BiochimiePub Date : 2025-02-01DOI: 10.1016/j.biochi.2024.10.014
Shikun Ge , Mei Dang , Alberto Carlos Pires Dias , Xiaoying Zhang
{"title":"Engineered IgG Fc-conjugation prolongs the half-life of florfenicol and alleviates pneumonia in mice","authors":"Shikun Ge , Mei Dang , Alberto Carlos Pires Dias , Xiaoying Zhang","doi":"10.1016/j.biochi.2024.10.014","DOIUrl":"10.1016/j.biochi.2024.10.014","url":null,"abstract":"<div><div>Small molecule drugs often exhibit short half-lives, requiring frequent administrations to maintain therapeutic concentrations over an extended period. To address this issue, the fragment crystallizable (Fc) region of IgG, known to prolong the half-life of antibodies via its interaction with the Fc neonatal receptor, was harnessed as a carrier protein to extend the half-life of a small molecule drug, florfenicol. Florfenicol, was chemically coupled to a recombinant Fc protein expressed using the eukaryotic expression system in HEK293 cells. The Fc-florfenicol conjugate exhibited a substantially prolonged half-life of from 3.8 to 9.1 h compared to unconjugated florfenicol and demonstrated excellent therapeutic properties in treating pneumonia in a mouse model. Our results, combined with the literature analysis on Fc-small molecule conjugates, show that Fc can substantially enhance the drug's half-life and suggest the potential for its use as a carrier in novel delivery systems.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 105-113"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482918","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}
BiochimiePub Date : 2025-02-01DOI: 10.1016/j.biochi.2024.10.001
Reyna L. Cuachirria-Espinoza , Alin García-Miranda , Rafael Hernández-Barragán, Dania A. Nava-Tapia, Monserrat Olea-Flores, Napoleón Navarro-Tito
{"title":"Analysis of the relationship between resistin with prognosis, cell migration, and p38 and ERK1/2 activation in breast cancer","authors":"Reyna L. Cuachirria-Espinoza , Alin García-Miranda , Rafael Hernández-Barragán, Dania A. Nava-Tapia, Monserrat Olea-Flores, Napoleón Navarro-Tito","doi":"10.1016/j.biochi.2024.10.001","DOIUrl":"10.1016/j.biochi.2024.10.001","url":null,"abstract":"<div><div>Obesity increases the risk and mortality of breast cancer through dysregulated secretion of proinflammatory cytokines and tumor adipokines that induce an inflammatory breast microenvironment. Resistin is an adipokine secreted by adipocytes, immune cells, and predominantly macrophages, which contributes to cancer progression, but its molecular mechanism in cancer is not completely described. In this study, we analyzed the relationship of resistin on breast cancer prognosis and tumor progression and the effect <em>in vitro</em> of resistin on p38 and ERK1/2 activation in breast cancer cell lines. By bioinformatic analysis, we found that resistin is overexpressed in the basal subtype triple-negative breast cancer and is related to poor prognosis. In addition, we demonstrated a positive correlation between <em>RETN</em> and <em>MAPK3</em> expression in basal triple-negative breast cancer. Importantly, we found amplifications of the <em>RETN</em> gene in at least 20 % of metastatic samples from patients with breast cancer. Most samples with <em>RETN</em> amplifications metastasized to bone and showed high expression of IL-8 (<em>CXCL8</em>) and IL-6 (<em>IL6</em>). Finally, resistin could be considered a prognostic marker for basal triple-negative breast cancer, and we also proposed the possibility that resistin-induced cell migration involves the activation of MAPK in breast cancer cells.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 19-29"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382734","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}
BiochimiePub Date : 2025-02-01DOI: 10.1016/j.biochi.2024.10.003
Sousan Cheong , Yujie Peng , Feng Lu, Yunfan He
{"title":"Structural extracellular matrix-mediated molecular signaling in wound repair and tissue regeneration","authors":"Sousan Cheong , Yujie Peng , Feng Lu, Yunfan He","doi":"10.1016/j.biochi.2024.10.003","DOIUrl":"10.1016/j.biochi.2024.10.003","url":null,"abstract":"<div><div>The extracellular matrix (ECM) is a complex, non-cellular network of molecules that offers structural support for cells and tissues. The ECM is composed of various structural components, including collagen, fibronectin, laminin, perlecan, nidogen, tenascin, and fibulin, which are capable of binding to each other and to cell-to-adhesion receptors, endowing the ECM with unique physical and biochemical properties that are essential for its function in maintaining health and managing disease. Over the past three decades, extensive research has shown that the core of the ECM can significantly impact cellular events at the molecular level. Structural modifications have also been strongly associated with tissue repair. Through interactions with cells, matrix proteins regulate critical processes such as cell proliferation and differentiation, migration, and apoptosis, essential for maintaining tissue homeostasis, formation, and regeneration. This review emphasizes the interlocking networks of ECM macromolecules and their primary roles in tissue regeneration and wound repair. Through studying ECM dynamics, researchers have discovered molecular signaling pathways that demonstrate how the ECM influences protein patterns and open up more possibilities for developing therapeutics that target the ECM to enhance wound repair and tissue regeneration.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 58-68"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382736","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}
BiochimiePub Date : 2025-02-01DOI: 10.1016/j.biochi.2024.10.010
Shuyue Zhu , Chunjie Hu , Yan Wang , Mengli Jin , Qiuyue Zhang , Shaoyu Han , Yating Tang , Desheng Wu , Di Fu , Shuang Jiang , Danning Song , Lin Wei , Wu Song , Chi Zhang , Wenfeng Zhang
{"title":"Daphnetin weakened the pathogenicity of methicillin-resistant Staphylococcus aureus by inhibiting Sortase A and α-hemolysin","authors":"Shuyue Zhu , Chunjie Hu , Yan Wang , Mengli Jin , Qiuyue Zhang , Shaoyu Han , Yating Tang , Desheng Wu , Di Fu , Shuang Jiang , Danning Song , Lin Wei , Wu Song , Chi Zhang , Wenfeng Zhang","doi":"10.1016/j.biochi.2024.10.010","DOIUrl":"10.1016/j.biochi.2024.10.010","url":null,"abstract":"<div><div>The increasing prevalence of antibiotic-resistant bacteria, represented by Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA), has necessitated a shift towards anti-virulence strategies in treatment approaches. This research demonstrated that daphnetin effectively disrupted MRSA virulence by targeting Sortase A (SrtA), an enzyme in <em>Staphylococcus aureus</em> (<em>S. aureus</em>) responsible for adhesion and invasion, as well as the toxin <em>α</em>-hemolysin (Hla) that leads to cell lysis. Utilizing Fluorescence Resonance Energy Transfer, daphnetin showed direct inhibitory effect on SrtA activity, with an IC<sub>50</sub> of 25.98 μg/mL. Additionally, daphnetin hindered various SrtA-mediated processes in <em>S. aureus</em>, such as fibronectin adherence, A549 cell invasion, biofilm formation, and bacterial motility. Daphnetin inhibited <em>S. aureus</em>-induced hemolysis and reduced Hla expression as confirmed by Western blot analysis. Molecular docking studies identified specific binding sites of daphnetin with SrtA, highlighting key amino acid residues like GLU-77, TYR-75, and LYS-145, with a docking score of −7.139 kcal/mol. Besides that, daphnetin exhibited a protective effect on MRSA-induced pneumonia <em>in vivo</em>. In summary, daphnetin, a natural compound, effectively inhibited SrtA and Hla activities, attenuating MRSA virulence and showcasing potential for treating bacterial infections.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 84-94"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482917","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":"Enzymatic tools for mitochondrial genome manipulation","authors":"Beatrisa Rimskaya , Nikita Shebanov , Nina Entelis , Ilya Mazunin","doi":"10.1016/j.biochi.2024.10.013","DOIUrl":"10.1016/j.biochi.2024.10.013","url":null,"abstract":"<div><div>Mutations in mitochondrial DNA (mtDNA) can manifest phenotypically as a wide range of neuromuscular and neurodegenerative pathologies that are currently only managed symptomatically without addressing the root cause. A promising approach is the development of molecular tools aimed at mtDNA cutting or editing. Unlike nuclear DNA, a cell can have hundreds or even thousands of mitochondrial genomes, and mutations can be present either in all of them or only in a subset. Consequently, the developed tools are aimed at reducing the number of copies of mutant mtDNA or editing mutant nucleotides. Despite some progress in the field of mitochondrial genome editing in human cells, working with model animals is still limited due to the complexity of their creation. Furthermore, not all existing editing systems can be easily adapted to function within mitochondria. In this review, we evaluate the mtDNA editing tools available today, with a particular focus on specific mtDNA mutations linked to hereditary mitochondrial diseases, aiming to provide an in-depth understanding of both the opportunities and hurdles to the development of mitochondrial genome editing technologies.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 114-128"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482919","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}
BiochimiePub Date : 2025-02-01DOI: 10.1016/j.biochi.2024.09.016
Aleksandra V. Sen'kova , Ali Bishani , Innokenty A. Savin , Marina A. Zenkova , Elena L. Chernolovskaya
{"title":"Effect of immunostimulatory RNA on the fibrosis development in Bleomycin- or LPS-induced mouse models","authors":"Aleksandra V. Sen'kova , Ali Bishani , Innokenty A. Savin , Marina A. Zenkova , Elena L. Chernolovskaya","doi":"10.1016/j.biochi.2024.09.016","DOIUrl":"10.1016/j.biochi.2024.09.016","url":null,"abstract":"<div><div>Previously, we described a 19-base pair double-stranded RNA with 3′-trinucleotide overhangs, acting as immunostimulatory RNA (isRNA). This molecule demonstrated notable antiproliferative effects on cancer cells, inhibited tumor growth, and elicited immunostimulatory and antiviral responses by inducing cytokine and interferon production. Within this study, we compared the efficiency of lung fibrosis development, initiated in mice by BLM or LPS using different schemes of induction. Then we compared the effect of isRNA used in a preventive or therapeutic regimen on the development of fibrosis in selected BLM- and LPS-induced mouse models and showed that isRNA can be used in pathological conditions accompanied by the development of inflammation and the risk of fibrosis formation, without adverse side effects. Prophylactic regimen of isRNA application is beneficial for prevention of the development of pulmonary fibrosis.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 9-18"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373751","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}
BiochimiePub Date : 2025-02-01DOI: 10.1016/j.biochi.2024.10.004
Gabriel Principe , Virginia Lezcano , Silvina Tiburzi , Alicia B. Miravalles , Betina N. García , Fernanda Gumilar , Verónica González-Pardo
{"title":"In vitro and in vivo evidence of the antineoplastic activity of quercetin against endothelial cells transformed by Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor","authors":"Gabriel Principe , Virginia Lezcano , Silvina Tiburzi , Alicia B. Miravalles , Betina N. García , Fernanda Gumilar , Verónica González-Pardo","doi":"10.1016/j.biochi.2024.10.004","DOIUrl":"10.1016/j.biochi.2024.10.004","url":null,"abstract":"<div><div>Quercetin (QUE) is a natural flavonoid with well-known anticancer capabilities, although its effect on viral-induced cancers is less studied. Kaposi's sarcoma (KS) is a viral cancer caused by the human herpesvirus-8, which, during its lytic phase, expresses a constitutively activated viral G protein-coupled receptor (vGPCR) able to induce oncogenic modifications that lead to tumor development. The aim of this work was to investigate the potential effect of QUE on <em>in vitro</em> and <em>in vivo</em> models of Kaposi's sarcoma, developed by transforming endothelial cells with the vGPCR of Kaposi's sarcoma-associated herpesvirus. Initially, the antiproliferative effect of QUE was determined in endothelial cells stably expressing the vGPCR (vGPCR cells), with an IC50 of 30 μM. Additionally, QUE provoked a decrease in vGPCR cell viability, interfered with the cell cycle progression, and induced apoptosis, as revealed by annexin V/PI analysis and caspase-3 activity. The presence of apoptotic bodies and disorganized actin filaments was observed by SEM and phalloidin staining. Furthermore, tumors from vGPCR cells were induced in nude mice, which were treated with QUE (50 or 100 mg/kg/d) resulting in retarded tumor progression and reduced tumor weight. Notably, neither kidney nor liver damage was observed, as indicated by biochemical parameters in serum. In conclusion, this study suggests for the first time that QUE exhibits antineoplastic activity in both <em>in vitro</em> and <em>in vivo</em> models of KS, marking a starting point for further investigations and protocols for therapeutic purpose.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 30-41"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382735","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}
BiochimiePub Date : 2025-02-01DOI: 10.1016/j.biochi.2024.10.016
Sabita Rangra, Kamal Krishan Aggarwal
{"title":"Characterization and kinetics of a cathepsin B-inhibiting protein from Musa acuminata Colla peel","authors":"Sabita Rangra, Kamal Krishan Aggarwal","doi":"10.1016/j.biochi.2024.10.016","DOIUrl":"10.1016/j.biochi.2024.10.016","url":null,"abstract":"<div><div>Hyperexpression of cathepsin B caused by an imbalance of endogenous inhibitors is involved in multiple pathologies, hence making it a key therapeutic target. Protease inhibitors are effective biomolecules that regulate protease activities and are considered potential therapeutic agents in various diseases. Plant protease inhibitors have been reported as an effective complementary alternative drug. A proteinaceous cathepsin B inhibitor (CBI-BP) has been isolated from <em>Musa acuminata</em> Colla (banana) peel with a molecular weight of 27.9 kDa on SDS-PAGE. The purity of the CBI-BP was confirmed on the native- PAGE. The isolated CBI-BP showed an IC<sub>50</sub> value of 8.14 μg and a K<sub>i</sub> value of 10.59 μg (0.19 μM). Cathepsin B inhibition kinetics indicated that CBI-BP follows a mixed-type of cathepsin B inhibition. Its inhibition activity was also confirmed by reverse zymography. The inhibitor was stable from pH 2.6–10.0 with maximum activity at pH 7.2, temperature 25–100 °C and exhibited thermostability for 60 min at 70 °C. MALDI/TOF/MS analysis of CBI-BP showed 40 % similarity to the GH18 domain-containing protein (A0A4S8JRM9) from <em>Musa balbisiana.</em> Although <em>in-silico</em> docking studies showed binding of A0A4S8JRM9 to cathepsin B affects the binding energy of the substrate to cathepsin B but is not reported for any anti-cathepsin B activity. This suggests that isolated CBI-BP might be a novel protein with anti-cathepsin B activity. Thus the isolated CBI-BP may be further explored as possible anti-cathepsin B drug.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 141-150"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514568","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}