Chemico-Biological Interactions最新文献

{"title":"Binding characteristics of the major kratom alkaloid, mitragynine, towards serum albumin: Spectroscopic, calorimetric, microscopic, and computational investigations","authors":"Khairul Azreena Bakar ,&nbsp;Su Datt Lam ,&nbsp;Shevin Rizal Feroz","doi":"10.1016/j.cbi.2024.111264","DOIUrl":"10.1016/j.cbi.2024.111264","url":null,"abstract":"<div><div>Mitragynine (MTG) is a prominent indole alkaloid that is present abundantly in <em>Mitragyna speciosa</em>, commonly referred to as kratom. MTG has garnered significant attention due to its selective agonistic characteristics towards opioid receptors and related analgesic effects. In the circulatory system, the <em>in vivo</em> efficacy of MTG is dictated by its interaction with plasma proteins, primarily human serum albumin (HSA). In the present study, we utilized a broad methodology that included spectroscopic, calorimetric, microscopic, and <em>in silico</em> approaches to characterize the interaction between MTG and HSA. Alterations in the UV absorption spectrum of HSA by the presence of MTG demonstrated a ground-state complexation between the protein and the ligand. The <em>K</em>_a values obtained for the MTG–HSA interaction were in the range 10³–10⁴ M⁻¹ based on analysis of fluorescence and ITC data, respectively, indicating an intermediate binding affinity. The binding reaction was thermodynamically favorable as revealed by Δ<em>H</em>, Δ<em>S</em>, and Δ<em>G</em> values of −16.42 kJ mol⁻¹, 39.97 J mol⁻¹ K⁻¹, and −28.34 kJ mol⁻¹, respectively. Furthermore, CD spectroscopy results suggested MTG binding induced minimal effects on the structural integrity of HSA, supported by computational methods. Changes in the dimensions of HSA particles due to aggregation, as observed using atomic force microscopy in the presence of MTG. Competitive drug displacement results seemingly suggested site III of HSA located at subdomain IB as the preferred binding site of MTG, but were in inconclusive. However, docking results showed the clear preference of MTG to bind to site III, facilitated by hydrophobic (alkyl and pi-alkyl) and van der Waals forces, together with carbon hydrogen bonds. Additionally, the MTG–HSA complexation was demonstrated to be stable based on molecular dynamics analysis. The outcomes of this study shed light on the therapeutic potential of MTG and can help in the design of more effective derivatives of the compound.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"404 ","pages":"Article 111264"},"PeriodicalIF":4.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hinokiflavone from Platycladi cacumen as a potent broad-spectrum inhibitor of gut microbial Loop-1 β-glucuronidases: Inhibition kinetics and molecular simulation","authors":"Yue Han ,&nbsp;Yu-Tong Liu ,&nbsp;Lu Chen ,&nbsp;Hao-Fan Sun ,&nbsp;Guang-Hao Zhu ,&nbsp;Dong-Ning Kang ,&nbsp;Qi Zhou ,&nbsp;Hui Tang ,&nbsp;Yu-Ling Yin ,&nbsp;Jie Hou","doi":"10.1016/j.cbi.2024.111261","DOIUrl":"10.1016/j.cbi.2024.111261","url":null,"abstract":"<div><div>Gut microbial Loop-1 β-glucuronidases (gmGUS) played an important role in irinotecan-induced gastrointestinal toxicity by regulating the level of its active metabolite SN38 through enterohepatic recirculation. gmGUS inhibition has emerged as a promising approach to relieve its dose-limiting intestinal toxicity and improve its medication efficacy. This study aims to investigate the inhibitory effects and mechanisms of <em>Platycladi cacumen</em> and its main constituent hinokiflavone against four different types of Loop-1 gmGUS (<em>Ee</em>GUS, <em>Sa</em>GUS, <em>Cp</em>GUS and <em>Ec</em>GUS). Our results showed that the ethanol extract of <em>Platycladi cacumen</em> displayed strong broad-spectrum inhibition against four gmGUS, and hinokiflavone could potently inhibit <em>Ee</em>GUS, <em>Sa</em>GUS, <em>Cp</em>GUS and <em>Ec</em>GUS with IC₅₀ values of 0.09 ± 0.01 μM, 0.44 ± 0.01 μM, 0.20 ± 0.01 μM and 0.69 ± 0.10 μM, respectively. Inhibition kinetic analyses demonstrated that hinokiflavone acted as a strong competitive inhibitor of <em>Ee</em>GUS with <em>K</em>_<em>i</em> value of 0.13 μM, while it displayed non-competitive inhibition against <em>Sa</em>GUS, <em>Cp</em>GUS and <em>Ec</em>GUS, with the <em>K</em>_<em>i</em> values of 0.43 μM, 0.33 μM and 0.76 μM, respectively. Docking simulations revealed that hinokiflavone could tightly bind with Tyr-485 and Glu-516 in catalytic sites of <em>E</em>eGUS, as well it created strong interactions with amino acids in loop structures of <em>Sa</em>GUS (Asn-362), <em>Cp</em>GUS (Phe-363, Met-364, Ala-365 and Arg-375) and <em>Ec</em>GUS (Leu-361) to interfere the substrate entry into the catalytic pocket. Collectively, these results confirmed that hinokiflavone from <em>Platycladi cacumen</em> is a potent naturally occurring inhibitor of gmGUS with broad efficiency, suggesting hinokiflavone will be helpful for alleviating intestinal toxicity in irinotecan therapy.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"404 ","pages":"Article 111261"},"PeriodicalIF":4.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"4-Hydroxybenzoic acid restrains Nlrp3 inflammasome priming and activation via disrupting PU.1 DNA binding activity and direct antioxidation","authors":"Yanbo Kou ,&nbsp;Qiyue Jing ,&nbsp;Xiaoqing Yan ,&nbsp;Junru Chen ,&nbsp;Yusi Shen ,&nbsp;Yulu Ma ,&nbsp;Yaoyao Xiang ,&nbsp;Xiangyang Li ,&nbsp;Xiangye Liu ,&nbsp;Zhuanzhuan Liu ,&nbsp;Yanxia Wei ,&nbsp;Yugang Wang","doi":"10.1016/j.cbi.2024.111262","DOIUrl":"10.1016/j.cbi.2024.111262","url":null,"abstract":"<div><div>Reactive oxygen species (ROS) production is considered central to triggering the nucleotide-binding domain-like receptor family pyrin domain containing 3 (Nlrp3) inflammasome activation and the subsequent inflammatory responses. Coenzyme Q₁₀ (CoQ₁₀) plays a critical role in maintaining intracellular ROS homeostasis and inhibiting excessive Nlrp3 inflammasome activation. However, direct supplementation of CoQ₁₀ showed unsatisfactory clinical improvement due to its limited absorption and bioavailability. Therefore, stimulating endogenous CoQ₁₀ biosynthesis by supplementing CoQ₁₀ precursors may provide a more promising therapeutic approach. In this study, we described the role of 4-hydroxybenzoic acid (4-HBA), a precursor of CoQ₁₀, in attenuating excessive inflammatory responses. We found that while supplementation of 4-HBA inhibited the priming and activation of Nlrp3 inflammasome, this effect was independent of its metabolic transformation into CoQ₁₀. 4-HBA itself exhibits antioxidative activities. Furthermore, 4-HBA can disrupt the binding activity of PU.1 on the promoters of <em>Tlr4</em> and <em>Md2</em>, thereby directly suppressing Nlrp3 inflammasome priming during LPS-induced inflammatory responses. Therefore, strategically utilizing 4-HBA or increasing 4-HBA intake may represent a potential strategy for reducing excessive inflammation.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"404 ","pages":"Article 111262"},"PeriodicalIF":4.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the effects of pemetrexed on drug resistance mechanisms in human lung adenocarcinoma and its association with PGRMC1","authors":"Ssu-Yun Wu ,&nbsp;En-Chi Liao ,&nbsp;Yueh-Feng Wen ,&nbsp;Yi-Shiuan Wang ,&nbsp;Han Meng ,&nbsp;Hsiu-Chuan Chou ,&nbsp;Hong-Lin Chan","doi":"10.1016/j.cbi.2024.111259","DOIUrl":"10.1016/j.cbi.2024.111259","url":null,"abstract":"<div><div>According to the 2022 cancer statistics of the World Health Organization, lung cancer ranks among the top ten causes of death, with lung adenocarcinoma being the most prevalent type. Despite significant advancements in lung cancer therapeutics, many clinical limitations remain, primarily due to the development of drug resistance. The present study investigated the effects of pemetrexed on the drug resistance mechanisms in human lung adenocarcinoma and its association with progesterone receptor membrane component 1 (PGRMC1) expression. Given that KRAS-mutant lung adenocarcinoma cell lines (e.g., A549) exhibit a high folate synthesis activity, pemetrexed, which is structurally similar to folate, was selected as the therapeutic drug. The present study used a lung adenocarcinoma cell line (A549) and established a drug-resistant lung adenocarcinoma cell line (A549/PEM). The findings demonstrated that PGRMC1 expression was elevated in the A549/PEM cells. It has been hypothesized that PGRMC1 regulates iron absorption through heme binding, resulting in a preference for iron-related cell death pathways (ferroptosis). Our findings indicate that drug-resistant lung adenocarcinoma cells with high PGRMC1 levels exhibit elevated antioxidant activity on the cell membrane and increased reliance on iron-dependent cell death pathways. This suggests a correlation between PGRMC1 and pemetrexed-induced iron-dependent cell death. Our study contributes to the development of more effective therapeutic strategies to improve the prognosis of patients with lung adenocarcinoma, particularly those facing drug resistance challenges.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"403 ","pages":"Article 111259"},"PeriodicalIF":4.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homocysteine decreases VEGF, EGF, and TrkB levels and increases CCL5/RANTES in the hippocampus: Neuroprotective effects of rivastigmine and ibuprofen","authors":"Osmar Vieira Ramires Júnior ,&nbsp;Josiane Silva Silveira ,&nbsp;Darlan Gusso ,&nbsp;Gustavo Ricardo Krupp Prauchner ,&nbsp;Bruna Ferrary Deniz ,&nbsp;Wellington de Almeida ,&nbsp;Lenir Orlandi Pereira ,&nbsp;Angela TS. Wyse","doi":"10.1016/j.cbi.2024.111260","DOIUrl":"10.1016/j.cbi.2024.111260","url":null,"abstract":"<div><div>Homocysteine (Hcy) is produced through methionine transmethylation. Elevated Hcy levels are termed Hyperhomocysteinemia (HHcy) and represent a risk factor for neurodegenerative conditions such as Alzheimer's disease. This study aimed to explore the impact of mild HHcy and the neuroprotective effects of ibuprofen and rivastigmine via immunohistochemical analysis of glial markers (Iba-1 and GFAP). Additionally, we assessed levels of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), chemokine ligand 5 (CCL5/RANTES), CX3C chemokine ligand 1 (CX3CL1), and the NGF/p75NTR/tropomyosin kinase B (TrkB) pathway in the hippocampus of adult rats. Mild chronic HHcy was induced chemically in Wistar rats by subcutaneous administration of Hcy (4 mg/kg body weight) twice daily for 30 days. Rivastigmine (0.5 mg/kg) and ibuprofen (40 mg/kg) were administered intraperitoneally once daily. Results revealed elevated levels of CCL5/RANTES and reduced levels of VEGF, EGF, and TrkB in the hippocampus of HHcy-exposed rats. Rivastigmine mitigated the neurotoxic effects of HHcy by increasing TrkB and VEGF levels. Conversely, ibuprofen attenuated CCL5/RANTES levels against the neurotoxicity of HHcy, significantly reducing this chemokine's levels. HHcy-induced neurochemical impairment in the hippocampus may jeopardize neurogenesis, synapse formation, axonal transport, and inflammatory balance, leading to neurodegeneration. Treatments with rivastigmine and ibuprofen alleviated some of these detrimental effects. Reversing HHcy-induced damage through these compounds could serve as a potential neuroprotective strategy against brain damage.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"403 ","pages":"Article 111260"},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silicon dioxide particles induce DNA oxidative damage activating the AIM2-mediated PANoptosis in mice cerebellum","authors":"Hao Cai ,&nbsp;Meichen Gao ,&nbsp;Tong Xu ,&nbsp;Ke Li ,&nbsp;Yuanxin Zhou ,&nbsp;Chencong Lyu ,&nbsp;Shiwen Xu","doi":"10.1016/j.cbi.2024.111258","DOIUrl":"10.1016/j.cbi.2024.111258","url":null,"abstract":"<div><div>Silicon dioxide (SiO₂) particles are novel materials with wide-ranging applications across various fields, posing potential neurotoxic effects. This study investigates the toxicological mechanisms of SiO₂ particles of different sizes on murine cerebellar tissue and cells. Six-week-old C57BL/6 mice were orally administered SiO₂ particles of three sizes (1 μm, 300 nm, 50 nm) for 21 days to establish an in vivo model, and mice cerebellar astrocytes (C8-D1A cells) were cultured in vitro. Indicators of oxidative stress, DNA damage, and the PANoptosis pathway were detected using methods such as immunofluorescence staining, comet assay, western blotting, and qRT-PCR. The results show that SiO₂ particles induce oxidative stress leading to DNA oxidative damage. The aberrant DNA is recognized by AIM2 (absent in melanoma 2), which activates the assembly of the PANoptosome complex, subsequently triggering PANoptosis. Furthermore, the extent of damage is inversely correlated with the size of SiO₂ particles. This study elucidates the toxicological mechanism of SiO₂ particles causing cerebellar damage via PANoptosis, extending research on PANoptosis in neurotoxicology, and aiding in the formulation of stricter safety standards and protective measures to reduce the potential toxic risk of SiO₂ particles to humans.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"403 ","pages":"Article 111258"},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PP2 suppresses proliferation and migration of C6 Glioma and MDA-MB-231 cells by targeting both fibroblast growth factor receptor 1 and Src","authors":"Yanyan Yang ,&nbsp;Ningning Tang ,&nbsp;Yan Liu ,&nbsp;Wooram Choi ,&nbsp;Ji Hye Kim ,&nbsp;Han Gyung Kim ,&nbsp;Tao Yu ,&nbsp;Jae Youl Cho","doi":"10.1016/j.cbi.2024.111252","DOIUrl":"10.1016/j.cbi.2024.111252","url":null,"abstract":"<div><div>Fibroblast growth factor (FGF) is involved in the progression of glioma, a most common type of brain tumor, and breast tumors. In this study, we aim to evaluate the effects of the inhibitor PP2 on cell proliferation and migration in glioma and breast tumor cells, and to characterize the molecular mechanisms involved in these processes. The inhibitory effect of PP2 on the tumorigenic potential of C6 glioma and MDA-MB-231 cells was examined by proliferation, migration, and invasion assays, and apoptotic analysis. The molecular mechanism behind the anti-glioma activity of PP2 was investigated by immunoblotting, immunoprecipitation, phosphoprotein assay, cellular thermal shift assay (CETSA), and molecular docking modeling. PP2 suppressed the proliferation and migration of C6 glioma and MDA-MB-231 cells via FGF2. Moreover, PP2 directly blocked the enzyme activity of FGF receptor 1 (FGFR1) and Src, subsequently affecting the nuclear factor-κB and activator protein-1 signaling pathways. CETSA analysis and the docking model indicated that the TK1 domains (Val 492 ad Glu 486) of FGFR2 could be binding sites of PP2. Collectively, therefore, our findings suggest that PP2 mediates antitumor effects by targeting both FGFR1 and Src and may have applications as a therapeutic inhibitor for the treatment of glioma.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"403 ","pages":"Article 111252"},"PeriodicalIF":4.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142326776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocytic pathways and metabolic fate of colloidal bismuth subcitrate in human renal cells","authors":"Yang Yang ,&nbsp;Mengfei Tan ,&nbsp;Jinbin Cui,&nbsp;He Liu,&nbsp;Hezhang Meng,&nbsp;Xiaju Cheng,&nbsp;Yangyun Wang,&nbsp;Yong Wang,&nbsp;Leshuai W. Zhang","doi":"10.1016/j.cbi.2024.111256","DOIUrl":"10.1016/j.cbi.2024.111256","url":null,"abstract":"<div><div>Bismuth compounds, particularly colloidal bismuth subcitrate (CBS), have been widely used in the treatment of gastrointestinal diseases. However, overdose of CBS has been linked to cases of acute renal failure, primarily due to the intracellular accumulation of bismuth in the kidney. To date, the detailed mechanisms of CBS internalization and its metabolic fate remain unclear. In this study, CBS was characterized as a type of nano-object using transmission electron microscopy and dynamic light scattering. Renal cells internalized CBS primarily via clathrin-mediated endocytosis in an active transport manner. Gene knockdown techniques revealed that CBS binds to the transferrin receptor likely through complexing with transferrin before cellular uptake. Once internalized, CBS was sorted into early endosomes, late endosomes, and lysosomes, mediated by microtubules and the Golgi apparatus. Additionally, differentially expressed genes analysis revealed that CBS endocytosis stimulated oxidative stress, significantly affecting the metabolism of glutathione and cysteine within cells. This led to the formation of black bismuth sulfide particles as a result of CBS conjugating with intracellular glutathione. These findings provide crucial insights into the cellular mechanisms underlying excessive CBS exposure, which is essential for understanding and potentially mitigating the risks associated with the use of bismuth compounds in medical treatments.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"403 ","pages":"Article 111256"},"PeriodicalIF":4.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142326766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lanostane triterpenoids from Ganoderma calidophilum exhibit potent anti-tumor activity by inhibiting PTP1B","authors":"Chuan Chen ,&nbsp;Ruixuan Xu ,&nbsp;Chenxiao Guo ,&nbsp;Xiangke Li ,&nbsp;Youxing Zhao ,&nbsp;Duqiang Luo","doi":"10.1016/j.cbi.2024.111253","DOIUrl":"10.1016/j.cbi.2024.111253","url":null,"abstract":"<div><div>The species <em>Ganoderma calidophilum</em> represents a distinct variety within the genus Ganoderma and used by the indigenous Li ethnic group as a medicinal agent for the prevention and treatment of cancer. However, the precise biological activity and role of <em>G. calidophilum</em> in antitumor treatment remain largely unresolved. Several lanostane triterpenoids have been isolated from <em>G</em>. <em>calidophilum</em>. The enzyme activity analysis revealed that four lanostane triterpenoids exhibited PTP1B inhibition activity, with minimal inhibition towards SHP2, SHP1, PTPN5, PTPRA, STEP and TCPTP. Molecular docking analysis demonstrated that these compounds primarily bind to the substrate recognition and entry regions of PTP1B. Further analysis indicated that among them, ganoderic aldehyde A (GAA) is a selective and non-competitive PTP1B inhibitor. GAA inhibited the proliferation, colony formation and migration of C33A and MDA-MB-231 cells in a dose-dependent manner. GAA has the capacity to induce apoptosis in a cell-type-specific manner, both in a caspase-dependent and -independent manner. PTP1B siRNA significantly reduced the cytotoxic effect of GAA, while overexpression of PTP1B significantly increased cell growth after GAA treatment. These findings confirm that PTP1B is a functional target of GAA. Research into the mechanisms of action of GAA has revealed that it could inhibit the activation of AKT by inhibiting PTP1B, while simultaneously activating p38, which promotes cell death. It is possible to develop specific PTP1B inhibitors based on the lanosterol triterpene skeleton. <em>G. calidophilum</em> has the potential to be developed into functional foods or drugs with the aim of preventing and treating cancer.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"403 ","pages":"Article 111253"},"PeriodicalIF":4.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of the interaction mechanism of γ-globulin and hemoglobin with spherical and rod-shaped gold nanoparticles","authors":"Xiangrong Li ,&nbsp;Xinzhe Wu ,&nbsp;Yujie Sun ,&nbsp;Zhizhi Song ,&nbsp;Li Shi ,&nbsp;Ze Dong","doi":"10.1016/j.cbi.2024.111257","DOIUrl":"10.1016/j.cbi.2024.111257","url":null,"abstract":"<div><div>The interaction mechanism of spherical gold nanoparticles (AuNPs) and rod-shaped gold nanoparticles (AuNRs) with γ-globulin and hemoglobin was comprehensively and comparatively analyzed. γ-Globulin and hemoglobin have high affinity with AuNPs, and with two different types of binding sites on AuNRs surface. Except hemoglobin interaction with the first binding site of AuNRs, the interaction between γ-globulin/hemoglobin and AuNPs/AuNRs is the spontaneous, endothermic and entropy-driven process, and hydrophobic interaction plays a dominant role. The molecular adsorption mechanism of γ-globulin/hemoglobin on AuNPs and AuNRs surface conforms to Langmuir model and Freundlich model, respectively. The kinetic molecular mechanism between them conforms to the pseudo-second-order model, and chemisorption is the rate-limiting step. AuNPs result in the loosening and unfolding of γ-globulin backbone. AuNRs have no significant effect on γ-globulin backbone. AuNPs/AuNRs result in no significant changes in hemoglobin structure and heme group microenvironment. AuNPs/AuNRs decrease the hydrophobicity of Trp microenvironment of γ-globulin, but there is an intramolecular energy transfer from Trp residue to Tyr residue of hemoglobin. The β-sheet of γ-globulin and the α-helix of hemoglobin reduce by increasing concentrations of AuNPs/AuNRs. Molecular docking is suggesting that the specific amino acid residues of γ-globulin and hemoglobin interaction with AuNPs/AuNRs, and validates the experimental results.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"403 ","pages":"Article 111257"},"PeriodicalIF":4.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}