the potential application of the LCTM system in the remediation of ester-based pollutants and provides a theoretical basis for composite enzymatic degradation mechanisms.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597368","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}
Sayed M S Abo El-Souad, Marwa Sharaky, Marwa A Ramadan, Jehane I Eid, Mona M Soliman
{"title":"Biosynthesis of Silver and Gold Nanoparticles using Inonotus obliquus: A strategy for Antimicrobial, Antioxidant and Cytotoxic Applications.","authors":"Sayed M S Abo El-Souad, Marwa Sharaky, Marwa A Ramadan, Jehane I Eid, Mona M Soliman","doi":"10.1007/s12010-026-05847-y","DOIUrl":"https://doi.org/10.1007/s12010-026-05847-y","url":null,"abstract":"<p><p>The development of safer and greener routes to bioactive metal nanomaterials remains an active area of research. In this study, we report the one-pot synthesis of gold (Au@Chaga) and silver (Ag@Chaga) nanoparticles using the ethyl acetate fraction of Inonotus obliquus (Chaga) as a dual reductant and capping agent. The nanoparticles, characterized by TEM, showed uniform sizes of 26 ± 3 nm (Au@Chaga) and 12 ± 3 nm (Ag@Chaga). Ag@Chaga NPs showed a larger inhibition zone against Staphylococcus aureus (25 ± 3.0 mm), followed by Salmonella typhimurium (18 ± 1 mm) with MICs of 12.5 to 25 µg/mL. Au@Chaga yielded inhibition-zone diameters ranging from 12.7 ± 0.58 to 17.67 ± 2.08 mm, with MICs of 12.5 to 25 µg/mL. Anticancer activity was evaluated across 18 human cancer cell lines using SRB/MTT assays. Preliminary biocompatibility was assessed by parallel viability testing in non-tumorigenic human cells, including olfactory epithelial cells (OEC) and human skin fibroblasts (HSF). Au@Chaga generally showed broader antiproliferative activity than Ag@Chaga across several cancer cell lines, although responses varied among cancer and non-malignant cells. These findings highlight the need for formal calculation of the selectivity index and an extended biosafety assessment. The nanoparticles exhibited differential cytotoxic responses between cancerous and non-cancerous cells, highlighting the need for future studies to establish formal selectivity indices. Genotoxicity (Comet assay), oxidative and nitrosative stress markers, and antioxidant enzyme activities collectively suggest that redox perturbation contributes to the observed cellular responses. Overall, this study provides proof of concept that Chaga-mediated Au/Ag nanoparticles can be produced via a biogenic protocol and exhibit measurable in vitro antibacterial and anticancer activities within the stated scope. Extension to multidrug-resistant clinical isolates and quantitative selectivity analyses will be required to substantiate translational claims.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597323","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}
Surendra Kumar Gautam, Biswaranjan Paital, Hasan Abdulameer Abbas Alsaffar
{"title":"Marine-Derived Nanocarriers for Immunomodulatory Drug Delivery: a Review On Convergence of Marine Pharmacology and Nanotechnology.","authors":"Surendra Kumar Gautam, Biswaranjan Paital, Hasan Abdulameer Abbas Alsaffar","doi":"10.1007/s12010-026-05830-7","DOIUrl":"https://doi.org/10.1007/s12010-026-05830-7","url":null,"abstract":"<p><p>Marine-derived nanocarriers represent an emerging interface between marine pharmacology and nanotechnology for immunomodulatory drug delivery. The marine ecosystem provides diverse bioactive compounds, such as polysaccharides, peptides, lipids, proteins, and alkaloids, many of which possess inherent immunoregulatory activity. When incorporated into nanoscale delivery systems such as polymeric nanoparticles, liposomes, micelles, hydrogels, and exosome-like vesicles, these bioactive compounds may exhibit improved stability, bioavailability, controlled release, and targeting efficiency. This review summarizes major classes of marine-derived nanocarriers and discusses their immunomodulatory mechanisms, including pattern recognition receptor activation, oxidative stress modulation, macrophage polarization, dendritic cell maturation, cytokine regulation, and intracellular signaling pathways. Their applications in autoimmune disorders, infectious diseases, vaccine delivery, and cancer immunotherapy are also reviewed. Despite promising preclinical evidence, clinical translation remains limited by challenges related to scalable production, batch-to-batch reproducibility, long-term stability, tissue-specific targeting, safety evaluation, and regulatory approval. Overall, marine-derived nanocarriers offer promising platforms for immunomodulatory drug delivery, but further mechanistic, comparative, and translational studies are required to establish their clinical relevance.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590109","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}
Ding Zhang, Ruxia Li, Xue Fang, Zeliang Chen, Jiahai Lu
{"title":"Computational Design of a Broad-Spectrum Multi-Epitope mRNA Vaccine Candidate for Mammarenaviruses.","authors":"Ding Zhang, Ruxia Li, Xue Fang, Zeliang Chen, Jiahai Lu","doi":"10.1007/s12010-026-05832-5","DOIUrl":"https://doi.org/10.1007/s12010-026-05832-5","url":null,"abstract":"<p><p>Mammarenaviruses cause serious diseases such as Lassa fever and Argentine hemorrhagic fever that threaten global public health; however, vaccines and therapeutic options remain limited. Therefore, developing a broadly effective vaccine against mammarenaviruses is a priority. In this study, we systematically analyzed the main structural protein sequences of ten mammarenaviruses. We combined antigenic epitopes from the Immune Epitope Database (IEDB) and used inverse vaccination and immunoinformatics methods to screen for highly conserved B- and T-cell epitopes with strong immunogenicity. We then added tissue plasminogen activator (tPA), which is the most effective vaccine against these pathogens. To construct a broad-spectrum multi-epitope fusion mRNA vaccine candidate, we included a tPA signal peptide, PADRE adjuvant, and linkers. The mRNA sequences were algorithm-optimized. We assessed the structural stability and immunogenicity of the candidate vaccine using molecular docking, molecular dynamics (MD) simulation, and immunosimulation. The designed vaccine had good antigenicity and structural stability, forming stable complexes with a variety of intrinsic immunoreceptors and triggering a strong, sustained, and comprehensive immune response during immunosimulation. Our study findings posit the designed vaccine as a potential broad-spectrum multi-epitope vaccine candidate against mammarenaviruses. Further real-world studies are required to validate these results.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590114","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":"Biosynthesis of Silver Nanoparticles Using Brevibacillus parabrevis OW4: Optimization, Characterization, Antibacterial and Antibiofilm Applications.","authors":"Hamza Ettadili, Caner Vural","doi":"10.1007/s12010-026-05840-5","DOIUrl":"https://doi.org/10.1007/s12010-026-05840-5","url":null,"abstract":"<p><p>The biosynthesis of silver nanoparticles (AgNPs) using eco-friendly approaches has emerged as an important area of research in nanobiotechnology. In this study, a sustainable approach for the green synthesis of AgNPs was investigated using silver nitrate (AgNO<sub>3</sub>) as a precursor and Brevibacillus parabrevis OW4 as an eco-friendly reducing and capping agent. Microbial-mediated AgNPs synthesis was carried out using a bacterial cell-free filtrate (CFF). Optimal synthesis conditions were established at pH 11, 2 mM AgNO<sub>3</sub>, and 72 h of incubation. Physicochemical characterization confirmed the formation of crystalline, spherical, polydisperse AgNPs with a surface plasmon resonance (SPR) peak at 400-440 nm and an average size of 58 ± 19 nm. The antibacterial and antibiofilm activities of the biogenic AgNPs were evaluated against Escherichia coli ATCC 10536, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 33862, and Enterococcus faecalis ATCC 19433. The results demonstrated that the biogenic AgNPs could effectively inhibit representative Gram-negative and Gram-positive human pathogens. The minimum inhibitory concentration (MIC) ranged from 7.8 ± 0.0 µg/mL to 31.2 ± 0.0 µg/mL, and the minimum bactericidal concentration (MBC) for all strains was 62.5 ± 0.0 µg/mL. Furthermore, this concentration was able to reduce more than 50% (p < 0.001) of biofilm formation, while 125 ± 0.0 µg/mL resulted in over 90% (p < 0.001) of biofilm formation inhibition in the tested strains. These findings demonstrate that B. parabrevis OW4-mediated AgNPs represent a promising, sustainable, and effective antimicrobial strategy. To the best of our knowledge, this study is the first to report the synthesis of AgNPs using B. parabrevis OW4, further emphasizing its novelty. The strong antibacterial and antibiofilm activities highlight their potential applications in combating biofilm-associated infections and support further investigation into their biomedical use.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576658","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":"Decoding Antimicrobial Activities of Peppermint (Mentha Piperita), Tea Tree (Melaleuca Alternifolia), and Eucalyptus (Eucalyptus Globulus) Essential Oils: In Silico and In Vitro Approaches.","authors":"Sema Zabcı, İpek Zeynep Durusu, Aliye Ezgi Güleç Taşkıran","doi":"10.1007/s12010-026-05841-4","DOIUrl":"https://doi.org/10.1007/s12010-026-05841-4","url":null,"abstract":"<p><p>Essential oils are popular for their antimicrobial properties. In the present study, the antibacterial activities of peppermint (Mentha piperita), tea tree (Melaleuca alternifolia) and eucalyptus (Eucalyptus globulus) essential oils were evaluated using both in vitro and in silico approaches. The activities were tested against both Escherichia coli and Staphylococcus aureus using disc diffusion analysis, minimum inhibitory concentration, and minimum bactericidal concentration assays. Furthermore, the interaction of the selected essential oil's major constituents, including terpinen-4-ol, menthol, and 1,8-cineole, with the highly conserved ribosomal protein uS12 was identified by molecular docking analysis. Peppermint oil showed the highest activity and selective efficacy toward Staphylococcus aureus, while tea tree oil was more effective against Escherichia coli. Molecular docking results revealed that major constituents like menthol and terpinen-4-ol could mimic gentamicin's binding profile, specifically destabilizing the uS12 N-terminal domain and Arg86 to impair translational accuracy which might be resulted in antimicrobial activity through translation inhibition. The results provide a structural basis for these essential oils as potent natural inhibitors of bacterial protein synthesis.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576714","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}
Waqas Ali, Muhammad Ali, Misbah Sehar, Soha Shahid, Yow-Ling Shiue, Ghulam Mustafa, Bushra Akhtar, Ali Sharif
{"title":"Antidiabetic Effect of Coronopus Didymus, Azadirachta Indica and Their Active Compound Quercetin Against STZ-NA Induced Diabetes Mice Models","authors":"Waqas Ali, Muhammad Ali, Misbah Sehar, Soha Shahid, Yow-Ling Shiue, Ghulam Mustafa, Bushra Akhtar, Ali Sharif","doi":"10.1007/s12010-026-05851-2","DOIUrl":"10.1007/s12010-026-05851-2","url":null,"abstract":"<div><p><i>Coronopus didymus</i> (Brassicaceae) is a medicinal herb valued for its anti-inflammatory and hyperlipidemic properties; however, its antidiabetic potential remains entirely unexplored. Furthermore, despite the known therapeutic benefits of <i>Azadirachta indica</i> and the bioflavonoid quercetin, their evaluation in combination with <i>C. didymus</i> has never been investigated. To address this knowledge gap, this study pioneers the evaluation of <i>C. didymus</i>,<i> A. indica</i>, and quercetin—individually and as a novel combined formulation for the management of type 2 diabetes mellitus (T2DM). We employed an integrated approach utilizing in silico network pharmacology and molecular docking (targeting NOS3, AKT1, and PPARG), in vitro bioassays (antioxidant, α-amylase inhibition, hemolytic, and anticancer), and in vivo evaluation in streptozotocin-nicotinamide (STZ-NA)-induced diabetic mice. Network screening identified 100 overlapping targets between the quercetin and T2DM, prioritizing 15 key hub targets via protein-protein interaction and KEGG pathway enrichment analyses. Molecular docking confirmed strong binding affinities of the lead compounds to NOS3, AKT1, and PPARG. In vitro assays validated robust antioxidant, α-amylase inhibitory, and anticancer activities, while maintaining a safe hemolytic profile. In vivo trials demonstrated that while individual treatments effectively lowered blood glucose, the combined formulation exhibited superior hepatoprotective efficacy, profoundly reducing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (<i>p</i> < 0.0001) toward baseline control levels compared to individual plant extracts, alongside enhancing serum antioxidants and ameliorating histopathological damage in hepatic and intestinal tissues. In conclusion, this study bridges a critical gap in ethnopharmacology by identifying the antidiabetic potential of <i>C. didymus</i> and demonstrating that its combination with <i>A. indica</i> and quercetin offers a potent, distinct hepatoprotective advantage, highlighting its potential as a targeted nutraceutical approach for managing T2DM and its associated hepatic complications.</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":"8482 - 8507"},"PeriodicalIF":3.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576651","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":"Aflatoxin B1 Induces Anxiety-related Neurotoxicity Through Brain-region-Specific EGFR/AKT Signaling: Evidence from Integrative Network Toxicology and Mendelian Randomization","authors":"Tingting Chen, Jiang Du, Liping Bu, Long Jiao","doi":"10.1007/s12010-026-05844-1","DOIUrl":"10.1007/s12010-026-05844-1","url":null,"abstract":"<div><p>Aflatoxin B1 (AFB1) is a widespread foodborne mycotoxin with well-established hepatotoxic and carcinogenic effects; however, its potential role in neuropsychiatric disorders remains unclear. Emerging evidence suggests that AFB1 can cross the blood-brain barrier, inducing oxidative stress and neuronal dysfunction. Whether these alterations contribute to anxiety-related molecular changes in the human brain remains poorly understood. An integrative approach combining network toxicology, brain-region-specific two-sample Mendelian randomization (MR), molecular docking, and experimental validation was employed. AFB1-associated targets were identified via STITCH, ChEMBL, and SwissTargetPrediction, and intersected with anxiety-related genes from GeneCards and GSEA. Protein–protein interaction (PPI) analysis, topological screening, and functional enrichment were used to identify hub genes and key pathways. MR analysis utilized cortex and cerebellum expression quantitative trait loci (eQTL) data from GTEx v8. Molecular docking evaluated binding interactions between AFB1 and key proteins. SH-SY5Y cells were used to validate alterations in oxidative stress and signaling. A total of 196 shared targets were identified, and 24 hub genes were screened based on the intersection of the top 40 genes ranked by degree, betweenness, and closeness centrality analyses. Enrichment analysis highlighted oxidative stress, apoptosis, MAPK, PI3K-Akt signaling, and monoaminergic synaptic pathways. MR analysis revealed region-specific associations: cortical EGFR expression positively correlated with anxiety risk, while cerebellar PPARG expression exhibited a protective effect. Additional genes (AKT1, KRAS, ABL1, PRKACB) showed positive cerebellar associations. Docking analysis indicated stable binding between AFB1 and key proteins. Experimental validation confirmed increased EGFR and AKT1 expression, reduced PPARG expression, and elevated ROS levels in SH-SY5Y cells. AFB1 promotes anxiety-related neurotoxicity in a brain-region-specific manner, supported by Mendelian randomization evidence, by inducing oxidative stress, disrupting EGFR/AKT signaling, and suppressing PPARG-mediated neuroprotection. These findings elucidate a mechanistic link between AFB1 exposure and neuropsychiatric risk, and highlight the need for stricter food safety regulation and incorporation of mycotoxin exposure into anxiety risk assessment and prevention strategies.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>Graphical Abstract: Region-specific molecular mechanisms linking Aflatoxin B1 exposure to anxiety disorder risk. Integration of Mendelian randomization, molecular docking, and network toxicology reveals that AFB1 may increase anxiety risk by targeting EGFR in the cortex while suppressing the protective effects of PPARG in the cerebellum, mediated by oxidative stress and cell-survival signaling pathways</p></div></div></figure><","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":"198 11","pages":"8709 - 8729"},"PeriodicalIF":3.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576687","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}