3 Biotech最新文献

The rising burden of diabetes, oxidative stress, and antimicrobial resistance underscores the need for safe, multifunctional therapeutics. This study explores the antioxidant, antidiabetic, antimicrobial, anti-inflammatory, and anti-biofilm properties of Silybum marianum (S. marianum) L. Gaertn. acetic acid extract, complemented by phytochemical profiling and molecular docking. The extract of S. marianum exhibited strong multifunctional bioactivity supported by in vitro and in silico analyses. Antioxidant evaluation (DPPH, ABTS, FRAP) revealed dose-dependent radical scavenging, achieving up to 92.5% inhibition at 1000 µg/mL and a high ferric-reducing capacity (105.6 µM Fe²⁺ equivalents). The extract significantly inhibited α-amylase and α-glucosidase, confirming its antidiabetic potential. In antimicrobial assays, notable activity was observed against Bacillus subtilis (15.2 mm) and Staphylococcus aureus (14.6 mm), with moderate effects on Gram-negative and fungal strains. The extract also showed over 85% inhibition of S. aureus biofilm formation, suggesting interference with quorum sensing and EPS matrix synthesis. Anti-inflammatory assays demonstrated up to 91.2% inhibition of protein denaturation and 86.7% red blood cell membrane stabilization, comparable to indomethacin. Macrophage-based cellular studies confirmed suppression of nitric oxide and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) with > 85% cell viability. GC-MS analysis identified major bioactives including D-arabinitol, chalcone derivatives, and isoquinoline compounds, which were strongly bound to key targets in docking studies-α-amylase, DNA gyrase, COX-2, and NADPH oxidase (binding energies - 9.0 to - 9.9 kcal/mol). These results collectively highlight S. marianum as a biocompatible source of multifunctional phytochemicals with antioxidant, antidiabetic, antimicrobial, anti-inflammatory, and anti-biofilm properties, supporting its potential for nutraceutical and therapeutic applications.

Spinal cord injury (SCI) causes severe functional impairments and involves both primary mechanical damage and secondary inflammation. Exosomes from human umbilical cord blood (HUCB) are emerging as promising therapies due to their bioactive components that regulate inflammation and support repair. Thirty-two male rats were randomly divided into four groups: Group A (laminectomy), Group B (contusion), Group C (contusion + PBS), and Group D (contusion + HUCB-exosomes). Contusion injuries were induced using the New York University (NYU) impactor method. HUCB-derived exosomes were extracted and confirmed using scanning electron microscopy (SEM), transmission electron microscopy (TEM), surface markers CD81 and CD9 via flowcytometry, along with dynamic light scattering (DLS), and zeta potential analysis. HUCB-exosomes were administered without prior in vitro expansion; 30 minutes' post-injury, Group D received 100 µg of HUCB-exosomes via tail vein injection for one week. Motor and behavioral functions were assessed using the Basso, Beattie, and Bresnahan (BBB) scale, narrow beam test (NBT), rotarod test, and open-field test. Western blotting was performed eight weeks' post-injury to analyze changes in inflammatory cytokines, and histological changes were assessed via H&E staining. HUCB-exosome administration significantly enhanced functional recovery in SCI rats, as evidenced by higher BBB scores, improved narrow beam, rotarod, and open-field performances compared with PBS and contusion groups. Histological analysis showed reduced cavity formation, increased neuronal density, and decreased gliosis in the exosome-treated group. Western blot results revealed marked downregulation of TNF-α, NLRP3, and GFAP expression. Additionally, exosome therapy restored antioxidant balance by reducing ROS and GSSG levels while elevating GSH, and immunohistochemistry confirmed reduced expression of apoptotic and autophagy markers. This study highlights the therapeutic potential of HUCB-derived exosomes in SCI, demonstrating their ability to attenuate inflammation and promote functional recovery. These findings support HUCB-exosomes as a promising, non-cell-based treatment strategy for SCI.

This study aimed to elucidate the molecular mechanism by which FBXW4 suppresses the progression of lung adenocarcinoma (LUAD). Functional experiments demonstrated that FBXW4 significantly inhibited LUAD cell proliferation, migration, and invasion, while promoting apoptosis. Furthermore, rescue experiments indicated that PKNOX2 silencing partially reversed the tumor-suppressive effects of FBXW4. Mechanistically, FBXW4 facilitated the ubiquitination and degradation of DNMT1, leading to a decrease of methylation of the PKNOX2 promoter. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays confirmed that PKNOX2 transcriptionally activated FHL1 by directly binding to its promoter. In addition, FHL1 was identified as a functional downstream effector responsible for mediating the inhibitory role of PKNOX2 in LUAD malignancy. These findings reveal a previously uncharacterized FBXW4/DNMT1/PKNOX2/FHL1 regulatory axis, providing mechanistic insight into LUAD suppression and potential therapeutic strategies.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04646-2.

A novel Streptomyces violaceoruber strain BM-41, isolated from shellfish aquaculture waste, demonstrated potent chitinolytic activity (2.362 U/mL). Whole-genome sequencing revealed a 7.83 Mb genome (72.6% GC) encoding 238 carbohydrate-active enzymes (CAZymes), with 75 glycoside hydrolases (GHs). Significantly, seven chitinase genes were identified: six GH18 family members (ChiA-ChiF) and one GH19 member (Chi2a), displaying greater genetic diversity than S. albidoflavus ATCC 27,414 (45 GHs). Fermentation optimization via single-factor experiments and Box-Behnken response surface methodology yielded optimal enzyme production conditions: 4.5% colloidal chitin, 7 g/L yeast extract, 0.3 g/L MgSO₄, pH 5.0, 30 ℃, and 30% medium volume. This enhanced chitinase activity 2.37-fold (from 0.995 to 2.362 U/mL). Enzymatic characterization showed optimal activity at pH 5.0 and 50 ℃, stability across pH 4-8, and ion-specific modulation: Mg²⁺ and K⁺ increased activity by 25-30%, whereas Cu²⁺ strongly inhibited catalysis. Genomic analysis uncovered a synergistic degradation pathway involving extracellular chitinases (ChiA-ChiF) and 10 key metabolic enzymes, including N-acetylglucosaminidases (EC 3.2.1.52), deacetylases (EC 3.5.1.25), and UDP-N-acetylglucosamine pyrophosphorylases (EC 2.7.7.23). This enzymatic network facilitates efficient conversion of chitin to N-acetylglucosamine monomers and downstream metabolites. The findings contribute to the understanding of S. violaceoruber BM-41 genomic features and its potential as a source of industrially relevant enzymes.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04634-6.

Hydroxynitrile lyases (HNLs) are stereoselective biocatalysts that catalyze the addition of hydrogen cyanide to carbonyl compounds, yielding enantiopure cyanohydrins-valuable intermediates in pharmaceutical and agrochemical synthesis. Recent advances have expanded our understanding of HNLs across multiple dimensions, including their evolutionary origins, structural diversity, and catalytic mechanisms. High-throughput screening methods have accelerated the discovery and functional assessment of novel HNLs from diverse biological sources, revealing enzymes from lipocalin, α + β barrel, and cupin superfamilies. Structural and mechanistic studies have elucidated active site architectures, enabling rational design and protein engineering for improved stability, substrate scope, and catalytic efficiency. Recombinant expression systems now support scalable production and purification, while immobilization techniques enhance enzyme reusability for industrial applications. HNLs have proven especially valuable in the asymmetric synthesis of cyanohydrins under mild, environmentally friendly conditions. This review highlights recent progress in HNL research, emphasizing innovations in enzyme discovery, engineering, and application, while outlining key challenges and future directions for integrating HNLs into sustainable biocatalytic processes.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04653-3.

Rice microbiome plays a critical role in the growth, health, stress tolerance, nutrient uptake, root development, and productivity of its host. In this study, advanced machine learning algorithms were applied to analyze the genomic data from 1365 rice-associated bacteria sourced from Bacterial and Viral Bioinformatics Resource Center (BV-BRC) database. After filtering, the genomic data of 280 organisms were selected and annotated to identify their respective genes. These were further categorized into ortholog groups, and based on the presence and absence of the ortholog groups, the organisms were clustered into eight groups. Genes encoding amino acid transport, inorganic ion transport and metabolism were the most common Clusters of Orthologous Genes (COG) categories observed across the various clusters while cellular process, biological regulation, and response to stimuli were the most common gene ontology terms. However, the presence of a large proportion of genes having unknown functions suggests the distribution of novel genes which could facilitate the functions including the plant colonization. Further to this, machine learning models were used to classify the organisms as either beneficial or pathogenic. Here, Support Vector Machine based analysis showed the highest accuracy (92.98%) when compared to the Logistic Regression (90.16%) and Random Forest (57.80%). From the analysis, ABC-type transporters such as ABC-type oligopeptide transport system were more abundantly distributed in beneficial bacteria. On the other hand, transposase such as Transposase InsA were observed to be common among pathogenic strains. From the results obtained, the presence of genes responsible for the nutrient transport and metabolic versatility was found to be significant for the beneficial bacteria, while the genetic variability was remarkable for the pathogens. The information generated in this study hence highlights the power of AI for predicting the beneficial interactions between the rice and its microbiome, and thereby offer its applications in enhancing the crop resilience and productivity for the sustainable agricultural practices.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04665-z.

Statins are widely used in the treatment of hyperlipidemia; however, their specific mechanisms of action remain incompletely understood. To identify key therapeutic targets, we integrated differential expression analysis with machine learning and identified IL27RA as a pivotal candidate. IL27RA expression was significantly upregulated in atorvastatin-treated hyperlipidemia patients compared to healthy controls but decreased following statin intervention. Functional enrichment analysis revealed its association with immune-related pathways, and consistent with this, immune infiltration analysis showed significant correlations between IL27RA expression and the abundance of Th1 and plasmacytoid dendritic cells. Molecular docking and dynamics simulations further confirmed stable binding between IL27RA and atorvastatin. Collectively, these results establish IL27RA as a key therapeutic target for statins in hyperlipidemia and highlight its role in modulating the immune microenvironment.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04668-w.

Angiogenesis plays a crucial role in cancer progression. However, the role of PARP1 in regulating chromatin remodelers and activating pro-angiogenic factors in cancer stem cells (CSCs) remains poorly understood. This study systematically investigates the detailed molecular mechanism through which PARP1 and its associated chromatin remodelers, P300 and GCN5, regulate angiogenesis in ex vivo patient-derived oral mucosa cancer stem cells (PD-OMCSCs). To investigate this mechanism, we used a combination of experimental approaches, including CAM assays, tube formation assays, biochemical analyses (western blot, gelatin zymography, and ELISA), molecular imaging (tissue immunofluorescence), and protein-protein interaction (co-immunoprecipitation and in silico study). Comparative analyses revealed significantly higher expression of PARP1, P300, and GCN5 in oral cancer tissues compared to normal ones. Co-immunoprecipitation and docking studies confirmed their mutual interactions, forming a chromatin-remodeling complex (PARP1-P300-GCN5) that facilitates angiogenic gene activation and expression. Quinacrine (QC), in combination with PARP inhibitor Talazoparib, disrupted this complex, leading to significant downregulation of VEGFA expression, reduced MMP activity, and suppression of angiogenic markers (Ang-1, Ang-2, TGF-β, CXCL-12, VEGFC, HIF-1α, and IL-6). These effects collectively impaired endothelial cell tube formation and blood vessel development in both HUVECs and CAM models. Furthermore, individual knockdown of PARP1, P300, or GCN5 reduced VEGFA expression, indicating their important role in regulating tumor angiogenesis. In conclusion, the QC and Talazoparib combination effectively prevents the activation and secretion of angiogenic factors, thereby suppressing angiogenesis, and may serve as a promising therapeutic approach for oral cancer by targeting PARP1 and associated chromatin remodelers.

This investigation was intended to prepare lipid-polymer hybrid nanoparticles (LPHNPs) that are laden with Gemcitabine hydrochloride (GEM) for the controlled delivery to treat Hepatocellular carcinoma (HCC). LPHNPs were developed by the solvent evaporation technique employing polycaprolactone (PCL) as the biodegradable polymeric core and a phospholipid shell comprised of soya phosphatidylcholine (SPC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE). This study presents a cost-effective, simple method for functionalizing LPHNPs with the carbohydrate ligand D-galactose (GA) using stearyl amine (SA) as a linker. To examine the impact of three independent factors on the particle size, percent entrapment efficiency (% EE), and percent drug loading (% DL), a three-factor, three-level Box-Behnken design (BBD) was implemented with Design-Expert 13 software. The nanoparticles' size range increased from 194.1 to 505.3 nm when the polymer content increased. GEM's percent drug release profile in the galactose functionalized gemcitabine-loaded lipid-polymer hybrid nanoparticles (GEM-LPHNPs-GA) suggests they are appropriate candidates for targeting the tumors microenvironment. In vitro drug release tests revealed a higher GEM release at pH 5.5 compared to the physiological pH of 7.4 for 48 h. Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (¹H-NMR) spectroscopy verified that the conjugate GA-SA imine bond formed. The cytotoxicity of GEM-LPHNPs-GA was significantly greater than that of GEM-LPHNPs or GEM alone, as evidenced by the MTT assay conducted on HepG2 cells. Throughout the incubation period, HepG2 cells exhibit a markedly higher absorption of dye-loaded LPHNPs-GA than LPHNPs. GEM-LPHNPs-GA is an efficacious formulation for the targeted administration of anti-cancer therapeutics.

Petroleum refinery wastewater (PRWW) with 4% salinity was subjected to treatment and simultaneous generation of energy in air cathode-microbial fuel cell (MFC). Substrate load (SL) such as 0.41 gCOD/L, 0.84 gCOD/L, 1.26 gCOD/L, 1.78 gCOD/L and 2.25 gCOD/L was trialed in air cathode MFC. COD (chemical oxygen demand) reduction was 88% (total COD) and 87% (soluble COD) at optimized SL of 1.78 gCOD/L. Corresponding power and current density derived at optimized SL of 1.78 gCOD/L was 879 mW/m² and 1052 mA/m² respectively. Degradation of low and high molecular weight petroleum hydrocarbons in the PRWW was greater than 90% to 100%  and 71% to 82% respectively. Supplementation with a mild nutritional substrate in PRWW accelerated the hydrocarbon biodegradation with time reduction in MFC operated at 1.78 gCOD/L SL. Phylogenetic analysis revealed the dominancy of exo-electrogenic halophilic strains such as Ochrobactrum, Marinobacter, Bacillus and Stenotrophomonas in the reactor. Thus the bioaugmentation of halophiles in MFC efficiently treated PRWW and harvested bioenergy under saline condition.