Selin Ursavas , Yurdun Kuyucu , Ebru Dundar Yenilmez , Abdullah Tuli , Muhammetnur Tekayev , Ufuk O. Mete
{"title":"The evaluation of the effects of metformin on the rat testes at a light and electron microscopic level","authors":"Selin Ursavas , Yurdun Kuyucu , Ebru Dundar Yenilmez , Abdullah Tuli , Muhammetnur Tekayev , Ufuk O. Mete","doi":"10.1016/j.bbrc.2025.151507","DOIUrl":"10.1016/j.bbrc.2025.151507","url":null,"abstract":"<div><div>The present study aimed to assess the histological and ultrastructural changes in the testes induced by metformin. Eighteen adult male Wistar rats were divided into three groups: a control group, a low-dose metformin group, and a high-dose metformin group. Following thirty days of metformin administration, blood samples, and testes tissues were collected and subjected to biochemical, histological, and ultrastructural analyses. In the groups treated with metformin, degenerative changes were observed, including irregular seminiferous tubules, disruption of epithelial integrity, a decrease in spermatogenic cells, and dilated intercellular spaces. These changes were evident in both the light and electron microscopic evaluations, and the severity varied depending on the metformin dosage. The findings showed that the diameter of the seminiferous epithelium and epithelium height decreased significantly in the high-dose group. Also, Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), and testosterone levels altered significantly, with increased levels of all hormones observed in the high-dose metformin-administered group than in the control group. For the markers of oxidative stress and antioxidant status respectively there were no significant differences observed in the levels of Malondialdehyde (MDA) between the groups, however, Superoxide dismutase (SOD) activity significantly decreased in the high-dose metformin-administered group compared to the control group.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"753 ","pages":"Article 151507"},"PeriodicalIF":2.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shanshan Tan , Guoquan Fu , Yixia Xie , Xueying Xie , Junyan Yan , Lifang Jin
{"title":"HDAC6 deficiency aggravates ductular reactions through aggresome-mediated hepatocyte apoptosis","authors":"Shanshan Tan , Guoquan Fu , Yixia Xie , Xueying Xie , Junyan Yan , Lifang Jin","doi":"10.1016/j.bbrc.2025.151511","DOIUrl":"10.1016/j.bbrc.2025.151511","url":null,"abstract":"<div><div>Ductular reactions (DRs) contribute significantly to the occurrence and development of liver disease. While histone deacetylase 6 (HDAC6) is known to regulate injury repair in multiple tissues, its exact role in DRs remains unclear. This study examined the role and underlying mechanism of HDAC6 in DRs using an HDAC6 knockout (HDAC6<sup>−/y</sup>) male mouse model. Wild type and HDAC6-deficient male mice were administered 3,5 diethoxicarbonyl-1,4 dihydrocollidine (DDC) to induce DRs. The impact of HDAC6 inhibition on aggresome formation was assessed <em>in vitro</em> using AML-12 hepatocytes exposed to H<sub>2</sub>O<sub>2</sub> and treated with tubastatin A (TSA), a selective HDAC6 inhibitor. Fluorescence immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to quantify protein and gene expression levels, respectively. Immunohistochemical and qRT-PCR analyses revealed that HDAC6 deficiency exacerbated DRs and fibrosis, accompanied by increased expression of transforming growth factor β (TGF-β) and activation of the Notch signaling pathway. Additionally, genetic knockout or pharmacological inhibition of HDAC6 promoted hepatocyte apoptosis <em>in vivo</em> and <em>in vitro</em>, as evidenced by elevated <em>caspase3</em>, <em>caspase9</em>, and <em>p53</em> expression. Furthermore, TSA treatment induced the formation of aggresomes in H<sub>2</sub>O<sub>2</sub>-exposed AML-12 hepatocytes, which were encased by vimentin filaments. These findings demonstrate that HDAC6 deficiency promotes DRs and liver fibrosis through the formation of intracellular aggregates, ultimately leading to hepatocyte apoptosis.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"753 ","pages":"Article 151511"},"PeriodicalIF":2.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Radioprotection and enhanced efficacy by curcumin-loaded chitosan nanoparticles in mitigating radiation-induced liver injury","authors":"Rasool Azmoonfar , Masoud Moslehi , Daryoush Shahbazi-Gahrouei , Elham Shiri , Mehdi Azizi","doi":"10.1016/j.bbrc.2025.151512","DOIUrl":"10.1016/j.bbrc.2025.151512","url":null,"abstract":"<div><h3>Introduction</h3><div>This study aimed to evaluate the protective effect of curcumin-loaded chitosan nanoparticles (Cur-CsNPs) against radiation-induced liver damage in rats. Curcumin's antioxidant and anti-inflammatory properties, combined with chitosan's drug delivery potential, were leveraged to mitigate the harmful effects of ionizing radiation (IR) on the liver.</div></div><div><h3>Methods</h3><div>Cur-CsNPs were characterized using TEM, XRD, DLS, and FTIR. Spectrophotometry assessed drug loading and curcumin release. Cytotoxicity was evaluated using MTT assay on HepG2 cells. The experimental design involved eight groups: a control group, three groups receiving different doses of Cur-CsNPs (25, 50, 100 mg/kg), three groups receiving the same doses plus irradiation (6Gy), and one group receiving irradiation only. H&E and MTC staining were used for histopathological evaluation. The activity of liver enzymes ALT, AST, ALP, and GGT was measured.</div></div><div><h3>Results</h3><div>In this study, three types of Cur-CsNPs were synthesized using varying ratios of chitosan to TPP ratios, resulting in average sizes of 660 nm, 230 nm, and 120 nm. Cur-CsNPs which exhibited the highest encapsulation efficiency, was selected for further evaluation. TEM confirmed its spherical shape with an average size of 37 nm. Drug release studies demonstrated an 85 % release at pH 5.4 within 70 h. MTT assays indicated low cytotoxicity, with high cell viability maintained across all concentrations and time points. Liver enzyme analysis in rats revealed that Cur-CsNPs, particularly when combined with radiation, mitigated radiation-induced liver damage. Histological examination showed that treatment with Cur-CsNPs reduced liver damage, inflammation, necrosis, and fibrosis in irradiated groups compared to the radiation-only group, which exhibited severe liver damage.</div></div><div><h3>Conclusion</h3><div>The findings of this study show that Cur-CsNPs possess significant potential as a therapeutic agent for protecting against radiation-induced liver injury. The favorable drug release profile, low cytotoxicity, and protective effects observed in enzyme levels and histological assessments highlight the efficacy of Cur-CsNPs. The findings imply that Cur-CsNPs could be an effective strategy for enhancing liver protection in radiation exposure scenarios, warranting further investigation into their mechanisms of action and potential clinical applications<strong>.</strong></div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"753 ","pages":"Article 151512"},"PeriodicalIF":2.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitochondrial targeted therapies in MAFLD","authors":"Sien Lai, Dongsheng Tang, Juan Feng","doi":"10.1016/j.bbrc.2025.151498","DOIUrl":"10.1016/j.bbrc.2025.151498","url":null,"abstract":"<div><div>Metabolic dysfunction-associated fatty liver disease (MAFLD) is a clinical-pathological syndrome primarily characterized by excessive accumulation of fat in hepatocytes, independent of alcohol consumption and other well-established hepatotoxic agents. Mitochondrial dysfunction is widely acknowledged as a pivotal factor in the pathogenesis of various diseases, including cardiovascular diseases, cancer, neurodegenerative disorders, and metabolic diseases such as obesity and obesity-associated MAFLD. Mitochondria are dynamic cellular organelles capable of modifying their functions and structures to accommodate the metabolic demands of cells. In the context of MAFLD, the excess production of reactive oxygen species induces oxidative stress, leading to mitochondrial dysfunction, which subsequently promotes metabolic disorders, fat accumulation, and the infiltration of inflammatory cells in liver and adipose tissue. This review aims to systematically analyze the role of mitochondria-targeted therapies in MAFLD, evaluate current therapeutic strategies, and explore future directions in this rapidly evolving field. We specifically focus on the molecular mechanisms underlying mitochondrial dysfunction, emerging therapeutic approaches, and their clinical implications. This is of significant importance for the development of new therapeutic approaches for these metabolic disorders.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"753 ","pages":"Article 151498"},"PeriodicalIF":2.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mariana Juliani do Amaral , Letícia Soares de Oliveira, Yraima Cordeiro
{"title":"Zinc ions trigger the prion protein liquid-liquid phase separation","authors":"Mariana Juliani do Amaral , Letícia Soares de Oliveira, Yraima Cordeiro","doi":"10.1016/j.bbrc.2025.151489","DOIUrl":"10.1016/j.bbrc.2025.151489","url":null,"abstract":"<div><div>Prion diseases are characterized by the misfolding and conversion of the monomeric prion protein (PrP) to a multimeric aggregated pathogenic form, known as PrP<sup>Sc</sup>. We and others have recently shown that biomolecular condensates formed via liquid-liquid phase separation of PrP can undergo maturation to solid-like species that resemble pathological aggregates, and this process is modulated by DNA, RNA, and oxidative conditions. Conversely, the most well-studied ligand of PrP, copper ions, induce liquid-like condensates of PrP that accumulate Cu<sup>2+</sup> <em>in vitro</em>, and live PrP<sup>C</sup>-expressing cells show condensation at the cell surface as triggered by physiologically relevant conditions of Cu<sup>2+</sup> and protein concentrations. Since PrP can also bind to Zn<sup>2+</sup> through its intrinsically disordered N-terminal domain, though with different affinities and binding modes than Cu<sup>2+</sup>, we hypothesized that Zn<sup>2+</sup> could modulate PrP phase separation differently from copper ions. Using an appropriate buffer with negligible metal ion binding, as well as relevant pH, ionic strength, molecular crowding, and Zn<sup>2+</sup> concentrations, we show that recombinant PrP undergoes phase separation with Zn<sup>2+</sup>. <span>Furthermore</span>, we show that metal ion-induced condensation of PrP is dependent on the N-terminal domain (residues 23–90). <em>In vitro</em> Fluorescence Recovery After Photobleaching (FRAP) experiments and thioflavin T aggregation kinetics support key differences in the molecular properties of PrP:Zn<sup>2+</sup> <em>versus</em> PrP:Cu<sup>2+</sup> phase separated states. FRAP analysis indicated that both Cu<sup>2+</sup> and Zn<sup>2+</sup> promote liquid-like PrP condensates; however, PrP:Zn<sup>2+</sup>condensates exhibit a faster recovery. Cu<sup>2+</sup> pronouncedly inhibits seed-induced PrP misfolding, whereas Zn<sup>2+</sup> provides a milder delay in PrP aggregation. Our findings provide insights on Zn<sup>2+</sup>-induced phase separation of PrP, supporting a variety of previously proposed functions of PrP in metal sequestering and uptake, processes that could be effectively regulated through biomolecular condensation.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"753 ","pages":"Article 151489"},"PeriodicalIF":2.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haidong He , Yifan Zhu , Xiaoguo Ji , Suying Pu , Hui Zheng
{"title":"The miR-22–5p/Clec4e axis has diagnostic potential in fructose-induced nonalcoholic fatty liver disease","authors":"Haidong He , Yifan Zhu , Xiaoguo Ji , Suying Pu , Hui Zheng","doi":"10.1016/j.bbrc.2025.151496","DOIUrl":"10.1016/j.bbrc.2025.151496","url":null,"abstract":"<div><div>Nonalcoholic fatty liver disease (NAFLD) is significantly influenced by microRNAs in its development and progression. This study aimed to identify microRNA profiles and RNA regulatory networks for NAFLD intervention. Mice were fed a high-fructose diet (HFrD) to induce NAFLD. Small RNA-seq and mRNA-seq were used to analyze liver microRNA and mRNA profiles of HFrD-fed versus normal chow-fed (Chow) mice. The differentially expressed genes (DEGs) and miRNAs (DE-miRNAs) were identified, followed by enrichment analysis. A protein‒protein interaction network of overlapping DEGs and DE-miRNA targets was constructed, along with a competing endogenous RNA (ceRNA) network. Mendelian randomization (MR) was performed to verify the causal relationship between top DEGs and NAFLD. The study identified 13 DE-miRNAs and 854 DEGs in the liver between HFrD mice and Chow mice. A Venn diagram revealed that 58 of the predicted target genes of the 13 DE-miRNAs were shared with the DEGs. Finally, 6 DE-miRNAs, 34 DEGs, and 20 predicted lncRNAs were selected to construct the ceRNA regulatory network. The upregulated DEG Clec4e, a target gene of miR-22–5p, was significantly correlated with the risk of NAFLD (OR: 1.41, 95 % CI: 1.04–1.92, <em>P</em> = 0.029) in the MR analysis, and RT-qPCR was applied to validate Clec4e expression in the livers of HFrD mice. Further, the dual-luciferase reporter assay confirmed that miR-22–5p could directly inhibit Clec4e expression by targeting its 3′-UTR. This study identified several novel miRNAs and genes as potential biomarkers of NAFLD. In particular, the miR-22–5p/Clec4e axis is a potential diagnostic target for NAFLD.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"753 ","pages":"Article 151496"},"PeriodicalIF":2.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"TPD52 (isoform 3) promotes resistance to mTOR-targeted inhibitors by regulating c-Myc, PTEN, and direct activation of 4E-BP1 in LNCaP androgen-dependent cells","authors":"Priyanka Khilar , Ramesh Ummanni","doi":"10.1016/j.bbrc.2025.151495","DOIUrl":"10.1016/j.bbrc.2025.151495","url":null,"abstract":"<div><div>A therapeutic strategy targeting the PI3K–AKT–mTOR pathway is widely seen as promising against prostate cancer (PCa) treatment. However, resistance to targeted inhibitors is still a major challenge. Herein we observed that the overexpression of TPD52 (isoform 3) in LNCaP, PCa cells confers resistance to mTOR inhibitors, specifically everolimus and rapamycin. This study demonstrates that TPD52 promotes the proliferation and survival of tumor cells treated with mTOR inhibitors by hyperactivating PI3K/AKT. Despite the inactivation of downstream targets like p70S6K and S6 upon mTOR inhibition, p4E-BP1 remained consistently high in TPD52 overexpressing LNCaP cells, suggesting activation of an alternative regulatory mechanism independent of mTOR. Furthermore, elevated c-Myc levels were correlated with overexpression of TPD52 and were linked to loss of PTEN expression further promoting drug resistance. Contrarily, silencing of TPD52 and c-Myc sensitized LNCaP cells to mTOR inhibitors by restoring PTEN levels and further downregulation of 4E-BP1. Above all, downregulation of both TPD52 and c-Myc enhanced the sensitivity of LNCaP-TPD52 cells facilitating apoptosis indicating a potential strategy to overcome resistance to mTOR inhibitors in PCa. Taken together, these findings underscore the role of TPD52 through c-Myc in conferring resistance to mTOR inhibitors and warrant further exploration of their molecular mechanisms in PCa treatment.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"753 ","pages":"Article 151495"},"PeriodicalIF":2.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiangbo Tong , Yuan Zhao , Yongchao Jin , Zhenyu Hao , Shixin Li , Mei Sun
{"title":"A mini review on the regulation of coagulation homeostasis through interfering with vitamin K-dependent coagula-tion/anticoagulation factors","authors":"Jiangbo Tong , Yuan Zhao , Yongchao Jin , Zhenyu Hao , Shixin Li , Mei Sun","doi":"10.1016/j.bbrc.2025.151494","DOIUrl":"10.1016/j.bbrc.2025.151494","url":null,"abstract":"<div><div>Coagulation disorders, such as excessive bleeding or thrombosis, present significant health challenges. Vitamin K-dependent proteins (VKDPs), including coagulation and anticoagulation factors, are essential for maintaining the coagulation homeostasis due to their key roles in the coagulation cascade. Therefore, VKDPs have become significant targets for regulating coagulation homeostasis, and various strategies have been developed, primarily including small molecule drugs and nanomaterials. This review presents the summary of these strategies, focusing on the mechanisms, effectiveness and limitations. It first discusses the pivotal role of VKDPs in the coagulation cascade, followed by an in-depth analysis of how small molecule drugs and nanomaterials to regulate hemostasis through interfering with VKDPs. Furthermore, this review addresses the challenges faced in the current approaches and potential future research directions. We hope this review will contribute to advancing the development of novel methods for modulating coagulation homeostasis through VKDP interference.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"753 ","pages":"Article 151494"},"PeriodicalIF":2.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mi Jang, Jihye Yang, Dae-Hyun Jeon, Sang Heon Seung, Gene Lee
{"title":"Potential of human dental pulp stem cell-derived conditioned medium for amelo-/odontoblastic differentiation of HERS/ERM cells","authors":"Mi Jang, Jihye Yang, Dae-Hyun Jeon, Sang Heon Seung, Gene Lee","doi":"10.1016/j.bbrc.2025.151490","DOIUrl":"10.1016/j.bbrc.2025.151490","url":null,"abstract":"<div><div>HERS/ERM cells constitute the only dental epithelial population that can be isolated from adult human teeth. Although HERS/ERM cells are the most studied dental epithelial cell source, information on their differentiation is lacking: these cells have a long induction period and low mineralization without coculture with dental mesenchymal stem cells. To characterize and develop an effective method for differentiating dental epithelial cells, we observed the epithelial‒mesenchymal interaction effects of deciduous dental pulp stem cell (dDPSC)-derived conditioned media (CM) during HERS/ERM cell differentiation. The collected CM was freeze-dried (DCM) and applied at high concentrations to determine the optimal concentration. The DCM-20 %, DCM-40 %, DCM-60 %, and DCM-80 % (<em>v</em>/<em>v</em>) groups presented an increased growth pattern. On day 2, increased expression of <em>AMELX</em> was detected in the DCM-60 % and DCM-80 % groups. <em>ENAM</em> expression was increased in the DCM-80 % group on day 2 and in the DCM-treated groups on day 4. In the DCM-80 % group, <em>DSPP</em> expression was significantly increased. In the DCM-60 % and DCM-80 % groups, high DSPP expression was detected. The ENAM expression in the DCM-80 % group was higher than that in the other groups. Mineralized nodules were detected on day 8 in the DCM-40 %, DCM-60 %, and DCM-80 % groups. The amount of calcium deposits increased with increasing DCM concentration. Our data indicated that dDPSC-CM has significant potential to induce ameloblastic and odontoblastic differentiation in HERS/ERM cells. The paracrine factors of dDPSC-CM could induce ameloblast differentiation without direct cell-to-cell interactions. These findings emphasize the potential of dDPSC-CM in the differentiation of HERS/ERM cells in vitro.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"752 ","pages":"Article 151490"},"PeriodicalIF":2.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brian Imbiakha , Shahrzad Ezzatpour , David W. Buchholz , Suresh Poosala , Bharadwaja Vadloori , Akshay Sonawane , Saimatha Gannabathula , Ramya V V S , Nikita Narayan Naik , Shanmugapriya Shanmugasundaram , Sudarsana Reddy Lokireddy , Sridhar Rao Kunchala , Chennakesavulu Thummadi , Pratyusha Godavarty , Kranti Meher , Subrahmanyam Vangala , Uday Saxena , Hector C. Aguilar , Avery August , Julie Sahler
{"title":"Novel nanobody drug conjugate as a prophylactic or therapeutic against SARS-CoV-2 infection in mice","authors":"Brian Imbiakha , Shahrzad Ezzatpour , David W. Buchholz , Suresh Poosala , Bharadwaja Vadloori , Akshay Sonawane , Saimatha Gannabathula , Ramya V V S , Nikita Narayan Naik , Shanmugapriya Shanmugasundaram , Sudarsana Reddy Lokireddy , Sridhar Rao Kunchala , Chennakesavulu Thummadi , Pratyusha Godavarty , Kranti Meher , Subrahmanyam Vangala , Uday Saxena , Hector C. Aguilar , Avery August , Julie Sahler","doi":"10.1016/j.bbrc.2025.151480","DOIUrl":"10.1016/j.bbrc.2025.151480","url":null,"abstract":"<div><div>The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, resulted in global health and economic crisis at an exceptional level. The high transmissibility of SARS-CoV-2, a lack of population immunity, and the prevalence of severe clinical outcomes created a need for the rapid development of effective therapeutic countermeasures. Sybodies, or synthetic nanobodies, are a novel and unique class of synthetic antigen-binding fragments ideal for large-scale production. We created a neutralizing sybody directed against the receptor-binding domain (RBD) epitope of the Spike protein of SARS-CoV-2 and conjugated it to remdesivir to create nanobody-drug-conjugate (NDC). We used a mouse model of infection to determine the capacity of the NDC to reduce disease severity and mortality. K18-hACE2 mice treated with NDC prior to, simultaneously with, and/or post-SARS-CoV-2 infection had reduced weight loss, mortality, lung pathology, and viral RNA in their lungs. This protection was found to be dependent on the protein structure of the sybody. Delivery of these novel therapeutic NDCs through nasal inhalation using a nebulizer could offer a convenient method for patients to self-administer treatments or as a prophylaxis. This platform therapy could apply to new variants of the ongoing SARS-CoV-2 epidemics, or to other pathogens of future pandemic potential.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"753 ","pages":"Article 151480"},"PeriodicalIF":2.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}