Biochemistry and Biophysics Reports最新文献

{"title":"Expression and purification of a broad-spectrum human protease inhibitor in Pichia pastoris","authors":"Varsha Bhakta ,&nbsp;Negin Chaeichi Tehrani ,&nbsp;Antje Ask ,&nbsp;William P. Sheffield","doi":"10.1016/j.bbrep.2025.102092","DOIUrl":"10.1016/j.bbrep.2025.102092","url":null,"abstract":"<div><div>Alpha-1 antitrypsin (AAT) is the most abundant member of the serpin superfamily of protease inhibitors found in human plasma. Expression of a broad-spectrum AAT variant (AAT M358R) and an AAT variant (AAT-RC-2) that specifically inhibits coagulation Factor XIa (FXIa) in the methylotrophic yeast <em>Pichia pastoris</em> were compared. When protein secretion was directed by the 85 amino acid <em>Saccharomyces cerevisiae</em> alpha mating factor (AMF) prepro signal sequence 1 (ss1), AAT-RC-2 was purified as a 45 kDa homogeneous polypeptide preparation, but AAT M358R was heterogeneous. Replacement of the ss1 prepro sequence with any of 5 presequences lacking pro sequences eliminated the heterogeneity. The highest yield was obtained with ss3-AAT M358R, where ss3 was the 19 amino acid <em>Saccharomyces cerevisiae</em> AMF presequence. Enzymatic deglycosylation of ss1-AAT M358R converted its high molecular weight heterogeneity into a simple combination of 55 kDa and 45 kDa polypeptides consistent with failure to remove the AMF presequence and inhibition of the Kex2 propeptide convertase by AAT M358R. Purified ss3-AAT M358R inhibited FXIa significantly more rapidly than <em>E. coli</em>-derived AAT M358R with indistinguishable reaction stoichiometry; purified ss1-AAT-RC-2 did not differ from its <em>E. coli</em>-derived counterpart in either kinetic parameter. Both AAT variants formed denaturation-resistant complexes with FXIa. Substitution of the AMF prepro sequence with its constituent presequence eliminated the protein expression problem caused by inhibition of the <em>Pichia pastoris</em> propeptide processing machinery by AAT M358R and will make feasible comparison of AAT M358R and AAT-RC-2 in animal models of thrombosis and bleeding.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102092"},"PeriodicalIF":2.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNAs IFNG-AS1 and TH2LCRR as potential biomarkers of Th1/Th2 imbalance in diabetic nephropathy: From bioinformatics to experimental validation","authors":"Seyed Amir Hossein Hosseini ,&nbsp;Parisa Ajorlou ,&nbsp;Maryam Salehian ,&nbsp;Aghdas Dehghani","doi":"10.1016/j.bbrep.2025.102093","DOIUrl":"10.1016/j.bbrep.2025.102093","url":null,"abstract":"<div><h3>Background</h3><div>The inflammatory response is a pivotal mechanism underlying the progression of type 2 diabetes mellitus (T2DM) into diabetic nephropathy (DN). Upstream lncRNAs regulate inflammatory molecules, and their dysregulation can disrupt immune homeostasis. Th1/Th2 imbalance is one of the most significant causes of DN progression. This research aims to uncover novel biomarkers and elucidate the underlying molecular mechanisms involved in DN.</div></div><div><h3>Methods</h3><div>The GSE135390 dataset was analyzed to identify differentially expressed genes (DEGs) associated with Th1 cell differentiation. Based on literature review and NcPath databases, IFNG-AS1(Th1) and TH2LCRR (Th2) were selected as the top lncRNAs. To validate our bioinformatics findings, real-time PCR was conducted on 90 participants categorized into four groups: 30 with T2DM, 30 with DN (15 with microalbuminuria and 15 with ESRD), and 30 healthy controls.</div></div><div><h3>Results</h3><div>The analysis of real-time PCR results revealed a notable upregulation in IFNG-AS1 expression in ESRD patients compared to individuals with T2DM and healthy controls. Moreover, a significant increase in IFNG-AS1 expression was observed in patients with microalbuminuria relative to healthy subjects. Conversely, TH2LCRR expression was notably reduced in patients with ESRD, microalbuminuria, and T2DM compared to healthy individuals. Expression of IFNG-AS1 and TH2LCRR showed strong correlation with biochemical markers, including HbA1c, ESR, BUN, GFR, and albumin.</div></div><div><h3>Conclusion</h3><div>This study demonstrates the potential role of IFNG-AS1 and TH2LCRR as key regulators in the immunopathogenesis of DN. Their dysregulated expression may contribute to Th1/Th2 imbalance, providing a deeper understanding of immune-mediated mechanisms involved in DN progression.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102093"},"PeriodicalIF":2.3,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and characterization of gene networks and key genes related to the high-yield production of milk in high-yield cows using meta-analysis of microarray data","authors":"Mahdi Rahmatzadeh ,&nbsp;Reza Shokri-Gharelo ,&nbsp;Morteza Derakhti-Dizaji ,&nbsp;Asghar Bazzaz ,&nbsp;Bizhan Mahmoudi","doi":"10.1016/j.bbrep.2025.102090","DOIUrl":"10.1016/j.bbrep.2025.102090","url":null,"abstract":"<div><div>Milk yield is most important economic trait in dairy cows and understanding molecular basis and components involved in high-yield production is one of crucial steps to develop and select new breeds. In this study, we used combination of two statistical methods based on the <em>p-value</em> and effect sized to meta-analysis three datasets followed with construction of weighted gene co-expression network based on the expression matrix of differentially expressed genes identified in meta-analysis to detect major gene modules and hub genes. Based on the FDR cut-off&lt;0.05 and Log₂ fold change&gt;2 and &lt; 0.5, we identified 1028 differentially expressed genes that were shared between the Fisher and REM method and were consistent across datasets. Molecular function analysis showed that upregulated differentially expressed genes mostly enriched to ion binding, small molecule binding, and identical protein binding while downregulated genes were enriched to catalytic activity (Bonferroni test; threshold of 0.05). Weighted gene co-expression network analysis identified three major modules associated with fatty acid metabolism, PPAR signaling pathway, insulin resistance, terpenoid backbone biosynthesis, and steroid biosynthesis. A total of 12 hub genes (one downregulated and 11 upregulated) identified from protein-protein interaction network of modules. This study could identify new differentially expressed genes related to lactation processes in high-yield-cows. Moreover, we could reveal some gene modules and hub genes in each module which are biologically more meaningful.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102090"},"PeriodicalIF":2.3,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro evaluation of antimicrobial, antitumor, and anti-SARS-cov-2 properties of cellulase enzyme produced by Aspergillus niger","authors":"Mahmoud S. Abdelnabi ,&nbsp;Nouran H. Assar ,&nbsp;Amal S. Shahat ,&nbsp;Omnia Kutkat ,&nbsp;Rehab Bahy","doi":"10.1016/j.bbrep.2025.102080","DOIUrl":"10.1016/j.bbrep.2025.102080","url":null,"abstract":"<div><h3>Background</h3><div>Microbial enzymes, particularly cellulases, are widely used in industrial processes; however, their therapeutic potential remains underexplored. This study investigates the antibacterial, antitumor, and antiviral properties of a cellulase enzyme produced by <em>Aspergillus niger</em> using coir waste as a substrate.</div></div><div><h3>Methods</h3><div>Cellulase production was carried out via solid-state fermentation. Antimicrobial activity was evaluated against <em>Staphylococcus aureus</em> (ATCC 29737), <em>Pseudomonas aeruginosa</em> (ATCC 25619), and MRSA. The synergistic antibiofilm effect of cellulase with azithromycin was assessed. Cytotoxicity against MDA-MB-231 breast cancer cells was analyzed using MTT assay, DPPH radical scavenging activity, caspase-3 activation, and cytokine profiling (TNF-α, IL-6, IL-10). Antiviral activity against SARS-CoV-2 was also examined.</div></div><div><h3>Results</h3><div>The produced cellulase exhibited an activity of 3.7 U/mL. No direct bactericidal effect was observed, but a significant synergistic reduction in biofilm biomass was noted with azithromycin. The enzyme reduced cancer cell viability, increased antioxidant (DPPH) activity, elevated caspase-3 levels, and modulated cytokine expression by decreasing TNF-α and IL-6 while increasing IL-10. Notably, the enzyme formulation demonstrated strong antiviral activity against SARS-CoV-2.</div></div><div><h3>Conclusion</h3><div>Cellulase derived from <em>A. niger</em> presents significant biological potential, including antibiofilm, anticancer, immunomodulatory, and antiviral properties. These findings suggest promising applications of microbial cellulase in therapeutic development.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102080"},"PeriodicalIF":2.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A robust comprehensive immunoinformatics approach for designing a potential multi-epitope based vaccine against a reiterated monkeypox virus","authors":"Khalid Hasan Raj,&nbsp;Emam Hossain,&nbsp;Hasnat Zahin,&nbsp;Abdullah Al Noman,&nbsp;Abdullah Al Saba,&nbsp;Mohammad Sayem,&nbsp;Tahirah Yasmin,&nbsp;A.H.M. Nurun Nabi","doi":"10.1016/j.bbrep.2025.102075","DOIUrl":"10.1016/j.bbrep.2025.102075","url":null,"abstract":"<div><div>Mpox, a viral disease, caused by the monkeypox virus (MPXV) has been a public health emergency of international concern since 2024. The absence of any mpox-specific treatment or vaccine, along with the emergence of new variants like Clade Ib, underscores the urgent need for targeted vaccine development. To address the challenge, this study employed reverse vaccinology and immunoinformatics approaches to design a multi-epitope vaccine against MPXV. The vaccine construct includes four Linear B lymphocyte (LBL), nine Cytotoxic T lymphocyte (CTL), and seven Helper T lymphocyte (HTL) epitopes. LBL epitopes were selected from six membrane glycoproteins of the virus and the T-cell epitopes were selected from the experimentally validated conserved epitopes of the similar orthopoxviruses. These epitopes were combined with appropriate linkers and adjuvants to enhance structural flexibility, immunogenicity, and potency. The engineered vaccine underwent rigorous evaluation, considering physicochemical properties, structural integrity, population coverage, and immune system response through simulation. The 3D structure of the vaccine was predicted, optimized, and docking analysis revealed robust interactions with the human Toll-like receptor 2 and 4 (TLR-2 and TLR-4), supported by highly negative HADDOCK scores and low RMSD values. The stability of the vaccine construct and its stable interaction with TLR-2 and TLR-4 were confirmed by molecular dynamics (MD) simulation. Additionally, the immune simulation results showed that the vaccination significantly increased IgM levels during the primary response, while IgG subtypes as well as combined IgM and IgG levels nearly doubled in the secondary and tertiary responses. <em>In silico</em> expression in <em>Escherichia coli</em> (<em>E. coli</em>) further confirmed its potential for production. Overall, this study presents a highly immunogenic and promising vaccine candidate against MPXV that demands experimental validation for clinical application.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102075"},"PeriodicalIF":2.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network-based analysis of candidate oncogenes and pathways in hepatocellular carcinoma","authors":"Nasim Rahimi-Farsi ,&nbsp;Taha Shahbazi ,&nbsp;Abozar Ghorbani ,&nbsp;Negar Mottaghi-Dastjerdi ,&nbsp;Fateme Yazdani ,&nbsp;Parvin Mohseni ,&nbsp;Pietro Hiram Guzzi ,&nbsp;Gita Esmail nia ,&nbsp;Behzad Shahbazi ,&nbsp;Khadijeh Ahmadi","doi":"10.1016/j.bbrep.2025.102086","DOIUrl":"10.1016/j.bbrep.2025.102086","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a major worldwide health burden due to poor outcomes. Identifying dysregulated molecular circuits in HCC is critical for developing precise treatments. A systems-level approach using multi-omics data is required to reveal the intricate non-linear interactions underlying liver carcinogenesis. Both tumor and control tissues contained differentially expressed genes (DEGs). Hub genes with the strongest connection were identified as potential drivers. Protein-protein interaction (PPI) mapping verified hub connectivity. Perturbed functions were evaluated using Gene Ontology and KEGG pathway enrichment analysis. Cytoscape clustering separated the interactome into modules. Motif discovery indicated a shift in <em>cis</em>-regulatory logic. Expression analysis, survival analysis, and drug screening were performed on the hub genes.</div><div>Network hub gene analysis identified 11 hub genes, including DLGAP5, KIF23, KIF11, CCNB1, CDK1, BRCA1, CCNA2, SHCBP1, KIAA0101, FAM83D, and SPC25. Gene set enrichment analysis (GSEA) revealed dysregulation in cell cycle progression, DNA damage response, and metabolic pathways, and an association of these genes with reduced overall survival in HCC patients. Also, drug screening identified potential therapeutic agents targeting these hub genes.The findings increase mechanistic understanding with potential clinical applications. Future validation studies that include multi-omic data may strengthen current hypotheses and enable targeted therapy design against crucial in HCC.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102086"},"PeriodicalIF":2.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive phytochemical profiling of bioactive compounds from Barleria prattensis for their antioxidant and cytotoxic capacity and its characterization using GC-MS","authors":"Saif Saleh Mohsen Ali ,&nbsp;Pushpa Robin","doi":"10.1016/j.bbrep.2025.102083","DOIUrl":"10.1016/j.bbrep.2025.102083","url":null,"abstract":"<div><div><em>Barleria prattensis</em> Santapau has been traditionally used for its medicinal properties, particularly for its antimicrobial and antioxidant benefits. This study evaluates its phytochemical composition, total phenolic content (TPC), total flavonoid content (TFC), antioxidant activity, and anticancer potential. Phytochemical screening was conducted using standard qualitative assays, while TPC and TFC were quantified using the Folin–Ciocalteu and aluminum chloride methods, respectively. The TPC values for methanol (MeOH), chloroform (CHCl₃), and petroleum ether (PE) extracts were 72.9, 37.3, and 16.6 mg GAE/g, whereas TFC values were 43.4, 28.1, and 18.3 mg QE/g, respectively. Antioxidant activity was assessed using the DPPH radical scavenging assay, with IC₅₀ values of 7.46, 16.13, 66.95, and 112.97 μg/mL for ascorbic acid (AA), MeOH, CHCl₃, and PE, respectively. Cytotoxicity against the MCF-7 breast cancer cell line was evaluated using the MTT assay, with IC₅₀ values of 293.6 μg/mL for MeOH, 260.0 μg/mL for CHCl₃, and 60.1 μg/mL for PE. Morphological analysis confirmed apoptotic changes in treated MCF-7 cells compared to untreated controls. GC-MS analysis identified key bioactive compounds, including phytol, squalene, neophytadiene and β-sitosterol, which are known for their antioxidant and anticancer properties. The methanolic extract exhibited the highest antioxidant activity, comparable to ascorbic acid, while the PE extract showed the strongest cytotoxic effect. This study provides novel insights into the dual therapeutic potential of <em>B. prattensis</em>, underscoring its role as a rich source of antioxidant and anticancer phytochemicals. The superior cytotoxicity of the PE extract and the methanolic extract's radical scavenging efficacy highlight its viability for developing plant-based therapies for oxidative stress-related disorders and breast cancer. Further isolation and characterization of bioactive compounds, including squalene, phytol, and neophytadiene, which are the most abundant in this plant, could support drug discovery and the development of new therapeutic agents.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102083"},"PeriodicalIF":2.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxyfunctionalisation of anisole and its selected reaction products by unspecific peroxygenases","authors":"Essi Rytkönen ,&nbsp;Janne Jänis ,&nbsp;Anu Koivula ,&nbsp;Juha Rouvinen","doi":"10.1016/j.bbrep.2025.102088","DOIUrl":"10.1016/j.bbrep.2025.102088","url":null,"abstract":"<div><div>Unspecific peroxygenases (UPOs) are fungal enzymes capable of oxidizing hundreds of different organic compounds using hydrogen peroxide as the sole co-substrate. Aromatic ethers are among the less-studied substrates for UPOs, even though they offer a potential route to valuable phenolic compounds, such as those derived from the depolymerized lignin as a feedstock. Consequently, the oxyfunctionalisation potential of a panel of 30 UPO enzymes, along with <em>Agrocybe aegerita</em> UPO, was investigated using a simple aromatic ether, anisole. Anisole oxyfunctionalisation by the studied UPOs involved up to four consecutive reactions, resulting in the detection of 14 different products. Aromatic hydroxylation was the primary reaction pathway, leading to methoxyphenols or methoxybenzenediols. <em>O</em>-Demethylation also occurred, as phenol and benzenediols were identified among the products. As expected, different UPOs produced varying products and yields; however, guaiacol and 4-methoxyphenol were detected with every enzyme. The effect of ascorbic acid as a radical scavenger was also assessed, given that radical reactions leading to oligomerisation can occur with phenolic products. Generally, the presence of ascorbic acid broadened the product range, potentially due to the detection of trace products and a reduction in quinone formation. Owing to the broad product scope with anisole, biotransformations were also carried out with the identified phenolic intermediates to evaluate further oxidation routes. Based on these findings, a reaction pathway for anisole was proposed, offering insights into potential applications of UPOs in the tailored oxyfunctionalisation of phenolic substrates.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102088"},"PeriodicalIF":2.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards precision epitopes based vaccine against Enterococcus faecalis by integrating vaccinomics, reverse vaccinology and biophysics approaches","authors":"Asad Ullah ,&nbsp;Sadiq Azam ,&nbsp;Sajjad Ahmad ,&nbsp;Ibrar Khan ,&nbsp;Dalia M. Alammari ,&nbsp;Sumra Wajid Abassi ,&nbsp;Dong-Qing Wei ,&nbsp;Fahad M. Alshabrmi ,&nbsp;Mohammad Abdullah Aljasir ,&nbsp;Eid A. Alatawi","doi":"10.1016/j.bbrep.2025.102082","DOIUrl":"10.1016/j.bbrep.2025.102082","url":null,"abstract":"<div><div><em>Enterococcus faecalis</em> is a Gram-positive bacterium and recognized as an etiological agent of different nosocomial infections. <em>E. faecalis</em> has developed resistance to several antibiotics. No licensed vaccine is available to prevent <em>E. faecalis</em> infections. A multi-epitopes-based vaccine construct may provide effective vaccine design foundation. In this study, an integrated bioinformatic approach was applied to design of a multi-epitopes-based vaccine construct against <em>E. faecalis</em>. In subtractive proteomics analysis, 10 proteins were prioritized as potential vaccine candidates based on several literature reported vaccine candidacy parameters. In immunoinformatics analysis, only two proteins (glucosaminidase domain-containing protein and serine protease) were found as promising vaccine targets. Both proteins were then subjected to epitopes mapping for screening of broad-spectrum antigenic epitopes. The predicted epitopes were further refined based on immunoinformatics filters and only six epitopes; DTSDHQKNNV, GMKKRKARY, SVFDESMALR, NLNQRIEKR, NVDKKIEEK, and TTTPSTDNSA were found as non-allergic, antigenic, water-soluble, non-toxic and DRB∗0101 good binders. The selected epitopes were fused via GPGPG linkers and additionally linked to an adjuvant molecule through EAAAK linkers to increase the immunogenicity and antigenicity of the vaccine construct. The net interactions energy of the vaccine and receptors was evaluated through molecular docking analysis, which predicted −833.0 kcal/mol and −1001.6 kcal/mol of binding energy for MHC-I and MHC-II, respectively. The values predict effective vaccine construct binding with host immune cell receptors and triggering of innate and adaptive immune responses. The dynamic behavior of the docked complexes was examined using molecular dynamics (MD) simulation technique on a time scale of 500 ns. The MD revealed minimal intermolecular conformational deviations and exposed presentation of the vaccine epitopes for immune cells recognition and processing. For MHC-I-Vaccine complex, the mean RMSD was found as 2.78 Å while MHC–II–Vaccine complex showed a mean RMSD value of 13.17 Å. The C-immune simulation predicted the formation of high titer humoral and cellular immunological responses against the vaccine antigen. The predicted IgG and IgM titer found against the antigen was 600000–650000 counts per milliliter. The interferon-gamma (IFN-γ) was predicted to be stimulated at 430000 ng per milliliter. Simulation trajectories based MMGB/PBSA binding energy was estimated as &lt; −250 kcal/mol for vaccine-MHC complexes, illustrating formation of robust interactions between the vaccine and MHC receptors. The study outcomes predicted the viability of the proposed epitope-based vaccine construct as a promising therapeutic approach for <em>E. faecalis</em> infections prevention, however, experimental confirmation is required.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102082"},"PeriodicalIF":2.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing the expression profile of Dexras1 in human trabecular meshwork cells","authors":"ChihWei Chen ,&nbsp;Jiapeng Han ,&nbsp;Luis Sanchez ,&nbsp;Judy L. Chen ,&nbsp;Jie J. Zheng","doi":"10.1016/j.bbrep.2025.102077","DOIUrl":"10.1016/j.bbrep.2025.102077","url":null,"abstract":"<div><div>Corticosteroids are a mainstay therapy for the treatment of ocular and systemic inflammatory conditions but are associated with a significant risk of intraocular pressure elevation, or ocular hypertension. If intraocular pressure is inadequately controlled, steroid-induced glaucoma may develop, which can result in permanent vision loss and irreversible blindness. Pathological changes akin to fibrosis in the trabecular meshwork, the tissue responsible for intraocular pressure regulation, have been well described and contribute to the development of steroid-induced ocular hypertension and glaucoma. However, the molecular mechanisms driving these fibrosis-like changes in the trabecular meshwork following steroid treatment remain poorly understood. <em>RASD1</em> is a gene coding for Dexras1, a small G protein of the Ras family discovered based on its marked induction by the synthetic glucocorticoid dexamethasone. Accumulating evidence points to the role of glucocorticoids in alterations of trabecular meshwork cell morphology, growth, and cell-extracellular matrix interactions. Therefore, we sought to confirm and further characterize how glucocorticoid-induced Dexras1 expression may contribute to glaucoma pathology <em>in vitro</em>. In this study, we found that dexamethasone significantly upregulated the expression of Dexras1 in trabecular meshwork cells within 30 min to 1 h post treatment. In addition, we discovered two phenotypes of Dexras1 induction independent of glucocorticoid responsiveness: younger and older donors show significant upregulation of Dexras1, whereas middle-aged donors experience little to no changes in Dexras1 expression after dexamethasone treatment. This age-dependent Dexras1 response may provide a novel explanation for the greater prevalence of steroid-induced glaucoma observed in older and younger populations as opposed to middle-aged populations.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102077"},"PeriodicalIF":2.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}