Biochimie最新文献

{"title":"50 years since the concept of homeoviscous adaptation","authors":"Dmitry A. Los,&nbsp;Anna V. Leusenko","doi":"10.1016/j.biochi.2024.12.008","DOIUrl":"10.1016/j.biochi.2024.12.008","url":null,"abstract":"<div><div>This mini review focuses on the phenomenon of homeoviscous adaptation (HVA). The concept, which dominated for decades, had a significant impact on membrane and lipid research. It includes the functional characterization of biological membranes and their domains, the role of lipids and fatty acids in cell metabolic control, and the characterization of fatty acid desaturases and their roles in membrane properties modulation. This hypothesis led to the discovery of a feed-back manner of desaturase expression and membrane-associated temperature sensors in bacteria.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"231 ","pages":"Pages 98-103"},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873759","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":"Distinctive aspects of ligand binding to G4 DNA structure flanked by the double helix","authors":"Liana L. Tevonyan,&nbsp;Timerkhan M. Fatkullin,&nbsp;Artemy D. Beniaminov,&nbsp;Dmitry N. Kaluzhny","doi":"10.1016/j.biochi.2024.12.005","DOIUrl":"10.1016/j.biochi.2024.12.005","url":null,"abstract":"<div><div>Except for telomeres, G4 DNA structures in the human genome can be formed only within the context of double-stranded DNA. DNA duplexes flanking the G4 structure may potentially affect the G4 architecture and the binding of G4-specific ligands. Here, we examine the interaction of TMPyP4, NMM, and PDS ligands with three structures formed by the same DNA fragment containing the (GGGT)₄ sequence: the G4 in duplex (dsG4), G4 in single-stranded DNA (ssG4) and perfect duplex DNA (ds). To design a structure-specific fluorescent sensor, single thymine loops or proximal positions in DNA duplex were modified with FAM. Ligand-induced fluorescence quenching revealed a preferential binding of TMPyP4 and NMM with the dsG4 and ssG4 structures over the flanking duplex part or double-stranded DNA. PDS could not quench the fluorophores attached to single-nucleotide loops of the G4 DNA, although gel mobility assay confirmed tight binding of the ligand to the ssG4 or dsG4 structures. We hypothesize that the selectivity of the ligands for G4 loops compared to duplexes is responsible for the high quenching efficiency. Distinctive features of ligand interactions with G4 DNA in a duplex context suggest the potential for developing specific ligands for the genomic G4 structure.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"230 ","pages":"Pages 166-171"},"PeriodicalIF":3.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824908","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":"Achatina fulica haemocyanin-derived peptides as novel antimicrobial agents","authors":"Andrés Esteban Pereira ,&nbsp;Libardo Suarez ,&nbsp;Tanya Roman ,&nbsp;Fanny Guzmán ,&nbsp;Leidy Sierra ,&nbsp;Bladimiro Rincón-Orozco ,&nbsp;William Hidalgo","doi":"10.1016/j.biochi.2024.12.007","DOIUrl":"10.1016/j.biochi.2024.12.007","url":null,"abstract":"<div><div>Haemocyanin-derived peptides were previously found in semi-purified fractions of mucus secretion from the snail <em>Achatina fulica</em>, which exhibited an inhibitory effect on <em>Staphylococcus aureus</em> strains. Here, an <em>in silico</em> rational design strategy was employed to generate new antimicrobial peptides (AMPs) from <em>A. fulica</em> haemocyanin-derived peptides (AfH). The designed peptides were chemically synthetized using the Fmoc strategy, and their antimicrobial activity against <em>Escherichia coli</em> and <em>S. aureus</em> strains was evaluated using the broth microdilution method. In addition, the cytotoxic activity on Vero, HaCat, and human erythrocyte cells was also determined. The results demonstrated that 15-residue alpha-helical and cationic synthetic peptides exhibited the highest biological activity against Gram-positive strains, with minimum inhibitory concentrations (MIC) in the range from 7.5 to 30 μM. The positive selectivity index suggests a higher selectivity, primarily on the microorganisms evaluated, but not on eukaryotic cells. In this study, <em>A. fulica</em> hemocyanin was identified as an appropriate protein model for the rational design of AMPs against bacteria of public health significance. Further studies are required to evaluate the activity of the peptides on Gram-negative bacteria other than <em>E. coli</em>.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"231 ","pages":"Pages 84-97"},"PeriodicalIF":3.3,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840604","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":"Helicid: A novel Anti-Staphylococcus aureus adjuvant","authors":"Yufen Li ,&nbsp;Haofang Zhou ,&nbsp;Teri Gele ,&nbsp;Chunjie Hu ,&nbsp;Chang Liu ,&nbsp;Wu Song ,&nbsp;Lin Wei ,&nbsp;Danning Song ,&nbsp;Mengli Jin ,&nbsp;Yating Tang ,&nbsp;Qingjie Li ,&nbsp;Shuang Jiang ,&nbsp;Gang Yuan ,&nbsp;Xin Su","doi":"10.1016/j.biochi.2024.12.002","DOIUrl":"10.1016/j.biochi.2024.12.002","url":null,"abstract":"<div><div>Staphylocoagulase (Coa) plays a critical role in the pathogenicity of <em>Staphylococcus aureus</em> (<em>S. aureus</em>). The present study was undertaken to investigate the underlying mechanism which helicid (HEL) suppressed the virulence factor Coa, as well as to assess the synergistic inhibitory effects of HEL in conjunction with antibiotics, thereby establishing the potential of HEL as an antibacterial adjuvant. We employed coagulation and biofilm assays to comprehensively assess the inhibitory impact of HEL on <em>S. aureus</em> pathogenicity. The thermal shift assay demonstrated that HEL exerted a direct impact on the protein stability of Coa, evidenced by a 6 °C change in melting temperature (Δ<em>Tm</em>) at a concentration of 100 μM. HEL binding to Coa proteins was further validated by molecular dynamics simulations and fluorescence quenching. Molecular docking and point mutation assays identified S23 and D112 as crucial binding sites for HEL and Coa. Furthermore, HEL has been observed to potentiate the bactericidal properties of ceftaroline fosamil (CEF-F), concurrently diminishing the resistance exhibited by <em>S. aureus</em> towards CEF-F, as demonstrated by antibiotic synergy tests and resistance induction assays. The combination of HEL and CEF-F effectively reduced the number of bacteria and improved the survival of both <em>Galleria mellonella</em> larvae and mice. Additionally, a significant decrease was observed in the levels of TNF-α, IL-6, and IFN-γ in mice broncho-alveolar lavage fluid (BALF). Ultimately, our findings confirmed that the direct binding of HEL to Coa could diminish the pathogenicity of <em>S. aureus</em>. Moreover, the combination with CEF-F substantially reduced the lethality associated with <em>S. aureus</em>-infected pneumonia and extended the efficacy of the antibiotic.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"231 ","pages":"Pages 46-60"},"PeriodicalIF":3.3,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840605","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":"Combination of chemotherapy and c-MET inhibitors has synergistic effects in c-MET overexpressing pancreatic cancer cells","authors":"Fatemeh Moosavi ,&nbsp;Roya Firoozi ,&nbsp;Marjan Tavakkoli ,&nbsp;Somayeh Nazari ,&nbsp;Alireza Alipour ,&nbsp;Omidreza Firuzi","doi":"10.1016/j.biochi.2024.12.006","DOIUrl":"10.1016/j.biochi.2024.12.006","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) remains as one of the most lethal malignancies. c-MET is an important oncogenic kinase involved in PDAC progression. We determined the anticancer effect of c-MET inhibitors, crizotinib and cabozantinib, combined with chemotherapeutic agents, doxorubicin, oxaliplatin and gemcitabine, against different PDAC and a lung adenocarcinoma cell line expressing different levels of c-MET. MTT assay was performed to assess cell growth inhibition. Synergistic combinations were evaluated in spheroid cultures, while apoptosis was determined through Hoechst33258 staining. The effect of drug combinations on cell cycle and apoptosis induction was examined by RNase/PI flow cytometric assay. We also evaluated reactive oxygen species (ROS) levels using 2′,7′-dichlorofluorescein-diacetate (DCFH-DA) assay to explore the possible mechanisms contributing to synergism. Combination of crizotinib or cabozantinib with doxorubicin exhibited synergistic effects in c-MET overexpressing cells. Conversely, combinations of c-MET inhibitors with other agents were additive or even antagonistic. Combination index (CI) values calculated with Calcusyn software were 0.631–0.730 for crizotinib and 0.542–0.746 for cabozantinib co-administered with doxorubicin. These synergistic combinations showed significant spheroid growth inhibition and apoptosis induction in Suit-2, c-MET dependent PDAC cells. These combinations also significantly increased the number of cells in both apoptotic sub-G1 phase and the G2/M phase compared to single-drug treatment. Increased ROS production seemed to be a possible mechanism underlying synergism. In conclusion, c-MET inhibitors synergize with DNA damaging agent, doxorubicin, in cancer cells with c-MET overexpression, indicating that these combination therapies may be a promising cancer therapeutic strategy.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"231 ","pages":"Pages 73-83"},"PeriodicalIF":3.3,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831180","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":"Optimized high-yield expression of envelope glycoprotein domain III from dengue virus serotypes 1 to 4","authors":"Disharee Mallick ,&nbsp;Vanshika Tyagi ,&nbsp;Anjali Saroj ,&nbsp;Mandar Bhutkar ,&nbsp;Vivek Kumar ,&nbsp;Manjima Das ,&nbsp;Rishav Madhukalya ,&nbsp;Shweta Choudhary ,&nbsp;Rohit Gupta ,&nbsp;Vishakha Singh ,&nbsp;Dilip Kumar ,&nbsp;Shailly Tomar ,&nbsp;Rajesh Kumar","doi":"10.1016/j.biochi.2024.12.003","DOIUrl":"10.1016/j.biochi.2024.12.003","url":null,"abstract":"<div><div>Dengue virus (DENV) envelope glycoprotein Domain III (EDIII) is critical for viral entry, highly immunogenic, and induces robust neutralizing antibody response. It is a prominent candidate for designing subunit-based vaccines and can also be harnessed as an antigenic bait for isolation of neutralizing human mAbs. Here, we describe an optimized method for high-yield expression of recombinant domain EDIII protein from DENV serotypes 1 to 4 in different <em>Escherichia coli (E. coli)</em> expression strains. The DENV EDIII proteins show differential expression patterns in tested <em>E. coli</em> expression strains. The structural integrity of the purified and refolded proteins is further validated using the Circular Dichroism (CD) spectroscopy and Fourier Transform Infrared (FTIR) spectroscopic analysis. The functional validation of the purified refolded DENV EDIII proteins through Enzyme-linked Immunosorbent Assay (ELISA) and co-immunoprecipitation (Co-IP) exhibits efficient binding with a well-characterized humanized neutralizing mAb 513. Further, we compared the potency of purified EDIII in blocking viral through competitive inhibition assay. Our study highlights that a universal expression system may not be an ideal approach for all DENV EDIII protein expression.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"231 ","pages":"Pages 61-72"},"PeriodicalIF":3.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822989","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":"Convergence of plant sterols and host eukaryotic cell-derived defensive lipids at the infectious pathogen-host interface","authors":"Darab Ghadimi ,&nbsp;Regina Fölster-Holst ,&nbsp;Sophia Blömer ,&nbsp;Michael Ebsen ,&nbsp;Christoph Röcken ,&nbsp;Jumpei Uchiyama ,&nbsp;Shigenobu Matsuzaki ,&nbsp;Wilhelm Bockelmann","doi":"10.1016/j.biochi.2024.12.001","DOIUrl":"10.1016/j.biochi.2024.12.001","url":null,"abstract":"<div><div>Plant sterols (PSs) exhibit intrinsic functions such as antibacterial effects. Their effects simultaneously on both host-mediated and bacteria-mediated pathogenesis are not yet fully understood. We hypothesized that when absorptive cells, defensive cells and detoxer cells are cultured together, their convergent response to an infectious pathogen depends on the molecular mimicry between the ingested sterols and their own defensive lipids. A human triple cell co-culture model incorporating colonocytes, macrophages, and hepatocytes was established. Cocultures were stimulated with <em>Klebsiella pneumoniae</em> 52145 (Kp52145) in the presence of pure plant sterol (β-sitosterol, PS) for 6 h. Changes in the structural health markers of the stimulated cocultured cells and their immune response and biochemical markers of pathogenicity were determined. PS significantly inhibited the secretion of cytokines induced by Kp52145. Cell viability was higher in the Kp52145 + PS group compared to the Kp52145 alone group. PS decreased Kp52145-induced marker of pathogenicity (SOD), accompanied by reduced levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), mannose binding lectin (MBL), and pentraxin 3 (PTX3) which are the mediators and enzymes associated with the inflammatory response to an infectious-inflamed milieu. PS recovered Kp52145-decreased peroxidase (POX), catalase (CAT), complement component 3 (C3), and high-density lipoprotein cholesterol (HDL-C) values. Convergence of ingested plant sterols and host eukaryotic cell-derived defensive lipids mitigates the disruptive effects of bacterial toxic effector molecules. Structural or immunological similarities (molecular mimicry) between ingested plant sterols and host defensive lipids play an important role in modulating bacterial signalling that occurs at the pathogen-host interface and in the mitigation of infection- and inflammation-driven pathological processes.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"231 ","pages":"Pages 35-45"},"PeriodicalIF":3.3,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796522","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}

{"title":"Metabolomic characterization of a new strain of microalgae by GC-MS method with the introduction of a deuterium label","authors":"Anna Vishnevskaya ,&nbsp;Anton Bashilov ,&nbsp;Sergey Osipenko ,&nbsp;Albert Kireev ,&nbsp;Maria Sinetova ,&nbsp;Eugene Nikolaev ,&nbsp;Yury Kostyukevich","doi":"10.1016/j.biochi.2024.11.015","DOIUrl":"10.1016/j.biochi.2024.11.015","url":null,"abstract":"<div><div>Microalgae are active producers of various compounds, including toxic substances. However, their metabolism is very diverse and insufficiently known. We demonstrate an approach that includes growing a new strain of cyanobacterium <em>Leptolyngbya</em> sp. (IPPAS B-1204) on an isotopically labeled medium (D₂O) and evaluating the metabolomic composition of these microorganisms after deuterium uptake. Despite the low resolution of the GC-MS method, the interpretation of the obtained spectra allowed us to find out not only the amount of the embedded isotope label but also to assume the position in the structure where the label is embedded. We present the results of reliably detecting more than 30 compounds with isotope labels belonging to various classes of biological compounds produced by this cyanobacterium, revealing the metabolic pathways of entry of this label. We also demonstrate that the synthesis of unsaturated fatty acids is suppressed under the growth on D₂O medium. In addition, we found an isotopic effect in the chromatographic separation of isotopically labeled compounds in gas chromatography. These data can be used in the future both for the identification of compounds and the analysis of the biosynthesis pathways of secondary biologically active compounds and in the analysis of the production of isotopically labeled standards of compounds.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"231 ","pages":"Pages 23-34"},"PeriodicalIF":3.3,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792994","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":"Macromolecules from mushrooms, venoms, microorganisms, and plants for diabetes treatment - Progress or setback?","authors":"Asmaa Chbel ,&nbsp;Ayoub Lafnoune ,&nbsp;Imane Nait Irahal ,&nbsp;Noureddine Bourhim","doi":"10.1016/j.biochi.2024.07.004","DOIUrl":"10.1016/j.biochi.2024.07.004","url":null,"abstract":"<div><div>Diabetes is a substantial public health issue, while its prevalence continues to rise worldwide, affecting millions of persons between the ages of 20 and 80, the development of new therapeutic classes improving glycemic control and consequently micro and macrovascular complications are needed. Today, diabetes treatment is daily for life, and should not be interrupted. However, insulin secretagogues medications, and exogenous self-administration of insulin provide efficient antidiabetic effects, but their misuse leads to hypoglycemic complications besides other risks, hence the need to look for other natural products not to use solely but in concert with others types of medications. In this review, we will highlight briefly the pathophysiology of diabetes and its complications, then we will report the main bioactive macromolecules derived from various sources of natural products providing anti-diabetic properties. However, further researches need to be carried out to face the limitations hampering the development of effective natural drugs for diabetes treatment.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 119-128"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141602371","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":"Assessment of membrane labelling mechanisms with exogenous fatty acids and detergents in bacteria","authors":"Laila Zaatouf ,&nbsp;Kiran Kumar ,&nbsp;Isabelle Marcotte ,&nbsp;Dror E. Warschawski","doi":"10.1016/j.biochi.2024.05.024","DOIUrl":"10.1016/j.biochi.2024.05.024","url":null,"abstract":"<div><div>Labelling of bacterial membranes using exogenous fatty acids has proven to be a valuable tool to investigate molecular interactions by in-cell solid-state nuclear magnetic resonance (ssNMR) spectroscopy, notably with antimicrobial peptides. However, the mechanism by which this labelling takes place in non-mutated bacteria has not yet been investigated. In this work, we propose a rapid method to assess the fate of the fatty acids during the labelling of bacteria, involving two different methylation schemes and gas chromatography coupled to mass spectrometry. We applied this approach to Gram(+) and Gram(−) bacteria grown with deuterated palmitic acid under different conditions. We assessed the extent of labelling, then the resulting membrane rigidity by ²H ssNMR. Our results reveal that the labelling mechanism depends on the detergent used to micellize the fatty acids. This labelling can be either <em>active</em> or <em>passive</em>, whether the fatty acids are metabolized and used in the phospholipids biosynthesis, or remain unmodified in the membrane. We discuss the best labelling protocol for studying peptide-membrane interactions.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 12-18"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201583","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}