IF 3.3 3区生物学

Biochimie Pub Date : 2025-05-17 DOI: 10.1016/j.biochi.2025.05.006

Ana F. Gómez Garay , Jorge J. Alfonso , Aleff F. Francisco , Erika C.S. Araújo , Marcos R.M. Fontes , Carlos A.H. Fernandes , Soraya S. Pereira , Anderson M. Kayano , Leonardo A. Calderon , Jamile M. Macedo , Mateus F. Souza , Rudson J. Holanda , Juliana C. Sobrinho , Andreimar M. Soares

{"title":"Structural and kinetic profiling of Leishmania braziliensis trypanothione reductase: A molecular model for the development of targeted therapies","authors":"Ana F. Gómez Garay , Jorge J. Alfonso , Aleff F. Francisco , Erika C.S. Araújo , Marcos R.M. Fontes , Carlos A.H. Fernandes , Soraya S. Pereira , Anderson M. Kayano , Leonardo A. Calderon , Jamile M. Macedo , Mateus F. Souza , Rudson J. Holanda , Juliana C. Sobrinho , Andreimar M. Soares","doi":"10.1016/j.biochi.2025.05.006","DOIUrl":"10.1016/j.biochi.2025.05.006","url":null,"abstract":"<div><div>This study explores the recombinant protein expression, purification, and characterization of <em>Leishmania braziliensis</em> Trypanothione Reductase (<em>Lb</em>TR), an essential enzyme implicated in cutaneous leishmaniasis. Using <em>E. coli</em> as the host organism, the synthetic gene encoding <em>Lb</em>TR was successfully expressed and subsequently purified using Immobilized Metal Affinity Chromatography (IMAC) yielding 20 mg/L of highly pure <em>Lb</em>TR, verified by SDS-PAGE and isoelectric focusing. Comprehensive biochemical analyses were conducted to determine the recombinant enzyme's kinetic properties and structural features. Enzymatic assays revealed that <em>Lb</em>TR efficiently reduces its natural substrate, following Michaelis-Menten kinetics. Structural characterization, including dynamic light scattering and fluorescence spectroscopy, confirmed the protein's stability and homogeneity in solution under varying temperatures. Circular dichroism analysis corroborated the presence of significant α-helical and β-sheet content, aligning with the structural model generated with AlphaFold. Molecular dynamics simulations over 1 μs were employed to investigate the conformational dynamics of <em>Lb</em>TR in its native homodimeric form, complexed with essential cofactors and substrates. The results from these simulations offer valuable insights into the enzyme's structural behavior and catalytic mechanism, underscoring its potential as a target for therapeutic development against leishmaniasis.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"235 ","pages":"Pages 14-28"},"PeriodicalIF":3.3,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103284","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}

引用次数: 0

Inside front cover-EDB 内部前盖- edb

IF 3.3 3区生物学

Biochimie Pub Date : 2025-05-17 DOI: 10.1016/S0300-9084(25)00087-2

引用次数: 0

Caffeine modulates immunoproteasome activity and content in colorectal adenocarcinoma cells 咖啡因调节大肠癌细胞中免疫蛋白酶体的活性和含量。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-05-09 DOI: 10.1016/j.biochi.2025.05.004

Alexander Burov , Alexander Rezvykh , Valeria Vedernikova , Alexey Belogurov Jr. , Vladimir Prassolov , Pavel Spirin , Sergey Funikov , Alexey Morozov , Vadim Karpov

{"title":"Caffeine modulates immunoproteasome activity and content in colorectal adenocarcinoma cells","authors":"Alexander Burov , Alexander Rezvykh , Valeria Vedernikova , Alexey Belogurov Jr. , Vladimir Prassolov , Pavel Spirin , Sergey Funikov , Alexey Morozov , Vadim Karpov","doi":"10.1016/j.biochi.2025.05.004","DOIUrl":"10.1016/j.biochi.2025.05.004","url":null,"abstract":"<div><div>Proteasomes hydrolyze most intracellular proteins. Immunoproteasome is a form of proteasome implicated in inflammation, cancer and autoimmune diseases. Modulation of immunoproteasome activity is a promising approach against several pathologies. Using previously obtained reporter colorectal cancer cell lines, we tested how commonly used compounds including ibuprofen, acetylsalicylic acid, vitamin C, caffeine and others, affect immunoproteasome expression. Flow cytometry, qPCR and Western blot were used to evaluate immunoproteasome subunit expression. Proteasome activity was tested using fluorogenic substrates and the activity-based probe. Transcriptome analysis was performed to identify patterns of gene expression changes. Interestingly, caffeine was the only drug that stimulated modest reduction in quantity of immunoproteasomes. The effect of caffeine varied between cell lines and was stronger as a result of prolonged treatment. The reduction of immunoproteasome content in cells coincided with decreased expression of immunoproteasome subunits, genes encoding the Nrf3 transcription factor and a PAC4 proteasome assembly chaperone, as well as the reduced levels of oxidative stress. Caffeine did not affect the degradation of immunoproteasomes by autophagy. Obtained results uncover novel biological effects of caffeine, our data might help to optimize existing and develop new strategies for the treatment of colorectal cancer and several autoimmune diseases.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"235 ","pages":"Pages 1-13"},"PeriodicalIF":3.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045938","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}

引用次数: 0

Unveiling the molecular basis of hygienic behavior in Apis cerana indica through antennal proteomics 利用触角蛋白质组学揭示中华蜜蜂卫生行为的分子基础

IF 3.3 3区生物学

Biochimie Pub Date : 2025-05-06 DOI: 10.1016/j.biochi.2025.05.002

Ramkumar Haran , Chakkarai Sathyaseelan , Ettiappan Sumathi , Sundaravadivel Sathiya Priya , Muthusamy Gayathri , Ravichandran Prathiksha , Ganeshan Shandeep , Mannu Jayakanthan

{"title":"Unveiling the molecular basis of hygienic behavior in Apis cerana indica through antennal proteomics","authors":"Ramkumar Haran , Chakkarai Sathyaseelan , Ettiappan Sumathi , Sundaravadivel Sathiya Priya , Muthusamy Gayathri , Ravichandran Prathiksha , Ganeshan Shandeep , Mannu Jayakanthan","doi":"10.1016/j.biochi.2025.05.002","DOIUrl":"10.1016/j.biochi.2025.05.002","url":null,"abstract":"<div><div>Hygienic behavior in honey bees, particularly <em>Apis cerana indica</em>, is essential for the health of the colony as it helps reduce the impact of diseases and parasites. Despite its importance, the underlying molecular mechanisms remain inadequately characterized. Using a label-free quantitative proteomics method, this study investigates the antennal proteome associated with hygienic behavior. We employed Principal Component Analysis, Partial Least Squares Discriminant Analysis, and RT-qPCR to identify significant proteins that are involved in this behavior. Our analysis identified 408 proteins in colonies demonstrating high hygienic behavior and 419 proteins in those with low hygienic behavior, with 219 proteins showing significant differences in abundance. Notably, several odorant-binding proteins were upregulated in high-hygiene colonies. Furthermore, pathway enrichment analysis revealed that RNA transport and various signaling pathways are involved in this behavioral trait. The protein-protein interaction analysis illustrated substantial clustering among the odorant-binding proteins, underscoring their critical role in the mechanisms underlying hygienic behavior. This research enhances our understanding of the molecular basis of hygienic behavior in <em>Apis cerana indica</em>, positioning odorant-binding proteins as potential biomarkers for further studies that aim at improving colony health and resilience against pests and diseases.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"234 ","pages":"Pages 110-119"},"PeriodicalIF":3.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931825","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}

引用次数: 0

Inside front cover-EDB 内部前盖- edb

IF 3.3 3区生物学

Biochimie Pub Date : 2025-04-25 DOI: 10.1016/S0300-9084(25)00070-7

引用次数: 0

Exploring the role of G-quadruplex DNA, and their structural polymorphism, in targeting small molecules for the design of anticancer therapeutics: Progress, challenges, and future directions 探索g -四重体DNA及其结构多态性在靶向小分子抗癌药物设计中的作用：进展、挑战和未来方向

IF 3.3 3区生物学

Biochimie Pub Date : 2025-04-17 DOI: 10.1016/j.biochi.2025.04.004

Soma Roy , Pulakesh Pramanik , Santanu Bhattacharya

引用次数: 0

Kyasanur Forest disease virus non-structural protein NS1 forms multimers in solution, with a distinctly identifiable tetrameric state 森林疫病病毒非结构蛋白NS1在溶液中形成多聚体，具有明显可识别的四聚体状态

IF 3.3 3区生物学

Biochimie Pub Date : 2025-04-17 DOI: 10.1016/j.biochi.2025.04.005

Rohit Gupta , Shruti Sharma , Anjali Saroj , Rishav Madhukalya , Vivek Kumar , Vidushi Agarwal , Dilip Kumar , Vidya Mangala Prasad , Rajesh Kumar

{"title":"Kyasanur Forest disease virus non-structural protein NS1 forms multimers in solution, with a distinctly identifiable tetrameric state","authors":"Rohit Gupta , Shruti Sharma , Anjali Saroj , Rishav Madhukalya , Vivek Kumar , Vidushi Agarwal , Dilip Kumar , Vidya Mangala Prasad , Rajesh Kumar","doi":"10.1016/j.biochi.2025.04.005","DOIUrl":"10.1016/j.biochi.2025.04.005","url":null,"abstract":"<div><div>Kyasanur Forest Disease Virus (KFDV), a flavivirus, is predominantly present in the tropical region of southern India and is responsible for viral hemorrhagic disease in primates and non-primate animals. KFDV infection is spread by tick bites. The other medically important viruses of Flaviviridae family are dengue (DENV), Zika (ZIKV), West Nile virus (WNV) and Japanese encephalitis virus (JEV). The flaviviruses are collectively responsible for diverse disease pathologies and account for a major global health burden. A major contributing factor to disease pathogenesis of flavivirus is the secreted form of non-structural protein 1 (NS1). However, <em>in vivo</em> studies using lethal flavivirus challenge have demonstrated the protective role of NS1-specific antibodies and complement the hypothesis to explore possibilities of NS1-based vaccine and therapeutic candidates. Recent structural studies on DENV, ZIKV, JEV and WNV NS1 antigen have shown that the sNS1 protein exists in high-order oligomeric states. However, structural insights about the high-order oligomeric states of sNS1 of tick-borne flaviviruses and their biological significance are poorly explored. In this study, we have expressed and purified the KFDV NS1 protein in the mammalian expression system. The KFDV sNS1 protein exhibits higher oligomeric conformation in solution as determined by size exclusion chromatography (SEC), and negative stain transmission electron microscopy (NS-TEM). Single-particle analysis of KFDV NS1 reveals tetrameric arrangements that are structurally similar to previously reported NS1 structures from other flaviviruses. Our study will help to develop a future roadmap of the rational design of broad-spectrum anti-NS1 antibodies and subunit vaccines effective against tick-borne flaviviruses.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"234 ","pages":"Pages 89-94"},"PeriodicalIF":3.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876525","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}

引用次数: 0

Human prostacyclin and thromboxane synthases: Molecular interactions, regulation, and pharmacology 人前列环素和凝血素合成酶：分子相互作用、调控和药理学

IF 3.3 3区生物学

Biochimie Pub Date : 2025-04-11 DOI: 10.1016/j.biochi.2025.04.003

Pavel V. Ershov, Evgeniy O. Yablokov, Yuri V. Mezentsev, Alexis S. Ivanov

{"title":"Human prostacyclin and thromboxane synthases: Molecular interactions, regulation, and pharmacology","authors":"Pavel V. Ershov, Evgeniy O. Yablokov, Yuri V. Mezentsev, Alexis S. Ivanov","doi":"10.1016/j.biochi.2025.04.003","DOIUrl":"10.1016/j.biochi.2025.04.003","url":null,"abstract":"<div><div>Prostanoids are lipid mediators of the human body that are involved in the inflammation and platelet aggregation. Prostacyclin is a vasodilator and inhibitor of platelet aggregation, and a product of the enzymatic reaction catalyzed by prostacyclin synthase (PTGIS). Thromboxane is a vasoconstrictor and synthesized by thromboxane synthase (TBXAS1). An imbalance of prostanoids can accompany cardio-/cerebrovascular diseases and cancers. PTGIS and TBXAS1 are clinically relevant membrane-bound enzymes of the multigene family of cytochromes P450 (CYPs), also known as CYP8A1 and CYP5A1, respectively. Particular studies of these functional antagonists will contribute to the elucidation of pathogenic mechanisms. The purpose of this work was to analyze the literature landscape over a period of 2020–2024 in the field of biological, pharmacogenomic, and pharmacological features of PTGIS and TBXAS1 as well as to explore the potential of their regulation at the post-transcriptional and post-translational levels using systems biological analysis. The review discusses recent findings on the novel aspects of both synthases established in gene knockout and overexpression experiments, current preclinical pharmacology, and potential ways of gene expression regulation. Identification of protein-protein interactions and post-translational modifications appear to be the main options for modulating PTGIS and TBXAS1 activity. The microsomal CYPs are known to form complexes with each other and direct interactions of CYP2E1 with both synthases can probably lead to modulation of their activity. Progress in the preclinical development of low molecular weight compounds as inhibitors of TBXAS1 is more prospective than PTGIS that is applied as gene therapy biologicals for <em>in vivo</em> production of prostacyclin due to its noticeable anticancer and vasodilator effects.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"234 ","pages":"Pages 76-88"},"PeriodicalIF":3.3,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850467","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}

引用次数: 0

Phenotypic changes associated with continuous long term in vitro expansion of bone marrow-derived mesenchymal stem cells 与骨髓间充质干细胞体外连续长期扩增相关的表型变化

IF 3.3 3区生物学

Biochimie Pub Date : 2025-04-08 DOI: 10.1016/j.biochi.2025.04.002

Vitali V. Maldonado , Hanna Jensen , C. Lowry Barnes , Rebekah M. Samsonraj

{"title":"Phenotypic changes associated with continuous long term in vitro expansion of bone marrow-derived mesenchymal stem cells","authors":"Vitali V. Maldonado , Hanna Jensen , C. Lowry Barnes , Rebekah M. Samsonraj","doi":"10.1016/j.biochi.2025.04.002","DOIUrl":"10.1016/j.biochi.2025.04.002","url":null,"abstract":"<div><div>In vitro expansion of mesenchymal stem cells is necessary to obtain a higher cell number for clinical applications. However, long-term expansion can produce significant phenotypic changes on these cells, decreasing their therapeutic utility. Therefore, understanding the phenotypic changes that long-term expansion triggers in mesenchymal stem cells will allow for better and more consistent cell therapy results. Here, we evaluate the phenotypic changes caused by continuous passaging through colony forming unit-fibroblast assay, senescence beta-galactosidase staining, morphology examination, secretome analysis, surface marker expression, protein quantification, osteogenic and adipogenic differentiation, and CD4<sup>+</sup> T lymphocyte immunosuppressive potential. Long-term in vitro culture decreases mesenchymal stem cell osteogenic potential and self-renewal, increases cell size, and senescence, but does not consistently affect adipogenic differentiation. Surface marker expression remains similar for positive and negative markers, while secretory phenotype shifts with decreased p14ARF, MMP-3, p21 Waf1/Cip1,ENA-78, GCP-2, GROα, IL-3, IL-7, IL-8, RANTES, TNFβ, and VEGF-A expression, and increased p53, p16 INK4a, MCP-1, and SDF-1 expression. Immunomodulatory potential remains unchanged. These findings can help better understand the phenotypic changes that mesenchymal stem cells undergo while expanded in vitro.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"234 ","pages":"Pages 62-75"},"PeriodicalIF":3.3,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848046","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}

引用次数: 0

Transcriptomic analysis of digitoxin: Synergy with doxorubicin in HER2-overexpressing MDA-MB-453 breast cancer cells 洋地黄毒素的转录组学分析：与阿霉素在her2过表达的MDA-MB-453乳腺癌细胞中的协同作用。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-04-04 DOI: 10.1016/j.biochi.2025.04.001

Linda Saxe Einbond , Kunhui Huang , Michael Balick , Hongbao Ma , Rajendra Gharbaran , Stephen Redenti , Hsan-au Wu

{"title":"Transcriptomic analysis of digitoxin: Synergy with doxorubicin in HER2-overexpressing MDA-MB-453 breast cancer cells","authors":"Linda Saxe Einbond , Kunhui Huang , Michael Balick , Hongbao Ma , Rajendra Gharbaran , Stephen Redenti , Hsan-au Wu","doi":"10.1016/j.biochi.2025.04.001","DOIUrl":"10.1016/j.biochi.2025.04.001","url":null,"abstract":"<div><div>The aim of this research is to further elucidate the mechanism of action of digitoxin and explore its potential synergistic effects with doxorubicin. MDA-MB-453 breast cancer cells, characterized by HER2 overexpression and low ER levels, were exposed to digitoxin at three doses (0.1 (0.13 μM), 0.2, and 1.0 μg/ml). RNA was extracted over 6 and 24-h periods to subject to transcriptomic analysis, using IPA software. To validate the findings, cell growth inhibitory, Western blot, and enzymatic assays were performed. In addition, molecular docking was carried out to assess the interaction of digitoxin and doxorubicin with the Na<sup>+</sup>/K<sup>+</sup>-ATPase. IPA analysis indicates that the effects of digitoxin are dose and time-dependent; at the highest dose, digitoxin activates the transcription of cholesterol biosynthetic genes at early times, and the stress response gene <em>ATF3</em> at later times. Key genes at the central point of the pathways altered by digitoxin include: (activated) <em>TP53</em>, <em>CREB1</em>, and <em>TGFB1</em> at the highest dose at 6 and 24 h and (repressed) <em>MYCN</em> at the middle dose at 24 h. <em>ATF3</em> also plays a role in the action of doxorubicin, and digitoxin exhibits synergy with doxorubicin in MDA-MB-453 cells. Molecular docking studies demonstrated binding potential of both digitoxin and doxorubicin to Na<sup>+</sup>/K<sup>+</sup>-ATPase, with doxorubicin showing a stronger binding affinity. Our results highlight the role of bioelectric signaling through ion channel proteins, like Na<sup>+</sup>/K<sup>+</sup>-ATPase, in cancer development. Our findings suggest it is worthwhile to study the use of digitoxin, alone or combined with doxorubicin, for treating estrogen receptor-negative breast cancer, but caution of possible risks to patients who take both drugs in combination.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"234 ","pages":"Pages 95-109"},"PeriodicalIF":3.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797259","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}

引用次数: 0

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