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}
BiochimiePub Date : 2025-02-01DOI: 10.1016/j.biochi.2024.10.007
Michaela Dobrovolná , Jean-Louis Mergny , Václav Brázda
{"title":"Complete analysis of G-quadruplex forming sequences in the gapless assembly of human chromosome Y","authors":"Michaela Dobrovolná , Jean-Louis Mergny , Václav Brázda","doi":"10.1016/j.biochi.2024.10.007","DOIUrl":"10.1016/j.biochi.2024.10.007","url":null,"abstract":"<div><div>Recent advancements have finally delivered a complete human genome assembly, including the elusive Y chromosome. This accomplishment closes a significant knowledge gap. Prior efforts were hampered by challenges in sequencing repetitive DNA structures such as direct and inverted repeats. We used the G4Hunter algorithm to analyze the presence of G-quadruplex forming sequences (G4s) within the current human reference genome (GRCh38) and the new telomere-to-telomere (T2T) Y chromosome assemblies. This analysis served a dual purpose: identifying the location of potential G4s within the genomes and exploring their association with functionally annotated sequences. Compared to GRCh38, the T2T assembly exhibited a significantly higher prevalence of G-quadruplex forming sequences. Notably, these repeats were abundantly located around precursor RNA, exons, genes, and within protein binding sites. This remarkable co-occurrence of G4-forming sequences with these critical regulatory regions suggests their role in fundamental DNA regulation processes. Our findings indicate that the current human reference genome significantly underestimated the number of G4s, potentially overlooking their functional importance.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 49-57"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402319","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.2024.10.012
Mohammed K. Hankir , Christelle Le Foll
{"title":"Central nervous system pathways targeted by amylin in the regulation of food intake","authors":"Mohammed K. Hankir , Christelle Le Foll","doi":"10.1016/j.biochi.2024.10.012","DOIUrl":"10.1016/j.biochi.2024.10.012","url":null,"abstract":"<div><div>Amylin is a peptide hormone co-released with insulin from pancreatic β-cells during a meal and primarily serves to promote satiation. While the caudal hindbrain was originally implicated as a major site of action in this regard, it is becoming increasingly clear that amylin recruits numerous central nervous system pathways to exert multifaceted effects on food intake. In this Review, we discuss the evidence derived from preclinical studies showing that amylin and the related peptide salmon calcitonin (sCT) directly or indirectly target genetically distinct neurons in the caudal hindbrain (nucleus tractus solitarius and area postrema), rostral hindbrain (lateral parabrachial nucleus), midbrain (lateral dorsal tegmentum and ventral tegmental area) and hypothalamus (arcuate nucleus and parasubthalamic nucleus) via activation of amylin and/or calcitonin receptors. Given that the stable amylin analogue cagrilintide is under clinical development for the treatment of obesity, it is important to determine whether this drug recruits overlapping or distinct central nervous system pathways to that of amylin and sCT with implications for minimising any aversive effects it potentially causes. Such insight will also be important to understand how amylin and sCT analogues synergize with other molecules as part of dual or triple agonist therapies for obesity, especially the glucagon-like peptide 1 receptor (GLP-1R) agonist semaglutide, which has been shown to synergistically lower body weight with cagrilintide (CagriSema) in clinical trials.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 95-104"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiochimiePub Date : 2025-02-01DOI: 10.1016/j.biochi.2024.10.009
Ayşenur Güler , Berna Kavakcıoğlu Yardımcı , Nihal Şimşek Özek
{"title":"Human anti-apoptotic Bcl-2 and Bcl-xL proteins protect yeast cells from aging induced oxidative stress","authors":"Ayşenur Güler , Berna Kavakcıoğlu Yardımcı , Nihal Şimşek Özek","doi":"10.1016/j.biochi.2024.10.009","DOIUrl":"10.1016/j.biochi.2024.10.009","url":null,"abstract":"<div><div>Aging is a degenerative, biological, and time-dependent process that affects all organisms. Yeast aging is a physiological phenomenon characterized by the progressive transformation of yeast cells, resulting in modifications to their viability and vitality. Aging in yeast cells is comparable to that in higher organisms in some respects; however, due to their straightforward and well-characterized genetic makeup, these cells present unique advantages when it comes to researching the aging process. Here, we assessed the impact of human anti-apoptotic Bcl-2 and Bcl-xL proteins on aging using a yeast model. The findings clearly showed that these proteins exhibited remarkable anti-aging properties in yeast cells. Our data indicate that the presence of both proteins enhanced the reproductive survival of aging cells, likely by effecting the components functioning as both pro- and anti-oxidants, depending on the stage of yeast cell lifespan. Both proteins partially protected yeast cells from aging-related morphological deformations and cellular damage during the aging period. In particular, Bcl-xL expressing yeast cells reached the maximum activity levels for almost all of the major antioxidant enzymes and the total antioxidant status on the 8th day of lifespan and could provide effective protection at the latest stage of the investigated aging period. The chemometric data analysis of IR spectra confirmed the findings of the morphological and biochemical analyses. In this regard, specifically, understanding the mechanism of action on the cellular redox state of Bcl-xL in yeast may facilitate comprehension of its indirect antioxidant function in higher eukaryotes.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 69-83"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482920","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.2025.01.010
MA Adrianov , M Bobrov , I Mamedov , V Manskikh , EV Sheval , AA Rachkova , AM Shelechova , CM Eldarov , OA Averina , MY Vyssokikh
{"title":"A set of microRNAs are differentially expressed in cachexic naked mole rat colony members after chronic heavy burden under normoxia","authors":"MA Adrianov , M Bobrov , I Mamedov , V Manskikh , EV Sheval , AA Rachkova , AM Shelechova , CM Eldarov , OA Averina , MY Vyssokikh","doi":"10.1016/j.biochi.2025.01.010","DOIUrl":"10.1016/j.biochi.2025.01.010","url":null,"abstract":"<div><div>Enrichment of the habitat of captive rodents <em>Heterocephalus glaber</em> (naked mole rats) to implement their innate behavioral pattern of digging dense soil in search of food, paradoxically led to the appearance of unusual animals in the colony. They showed signs of cachexia, distinguished from other animals by a lower temperature (from 31 °C to 26 °C) and body mass index with decreasing proportion of subcutaneous fat. This animal demonstrated aggressive feeding behavior, but didn't gain weight even after finishing experiment with intensive physical activity. In histochemical analysis of tissues from cachexic and normal animals of the same age and sex liver hyperlipofuscinosis was revealed and indicated that animals when being in a habitat with an increased oxygen content for them (21 % versus 8 % in their natural underground habitat), experienced severe oxidative stress during physical exercise. Stress led to a disruption of the body's regulatory systems, a sharp increase in metabolism even at rest, an overload of the cardiovascular and respiratory systems and damage to organs and tissues. To clarify the pathogenetic mechanism of the observed phenomenon, microRNA was extracted from the animal tissues and sequenced. Then bioinformatics analysis of differential expression of microRNAs between groups of healthy animals and animals with idiopathic cachexia was performed.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"232 ","pages":"Pages 83-90"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082526","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}