BMC Biotechnology最新文献

{"title":"Unveiling a putative class 3 L-asparaginase in Glutamicibacter sp.: from soil isolation to in silico characterization.","authors":"Mahdis Mofidi, Gholamhossein Ebrahimipour, Maryam Azimzadeh Irani, Ali Etemadi, Mohammad Yaghoubi-Avini","doi":"10.1186/s12896-026-01179-1","DOIUrl":"10.1186/s12896-026-01179-1","url":null,"abstract":"<p><strong>Background: </strong>Type II L-asparaginases are important therapeutic agents for treating childhood leukemia, but numerous side effects of these enzymes, besides neutralization by antibodies due to repeated injection, prompt extensive research to identify alternatives in other classes of this enzyme.</p><p><strong>Results: </strong>Among the six asparaginase-producing strains, the best-producing isolate was identified as Glutamicibacter. The asparaginase and glutaminase activities in culture supernatant were 15 U/ml and 1.5 U/ml, respectively. The full-length asparaginase gene was sequenced, and the phylogenetic tree revealed strong clustering with recently identified class 3 asparaginases from Rhizobium etli. The presence of key residues from Class 3 ReAV and ReAIV further confirms this similarity. The AlphaFold 3 server confidently predicted the enzyme's 3D structure. Molecular docking of L-asparagine and L-glutamine using Rosetta revealed binding energies of -9.99 REU for both substrates that were higher than those of the Type IV and V enzymes. Molecular dynamics results indicated that enzyme-Asn was more stable than enzyme-Gln with average RMSD values of 0.33 nm and 0.44 nm, respectively. Enzyme-Asn reached a relatively stable plateau after 0.05 ns, whereas enzyme-Gln showed a sudden jump after 0.75 ns, indicating the separation of glutamine from the protein. A comparison of the antigenic determinants of GlAVI with those of ReAIV, ReAV, EcAII, and ErAII revealed that GlAVI exhibited lower immunogenicity than the other enzymes. Allergenic epitopes were predicted using bioinformatics, demonstrating that nonallergenic epitopes cover a significant portion of the enzyme.</p><p><strong>Conclusion: </strong>The newly isolated Glutamicibacter L-asparaginase appears to be a new type of class 3 asparaginases with high potential for novel therapeutic drug development because of its less and dissimilar immunological properties.</p>","PeriodicalId":8905,"journal":{"name":"BMC Biotechnology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a comprehensive in vitro organ model for androgenetic alopecia.","authors":"Shizhao Liu, Wenzhen Li, Botian Jiang, Haoyang Li, Jian Chen, Zhexiang Fan, Zhiqi Hu, Qian Qu, Yong Miao","doi":"10.1186/s12896-026-01176-4","DOIUrl":"10.1186/s12896-026-01176-4","url":null,"abstract":"<p><strong>Background: </strong>Male androgenetic alopecia (AGA) is the most common hair loss disorder. However, research on AGA remains limited, primarily due to the lack of clinical samples and imperfect AGA models incapable of replicating the androgen sensitivity of AGA.</p><p><strong>Methods: </strong>An AGA organ model was established by optimizing the concentration of dihydrotestosterone (DHT) and simulating AGA pathology through organotypic culture. The model's effectiveness was evaluated using histology, immunohistochemistry, and RNA-seq analysis, focusing on hair follicle (HF) growth, proliferation, apoptosis, key signaling molecules in AGA, stem cell state, and androgen receptor (AR) alterations.</p><p><strong>Results: </strong>We determined the optimal DHT concentration for our AGA organ model at 5 × 10^- 6 mol/L. The model demonstrated inhibited HF growth and accelerated entry into the catagen phase, with a 24% reduction in matrix cell proliferation and a 31% increase in apoptosis. Key molecular changes included decreased β-catenin and IGF-1 expression and elevated TGF-β1, DKK1, p21, and AR levels. The expression of the dermal papilla (DP) cell marker versican was reduced, while the follicular stem cell marker K15 remained unchanged. Moreover, the model successfully replicated the partial reversal of DHT's effects by minoxidil or AR antagonist bicalutamide. RNA-seq analysis revealed alterations in the Wnt/β-catenin and TGF-β signaling pathways and inflammatory responses in the AGA model.</p><p><strong>Conclusions: </strong>Our study presents a novel human in vitro AGA model that closely mirrors the clinical features of AGA in terms of morphology and molecular pathology. Beyond mechanistic research, this model provides a translationally relevant platform for drug evaluation and personalized therapeutic development. By preserving native androgen sensitivity and pathological microenvironment, this work lays a foundation for discovering new regenerative treatments for AGA.</p>","PeriodicalId":8905,"journal":{"name":"BMC Biotechnology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13274076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoinformatics-guided design of a multi-epitope vaccine targeting WISP1 for gastric cancer.","authors":"Negar Mottaghi-Dastjerdi, Behzad Shahbazi, Khadijeh Ahmadi, Mohammad Soltany-Rezaee-Rad","doi":"10.1186/s12896-026-01154-w","DOIUrl":"10.1186/s12896-026-01154-w","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer remains a leading cause of cancer-related mortality worldwide, and effective preventive or therapeutic vaccines are still lacking. WNT1‑inducible signalling pathway protein 1 (WISP1/CCN4) is a secreted matricellular protein that is overexpressed in gastric tumours and associated with poor prognosis, making it a promising immunotherapy target. We aimed to design a multi‑epitope protein vaccine candidate targeting WISP1 using an immunoinformatics workflow.</p><p><strong>Results: </strong>We predicted linear B‑cell epitopes from WISP1 and filtered them for antigenicity, non-allergenicity, and non-toxicity. High‑scoring MHC class I and class II T‑cell epitopes with broad HLA coverage were then selected. The final construct combined validated B‑ and T‑cell epitopes with appropriate linkers and a TLR‑agonist adjuvant to enhance immunogenicity. Physicochemical profiling indicated that the construct is stable, soluble, hydrophilic and antigenic, with no predicted allergenicity or toxicity. Secondary and tertiary structures were modelled, refined and validated, revealing proper folding and favourable stereochemical quality. Molecular docking showed strong binding to innate immune receptors, particularly TLR4, and molecular dynamics simulations confirmed stable receptor-vaccine interactions with low structural deviation. Binding‑free energy analysis further supported these results. Immune simulations predicted robust primary and secondary immune responses characterised by sustained IgG/IgM production, increased IFN‑γ and IL‑2, and activation of memory B and T cells. Codon optimisation and in‑silico cloning suggested feasibility for experimental expression.</p><p><strong>Conclusions: </strong>These results indicate that the proposed WISP1 multi‑epitope vaccine is antigenic, safe, structurally stable and capable of eliciting broad humoral and cellular immune responses in silico. This work provides a testable candidate for experimental validation and highlights secreted CCN family proteins as novel targets for gastric cancer vaccines.</p>","PeriodicalId":8905,"journal":{"name":"BMC Biotechnology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modified langendorff-free method for isolating cardiomyocytes and non-cardiomyocytes from adult mice.","authors":"Runhua Li, Jia Shen, Shuang Li, Yingchao Shi, Wenting Zhao, Chenqiu Wang, Lu Chen, Jiamian Chen, Xiaolei Cheng, Junyue Xing, Zhen Li, Tongguang Shi, Chuanyu Gao, Hao Tang, Liguo Jian, Dongdong Jian, Datun Qi","doi":"10.1186/s12896-026-01174-6","DOIUrl":"10.1186/s12896-026-01174-6","url":null,"abstract":"<p><strong>Background: </strong>Adult murine cardiomyocytes serve as a pivotal model for cardiovascular research. High-quality isolation is essential for studying disease mechanisms and drug screening. Current methods, however, are limited by reliance on specialized equipment and inconsistent efficiency, necessitating a more convenient and reliable protocol.</p><p><strong>Methods and results: </strong>We developed an optimized, Langendorff-free method for isolating cardiomyocytes and cardiac fibroblasts from adult mice. Following anesthesia, an enzymatic digestion solution was infused directly via the aortic root, utilizing the coronary circulation to achieve efficient tissue dissociation. This approach yielded adult mouse cardiomyocytes with high viability, intact morphology, and suitability for long-term culture, comparable to the standard Langendorff technique. Functionally, the isolated cardiomyocytes retained robust responsiveness to pathological stimuli, including hypoxia and adrenergic agonists (isoprenaline, norepinephrine, phenylephrine), demonstrated by characteristic alterations in contractile function, relaxation kinetics, and calcium handling. Furthermore, cardiac fibroblasts co-isolated using this protocol could be successfully activated by TGF-β, showing significant upregulation of myofibroblast markers (e.g., α-smooth muscle actin) and pro-fibrotic signaling pathways.</p><p><strong>Conclusion: </strong>This study establishes a novel, efficient, and accessible method for the simultaneous isolation of functional cardiomyocytes and cardiac fibroblasts from adult mice. The protocol overcomes key limitations of existing techniques and provides a reliable platform for in vitro mechanistic studies and drug discovery in cardiovascular disease.</p>","PeriodicalId":8905,"journal":{"name":"BMC Biotechnology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13450364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A dual pH/ROS-responsive hyaluronan-gated hollow mesoporous silica nanoplatform with CD44-associated cellular interaction improves curcumin retention under serum challenge and attenuates TNF-α-driven inflammatory outputs in rheumatoid arthritis synovial fibroblasts.","authors":"Ni Yan, Elaheh Pilehvar, Sepehr Mehdizadeh, Xiaoyan Li","doi":"10.1186/s12896-026-01169-3","DOIUrl":"10.1186/s12896-026-01169-3","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) synovitis is driven in part by activated fibroblast-like synoviocytes derived from rheumatoid arthritis tissue (RA-FLS), which amplify inflammatory and oxidative pathways that contribute to progressive joint damage. Curcumin (CUR) is mechanistically relevant to these pathogenic processes; however, its therapeutic utility is constrained by poor aqueous solubility, low bioavailability, and non-selective exposure. Here, we developed a hollow mesoporous silica nanoparticle (HMSN)-based nanodelivery platform that integrates an HA outer gate with a dual pH/reactive oxygen species (ROS)-responsive interfacial design. Unlike passive HA-coated carriers, this system was designed to combine serum-phase CUR retention with condition-dependent HA gate remodeling and CD44-associated cellular interaction. The final HA-gated formulation preserved the hollow HMSN architecture, achieved high CUR incorporation (encapsulation efficiency 73.55 ± 3.06%; drug loading 18.39 ± 0.77% w/w), and showed reduced baseline leakage under neutral conditions with increased release under combined acidic/oxidative stimulation. HA shedding assays and bonding-mode controls further supported stimulus-selective gate detachment rather than simple adsorption-related loss. Under protein challenge, the HA-gated system reduced premature CUR leakage relative to ungated HMSNs. In RA-FLS, it increased cell-associated CUR signal in a CD44-associated manner and, at matched CUR-equivalent dosing, produced the strongest suppression of metabolic viability, DNA synthesis, TNF-α-induced inflammatory and matrix-associated mediators, and intracellular ROS, while showing improved tolerability in healthy synoviocytes compared with free CUR. These findings support this HA-gated dual pH/ROS-responsive HMSN system as an in vitro proof-of-concept nanodelivery platform for improving CUR retention and RA-FLS-directed functional activity under inflammatory microenvironment-relevant conditions.</p>","PeriodicalId":8905,"journal":{"name":"BMC Biotechnology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13436291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial potential of different bee product-loaded carboxymethyl chitosan nanoparticles against multidrug-resistant clinical pathogens: a comparative in vitro study.","authors":"Asmaa K Helmy, Asmaa S El-Houssiny, Ahmed G Hegazi, Nagwa M Sidkey","doi":"10.1186/s12896-026-01159-5","DOIUrl":"10.1186/s12896-026-01159-5","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial resistance is one of the major public health threats facing humanity. Hence, the current investigation aimed to develop alternative therapeutic strategies by integrating apitherapy with biopolymer-based nanotechnology to combat multidrug-resistant (MDR) microbial pathogens.</p><p><strong>Methods: </strong>Out of 100 clinical microbial isolates, 29 highly MDR clinical pathogens from different infections, including Gram-negative and Gram-positive bacteria, as well as fluconazole-resistant Candida spp., were selected for the study. Three bee products (Turkish propolis extract (P), Egyptian honey (H), and Egyptian royal jelly (RJ)) were used, and their polyphenolic contents were determined via HPLC analysis. These bee products were encapsulated within carboxymethyl chitosan nanoparticles (CMC NPs). The resulting nano-formulations, namely Carboxymethyl chitosan-Propolis extract nanoparticles (CMC-P NPs), Carboxymethyl chitosan-Honey nanoparticles (CMC-H NPs), and Carboxymethyl chitosan-Royal Jelly nanoparticles (CMC-RJ NPs), were characterized in terms of particle size, surface charge, and chemical composition. Their antimicrobial activity and preliminary cytocompatibility were evaluated using standard microbiological assays and the MTT assay, respectively.</p><p><strong>Results: </strong>HPLC analysis confirmed the presence of diverse polyphenolic compounds in the bee products. The highest concentrations were detected in the ethanolic extract of propolis (EEP) (51.0-40993 µg/g), followed by honey (1.06-1591.16 µg/g) and royal jelly (0.53-2796.37 µg/g). Among the nano-formulations, CMC-P NPs emerged as the most potent formulation (size: 100.7 nm, zeta potential: -70 mV), showing significant bactericidal activity (P < 0.05) against all MDR isolates. Notably, CMC-P NPs exhibited inhibition zones (17.67-31.33 mm) and MIC values (0.019-1.25 mg/mL) that were superior to standard antibiotic controls. CMC-H NPs and CMC-RJ NPs exhibited variable antimicrobial effects, depending on the pathogen and the encapsulated bee product. Indeed, all three nano-formulations demonstrated strong antimicrobial action against highly resistant Klebsiella pneumoniae and Klebsiella ozaenae. Further, MTT assay results confirmed the preliminary biocompatibility of the nanostructures, showing no significant toxicity toward RPE1 cells.</p><p><strong>Conclusion: </strong>Encapsulation of bee products within CMC NPs significantly enhances their antimicrobial performance against a wide range of MDR clinical pathogens. The developed nano-formulations exhibited suitable physicochemical properties, potent antimicrobial activity, and promising preliminary biocompatibility, supporting their potential as safe and effective antimicrobial candidates for further preclinical investigation.</p>","PeriodicalId":8905,"journal":{"name":"BMC Biotechnology","volume":"26 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13220480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the molecular basis of arsenic resistance in Dietzia maris isolated from arsenic-contaminated soil.","authors":"Shahid Sher, Rosny Jean, Zaman Khan, Abdul Rehman","doi":"10.1186/s12896-026-01171-9","DOIUrl":"10.1186/s12896-026-01171-9","url":null,"abstract":"<p><strong>Background: </strong>The highly toxic nature and uncontrolled release of arsenic from anthropogenic activities into ecosystems create a huge health concern globally. Being a class 1 carcinogen, arsenic is affecting billions of people in both developed and developing countries.</p><p><strong>Results: </strong>Dietzia maris strain sha9 was isolated from industrially contaminated soil, screened phenotypically and genetically, and investigated for its potential in arsenic resistance and bioremediation. Minimum inhibitory concentration assay showed that it can tolerate < 36 mM arsenite and < 185 mM arsenate along with other multiple heavy metals and metalloids, including lead (5 mM), chromium (15 mM), cobalt (10 mM), selenium (7 mM), cadmium 6 mM), mercury (5 mM), and nickel (5 mM). The key genes for arsenic and other heavy metals were identified through whole-genome sequencing, and these genes include aioB, arsC, Acr3, arsR, csoR, copZ, and CzcD. Brownish precipitation upon reaction with AgNO₃ confirmed its oxidizing potential, and the arsenite oxidation potential assay showed 93% oxidizing capacity after 96 h. The experiment with wastewater and Milli-Q samples over time demonstrated the functional role of the strain in bioremediation, and the biomass of heat-inactivated cells also has a role in arsenic biosorption. Biochemical characterization highlighted higher intracellular glutathione levels and enhanced antioxidant enzyme activities such as catalase under arsenic stress, demonstrating the triggering of oxidative-stress defense mechanisms in the bacterium. The qPCR analysis further confirmed substantial induction of the aioB gene copy number and expression in the cells exposed to arsenite (almost threefold relative to control), and it is consistent with its pivotal role in the oxidation of arsenic.</p><p><strong>Conclusion: </strong>Collectively, these observations proved D. maris strain sha9 is a metabolically adaptable and genetically equipped arsenite-oxidizing bacterium with robust capability for arsenic bioremediation from contaminated sites.</p>","PeriodicalId":8905,"journal":{"name":"BMC Biotechnology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13450497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockdown of suppressor of glucose by autophagy (SOGA1) alleviates the progression of non-alcoholic steatohepatitis (NASH) by reducing hepatocyte senescence through regulating AMPK/mTOR-mediated mitochondrial homeostasis.","authors":"Lijing Yan, Huanhuan Sun, Tianyu Wang, Yuling Chen, Peijie Li","doi":"10.1186/s12896-026-01162-w","DOIUrl":"10.1186/s12896-026-01162-w","url":null,"abstract":"<p><p>Suppressor of glucose by autophagy (SOGA1), a lipid regulator, reprograms energy metabolism in the liver. However, whether SOGA1 is involved in the progression of nonalcoholic steatohepatitis (NASH) remains unclear. In this study, mice were fed a high-fat diet to construct a NASH mouse model with liver fibrosis, and the results showed that SOGA1 was upregulated in liver tissues of NASH mice. Hepatocytes (NCTC1469 cells) were treated with palmitic acid (PA), and the supernatant was isolated as conditioned medium (CM) to culture hepatic stellate cells (JS1 cells), simulating NASH in vitro. SOGA1 loss of function experiments showed that silencing SOGA1 decreased the levels of inflammatory factors (TNF-α and IL-6), fibrosis markers (α-SMA, COL1A1 and TGF-β1), senescence markers (p53, p21, γ-H2AX) and mitochondrial fusion markers (OPA1, MFN1, and MFN2), and elevated the levels of mitochondrial fission marker DRP1 and autophagy related protein LC3-II/I in PA-treated NCTC1469 cells. Furthermore, CM from SOGA1 silenced NCTC1469 cells reduced the protein levels of collagen I, III and α-SMA and decreased the viability in JS1 cells. Mechanistic studies showed that SOGA1 inhibits the activation of AMPK/mTOR pathway by recruiting RNF41, reducing mitophagy and mitochondrial homeostasis, thereby accelerating hepatocyte senescence. Senescent hepatocytes promote fibrosis by secreting IL-6 to activate hepatic stellate cells. Finally, lentiviral vectors of sh-SOGA1 were injected into NASH mice and found that SOGA1 knockout alleviated NASH progression in mice. In conclusion, SOGA1 knockdown may inhibit hepatocyte senescence and hepatic stellate cell activation by enhancing AMPK/mTOR-mediated mitochondrial homeostasis, thereby alleviating NASH progression.</p>","PeriodicalId":8905,"journal":{"name":"BMC Biotechnology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yeast surface display-based screening and preliminary characterization of nectin-4-targeting nanobodies for bladder cancer.","authors":"Jianhua Wen, Liangyi Wei, Jun Huang, Liujuan Zhou, Jiayin Yu, Hualin Cao, Haiqi Liang, Min Qin, Zelin Cui, Hao Chen, Yujian Li, Jiawen Zhao, Fubo Wang, Siming Liao, Jiwen Cheng","doi":"10.1186/s12896-026-01170-w","DOIUrl":"10.1186/s12896-026-01170-w","url":null,"abstract":"<p><strong>Background: </strong>Advanced bladder cancer (BCa) is associated with a poor prognosis, highlighting the urgent need for novel therapeutic strategies with improved efficacy and reduced toxicity. Nectin-4 (PVRL4, here after referred to as N4) is a clinically validated therapeutic target; however, existing antibody-based agents are limited by inadequate tumor penetration and off-target toxicities. Nanobodies (Nbs) possess favorable characteristics, including small molecular size, enhanced tissue penetration, and ease of sengineering. This study aimed to identify and preliminarily characterize N4-targeting Nb candidates for BCa using a yeast surface display-based screening strategy.</p><p><strong>Results: </strong>N4 was highly expressed in BCa and significantly associated with an unfavorable prognosis. The YSD platform supported efficient library expansion, surface display, and iterative enrichment of N4-binding clones. Among the identified Nbs, Nb-80 exhibited apparent binding activity, with an EC₅₀ of 0.150 μg/mL. BLI analysis demonstrated rapid association-dissociation kinetics.</p><p><strong>Conclusions: </strong>An N4-binding Nb candidate was identified and preliminarily characterized using a YSD-based screening strategy. These findings support the utility of the YSD platform for Nb discovery and provide a preliminary basis for further validation of N4-targeting Nb candidates in BCa.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":8905,"journal":{"name":"BMC Biotechnology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer effects of bisabolol oxide A-Loaded Micellar/Liposomal nanoparticles on DU-145 cells with deregulation of miR-34a and miR-181a: in silico and in vitro studies.","authors":"Shirin Fekri Kohan, Zohreh Arefi Khorrami, Fatemeh Bahrevar Fatideh, Shahin Nezamivand Chegini, Alireza Nouhi Kararoudi, Hossein Zahmatkesh, Behnam Rasti, Mohammad Nikpassand, Mahdi Shahriarinour, Najmeh Ranji, Yavuz Nuri Ertas","doi":"10.1186/s12896-026-01168-4","DOIUrl":"10.1186/s12896-026-01168-4","url":null,"abstract":"<p><p>Bisabolol oxide A, a key bioactive constituent of Matricaria chamomilla, is recognized for its potent anti-inflammatory, antioxidant, and anticancer properties. This study focused on synthesizing bisabolol oxide A-loaded micellar/liposomal nanoparticles (NPs) and rigorously evaluating their anti-proliferative and anti-invasive effects using integrated in vitro and in silico methodologies. Physicochemical characterization of the bisabolol oxide A-loaded NPs was performed using SEM, TEM, TGA-DTG, Zeta potential, DLS analysis, and FT-IR spectroscopy. Furthermore, drug-like properties for bisabolol oxide A, bisabolol oxide B, and 5,8,11-heptadecatriynoic acid methyl ester were predicted using Swiss ADME software. Molecular dynamics simulations were subsequently conducted for these compounds against critical cellular migration proteins: β-catenin and the Epidermal Growth Factor Receptor (EGFR). The anticancer efficacy of the bisabolol oxide A-loaded nanoparticles was assessed through MTT assays, Annexin V/PI staining, wound healing assays, and qRT-PCR. Characterizations confirmed that the nanoparticles possessed optimal characteristics, exhibiting sizes between 35 to 67 nm, high mono-dispersity and thermal stability up to 380°C. In vitro results demonstrated that bisabolol oxide A-loaded micellar/liposomal nanoparticles significantly inhibited DU-145 cell proliferation, yielding IC₅₀ value of 55.44 µg/mL, 46.21 µg/mL, and 43.59 µg/mL after 24, 48, and 72 hours of treatment. Flow-cytometry analysis further confirmed 50.04% reduced migratory capacity and induction of apoptosis. Mechanistically, qRT-PCR analysis revealed a significant 2.31 ± 0.16-fold upregulation of the tumor-suppressive miR-34a and a 1.72 ± 0.03-fold downregulation of the oncomiR miR-181a in treated cells. These miRNA alterations correlated with the downregulation of migration-associated genes (CTNNB, SMAD3, and EGFR) and the upregulation of apoptosis-related genes (P53 and CASP9), findings substantiated by Western blot analysis. In silico analyses indicated favorable ADMET properties for bisabolol oxide A, bisabolol oxide B, and 5,8,11-heptadecatriyneoic acid methyl ester. Molecular docking simulations revealed strong binding affinities of these compounds for β-catenin and EGFR, which are key proteins in cellular migration pathways. Our findings strongly suggest that bisabolol oxide A functions as an anti-migration and pro-apoptotic agent by effectively modulating the expression of specific miRNAs and their transcriptional targets, complemented by potent inhibitory interactions with critical protein targets.</p>","PeriodicalId":8905,"journal":{"name":"BMC Biotechnology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}