Biochimie最新文献_第5页

Bothropstoxins I and II as potent phospholipase A2 molecules from Bothrops jararacussu to impair hepatitis C virus infection Bothropstoxins I和II是抑制丙型肝炎病毒感染的有效磷脂酶A2分子。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-04-25 DOI: 10.1016/j.biochi.2025.04.006

Carina Machado Pereira , Jacqueline Farinha Shimizu , Natasha Marques Cassani , Igor Andrade Santos , Cintia Bittar , Adélia Cristina Oliveira Cintra , Suely Vilela Sampaio , Mark Harris , Paula Rahal , Ana Carolina Gomes Jardim

{"title":"Bothropstoxins I and II as potent phospholipase A2 molecules from Bothrops jararacussu to impair hepatitis C virus infection","authors":"Carina Machado Pereira , Jacqueline Farinha Shimizu , Natasha Marques Cassani , Igor Andrade Santos , Cintia Bittar , Adélia Cristina Oliveira Cintra , Suely Vilela Sampaio , Mark Harris , Paula Rahal , Ana Carolina Gomes Jardim","doi":"10.1016/j.biochi.2025.04.006","DOIUrl":"10.1016/j.biochi.2025.04.006","url":null,"abstract":"<div><div>Hepatitis C virus (HCV) (now classified <em>Hepacivirus hominis</em>) that infects an estimated 50 million individuals worldwide and causes chronic liver disease. The current treatment for infected patients primarily relies on direct-acting antivirals (DAAs). However, this treatment is marked by its high cost, numerous side effects, and documented instances of antiviral resistance. These challenges underscore the imperative for developing novel therapeutic strategies. In this framework, naturally occurring compounds have exhibited considerable medical significance attributable to their biological functionalities. Compounds extracted from snake venoms have evidenced antiviral efficacy against a variety of viral pathogens including <em>Orthoflavivirus denguei</em> (DENV), <em>Orthoflavivirus flavi</em> (YFV), <em>Orthoflavivirus zikaense</em> (ZIKV), and HCV. Here, the activity of 10 proteins isolated from snakes’ venom of <em>Bothrops</em> genus were evaluated against HCV replicative cycle. JFH-1 HCV system infected Huh-7.5 cell. Cell viability was measured simultaneously through MTT assay. Eight compounds inhibited up to 99 % of HCV infection, with the most potent inhibitory rates observed in BthTX-I and BthTX-II. These exhibited an SI of > 50 and 16,220, respectively, being able to block 84.7 % and 96 % of HCV infectivity. BthTX-II also demonstrated a protective effect in cells treated prior to HCV infection of approximately 86.7 %. Molecular docking calculations suggest interactions between the two proteins with HCV E1E2 glycoprotein complex. BthTX-II exhibited stronger interactions, indicated by 22 hydrophobic interactions. In conclusion, these compounds were shown to inhibit HCV infectivity by either acting on the virus particles or protecting the cells against infection.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"235 ","pages":"Pages 39-48"},"PeriodicalIF":3.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002063","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

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

Divergent ferroptotic pathways in breast cancer cells: IGFBP6-regulated mitochondrial lipid peroxidation under erastin and omega-3 DHA treatment 乳腺癌细胞中不同的铁细胞凋亡途径：igfbp6在erastin和omega-3 DHA处理下调节线粒体脂质过氧化。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-04-01 DOI: 10.1016/j.biochi.2025.03.010

Mariia Silkina , Alexandra Razumovskaya , Timur Kulagin , Artem Fatkulin , Karina Klycheva , Darya Olkhovik , Darya Averinskaya , Oksana Kolodeeva , Olga Kolodeeva , Alexander Tonevitsky , Sergey Nikulin

{"title":"Divergent ferroptotic pathways in breast cancer cells: IGFBP6-regulated mitochondrial lipid peroxidation under erastin and omega-3 DHA treatment","authors":"Mariia Silkina , Alexandra Razumovskaya , Timur Kulagin , Artem Fatkulin , Karina Klycheva , Darya Olkhovik , Darya Averinskaya , Oksana Kolodeeva , Olga Kolodeeva , Alexander Tonevitsky , Sergey Nikulin","doi":"10.1016/j.biochi.2025.03.010","DOIUrl":"10.1016/j.biochi.2025.03.010","url":null,"abstract":"<div><div>Breast cancer remains a major challenge and new therapeutic approaches are needed for its treatment. Ferroptosis is considered a promising alternative cell death mechanism to eliminate resistant cancer cells. In previous works, we identified that lower <em>IGFBP6</em> gene expression in tumor tissue corresponds to a worse prognosis for breast cancer patients and, at the same, time makes them more sensitive to ferroptosis. In this study, we further investigated the mechanism of ferroptosis induction in <em>IGFBP6</em> knockdown and control MDA-MB-231 breast cancer cells by the canonical ferroptosis inducer erastin and omega-3 docosahexaenoic acid (DHA). Our results indicate that there is a significant overlap between the mechanisms of action of both of these molecules, as they regulate the same subset of genes, and their action can be inhibited by canonical ferroptosis inhibitors. On the other hand, we also observed significant differences between the effects of erastin and DHA. The most notable of these are the additional activation of apoptosis-related genes by DHA and its minor peroxidation of mitochondrial lipid membranes. Interestingly, our kinetic analysis of ferroptosis induction showed that <em>IGFBP6</em> knockdown cells began to die earlier and could hardly be rescued from erastin-induced ferroptosis by mitochondrial antioxidant SkQ1, in contrast to control cells. Overall, our data suggest that the action of DHA is less dependent on mitochondrial membrane peroxidation during ferroptosis induction, and this molecule can be a promising candidate for the treatment of breast cancer, especially in the case of reduced <em>IGFBP6</em> gene expression in cancer cells.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"234 ","pages":"Pages 48-61"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782270","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

Enhancing amplification efficiency and reducing molecular diagnostic reaction time through rational design of T4 gp32 Variants in recombinase polymerase amplification 重组酶扩增中T4 gp32变异体的合理设计提高扩增效率，缩短分子诊断反应时间。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-03-28 DOI: 10.1016/j.biochi.2025.03.008

Lin Zhang , Lvping Wu , Yiwei Guo , Enjie Wang , Jiaxing Zhang , Shengping You , Rongxin Su , Wei Qi

{"title":"Enhancing amplification efficiency and reducing molecular diagnostic reaction time through rational design of T4 gp32 Variants in recombinase polymerase amplification","authors":"Lin Zhang , Lvping Wu , Yiwei Guo , Enjie Wang , Jiaxing Zhang , Shengping You , Rongxin Su , Wei Qi","doi":"10.1016/j.biochi.2025.03.008","DOIUrl":"10.1016/j.biochi.2025.03.008","url":null,"abstract":"<div><div>Recombinase polymerase amplification (RPA) is a prominent isothermal nucleic acid amplification method widely applied in molecular diagnostics. The stability and functionality of the single-stranded DNA-binding protein T4 gene 32 (gp32) crucial for pre-synaptic filament formation and D-loop stabilization, play a key role in determining RPA efficiency. In this study, V62C/T80C and Y186R mutants with improved performance were screened by rational disulfide bond construction and virtual saturation mutagenesis, respectively. The structural changes in V62C/T80C and the altered ssDNA-binding capacity in Y186R both contribute to RPA amplification by enhancing the formation of UvsX-ssDNA presynaptic filaments and stabilizing the D-loop structure during homologous recombination, respectively. The two mutants each demonstrated unique advantages in the RPA process. V62C/T80C significantly accelerates the amplification process, reducing the RPA reaction time by 47 %, while Y186R showed a 123 % increase in efficiency across the entire amplification cycle. Totally, this study applied a rational strategy on gp32 optimization, shortening RPA reaction times, enhancing the RPA reaction efficiency, and advancing its application in clinical and point-of-care diagnostics.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"234 ","pages":"Pages 1-9"},"PeriodicalIF":3.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756501","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

Molecular and biochemical approaches of the trypanothione system in Leishmania spp.: A key player in parasite resistance to antimonial therapy 利什曼原虫中锥虫硫酮系统的分子和生化研究：对抗疟治疗产生抗性的关键因素。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-03-25 DOI: 10.1016/j.biochi.2025.03.007

Geovane Dias-Lopes , Sara Maria Xavier Cruz , Bernardo Acácio Santini Pereira , Anabel Zabala-Peñafiel , Carlos Roberto Alves

{"title":"Molecular and biochemical approaches of the trypanothione system in Leishmania spp.: A key player in parasite resistance to antimonial therapy","authors":"Geovane Dias-Lopes , Sara Maria Xavier Cruz , Bernardo Acácio Santini Pereira , Anabel Zabala-Peñafiel , Carlos Roberto Alves","doi":"10.1016/j.biochi.2025.03.007","DOIUrl":"10.1016/j.biochi.2025.03.007","url":null,"abstract":"<div><div>The trypanothione system is a crucial antioxidant defense mechanism in <em>Leishmania</em> spp. The enzymes involved, including trypanothione reductase (TR), trypanothione synthetase (TS), tryparedoxin (TXN) and tryparedoxin peroxidase (TXNPx) are essential for maintaining the redox balance. This system plays a fundamental role in the biology of <em>Leishmania</em> spp., contributing to parasite resistance against metalloid-based treatments, such as trivalent antimony (Sb<sup>3+</sup>). The mechanisms underlying this resistance, particularly those linked to the functionality of the trypanothione system, have garnered increasing interest. This review prioritizes studies conducted with clinical isolates of <em>Leishmania</em> spp. that evaluated gene expression, protein abundance, and enzyme activity to determine how variations in trypanothione-related mechanisms influence their clinical outcomes. Additionally, complementary strategy involving different protocols to determine intracellular non-protein thiols have further enrich the information into these studies. Notably, the evidence gathered here highlights that studies have focused on only four <em>Leishmania</em> spp. with just one belonging to the <em>Viannia</em> subgenus. Several approaches have been used to determine TR and TXNPx enzyme activity in parasite lysates, supporting their use as tools for studying resistant phenotypes. Additionally, the assessment of TR, TXNPx and TS activities has been applied in kinetic studies for screening of inhibitor compounds. The functional insights presented herein may aid in elucidating the basis of parasite resistance and guide the development of more effective therapeutic strategies against leishmaniasis in its different clinical forms.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"234 ","pages":"Pages 40-47"},"PeriodicalIF":3.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733614","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

Glutathionylation and metabolic dysfunction-associated steatotic liver disease 谷胱甘肽化与代谢功能障碍相关的脂肪变性肝病。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-03-25 DOI: 10.1016/j.biochi.2025.03.006

Zhe Jiang , Lin Chen , Xiaobing Dou

引用次数: 0