Chemico-biological interactions最新文献

{"title":"Antifibrotic potential of reserpine (alkaloid) targeting Keap1/Nrf2; oxidative stress pathway in CCl₄-induced liver fibrosis.","authors":"Aamir Sohail, Faiza Shams, Aleeza Nawaz, Qurrat Ul Ain, Bushra Ijaz","doi":"10.1016/j.cbi.2025.111384","DOIUrl":"10.1016/j.cbi.2025.111384","url":null,"abstract":"<p><p>The death rate due to liver cancer approaches 2 million annually, the majority is attributed to fibrosis. Currently, there is no efficient, safe, non-toxic, and anti-fibrotic drug available, suggesting room for better drug discovery. The current study aims to evaluate the anti-fibrotic role of reserpine, an alkaloid plant compound against CCl₄-induced liver fibrosis. In-silico docking analysis showed the interaction of reserpine with keap1 protein with the binding energy -9.0 kcal/mol. In-vitro, biochemical analysis, anti-oxidative indexes, and inflammatory cytokines analysis were performed in HepG2 cells. The non-toxic nature of the compound (<100 μg/ml) was evaluated through MTT assay in HepG2 and Vero cell lines. The antifibrotic potential of the reserpine compound (dose of 0.5 mg/kg) was assessed in CCl₄-administered C57BL/6J mice models. Hematoxylin & Eosin and Masson staining were performed to study the morphological changes of liver tissues. Immune histochemistry (IHC) analysis was performed to evaluate the effect of reserpine on the liver fibrosis marker. The biochemical assay indicated a significant decrease in ALT, AST, and MDA levels and increased catalase enzyme post-6-week reserpine treatment in mice models. Gene expression analysis revealed that the reserpine targets oxidative stress Keap1/Nrf2 pathway and down-regulated Keap1 expression by 5-fold and up-regulated Nrf2 and Nqo1 expression by 6 and 4.5-fold respectively showing its antioxidant response. It suppressed the expression of Cyp2e1 by 2.2-fold, illustrating the compound's ability to block lipid peroxidation. Histological and immunostaining exhibited improved hepatocyte morphology and reduced collagen deposition in liver tissues due to reserpine. Reserpine treatment lowered the fibrotic markers α-SMA and Col-1 by 1.3 and 1.5 folds respectively as compared to the control group and increased the expression of miR-200a and miR-29b by 15.5 and 8.2 folds (p < 0.05) while decreased miR-128-1-5p expression by 5-fold. A comprehensive In-silico, In-vitro, and In-vivo analysis revealed that reserpine has a strong anti-fibrotic effect against the CCl₄-induced liver fibrosis in C57BL/6J mice model by targeting the Keap1/Nrf2 pathway.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111384"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prophylaxis by a reversible cholinesterase inhibitor and the NMDA receptor antagonist treatment as combinatorial countermeasure against nerve agent poisoning in mice model.","authors":"Jiri Kassa, Jan Konecny, Barbora Svobodova, Martin Horak, Jan Korabecny, Ondrej Soukup","doi":"10.1016/j.cbi.2025.111386","DOIUrl":"10.1016/j.cbi.2025.111386","url":null,"abstract":"<p><p>The current pharmacological pretreatment and medical treatment of nerve agent poisoning is an insufficiently addressed medical task. The prophylactic efficacy of a novel compound acting dually as an acetylcholinesterase inhibitor and NMDA receptor antagonist (K1959) and the therapeutic efficacy of a novel NMDA receptor antagonist (K2060) were evaluated in the NMRI mice model of nerve agent poisoning by tabun, soman and sarin. Their added value to the standard antidotal treatment (a combination of oxime reactivator and atropine) was also analyzed. The novel dually acting prophylactic drug (K1959) did not bring any additional benefit compared to the commonly used pyridostigmine. By contrast, an increase in the therapeutic efficacy of classic antidotal treatment was observed when the novel NMDA receptor antagonist (K2060) was combined with commonly used antidotes (oxime reactivator in combination with atropine). This novel combination reduced the acute toxicity of tabun, soman, and sarin more than two-fold, four-fold, and five-fold, respectively. These results highlight the possibility of NMDA antagonists such as K2060 as a supportive drug for the classic therapy of organophosphorus poisoning.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111386"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated network pharmacology, bioinformatics, and experiment analysis to decipher the molecular mechanism of Salidroside on Gastric cancer via targeting NCOA4-mediated ferritinophagy.","authors":"Yu Fu, Guiqin Huang, Yawen Cai, Menghui Ren, Run Cheng, Yuhui Chai, Yingdi Wang, Yunqi An, Tianhua Yan, Lingpeng Zhu, Xinxin Liu","doi":"10.1016/j.cbi.2024.111368","DOIUrl":"10.1016/j.cbi.2024.111368","url":null,"abstract":"<p><p>Gastric cancer (GC) is a highly aggressive and heterogeneous malignancy. The process of ferroptosis regulates tumor growth and represents a promising therapeutic target for GCs. Despite Salidroside (Sal) being able to regulate ferroptosis in a variety of diseases, there are still limited reports on its therapeutic effects and potential targets in treating GC. This study aimed to investigate the potential mechanism of Sal-induced ferroptosis in GC. Our analysis, integrating databases like PharmMapper, Swiss Target Prediction, TargetNet, GeneCards, TTD, OMIM, STRING, and DAVID. Human gastric cancer MGC803 cells and tumor-bearing mice were used to evaluate the anti-tumor effect of Sal on GC in vitro and in vivo. CCK-8, LDH, and Calcein-AM/PI were used to assess cell viability and damage. FerroOrange, Lillie's Ferrous Iron Stain, MDA, ROS, BODIPY™ 581/591C11, GSH, and GPxs were used to detect intracellular Fe²⁺ concentration, lipid peroxidation level, and antioxidant defense system. qRT-PCR and Western blot were performed to explore relevant mechanism studies. Network pharmacology results showed that Sal shares 322 targets with GC, which have biological functions related to lipid metabolism, cell death, and lipid peroxidation. Experiments further confirmed that Sal inhibits MGC803 cells by inducing ferroptosis, as evidenced by the induction of elevated Fe²⁺ and increased lipid peroxidation. Fer-1, an inhibitor of ferroptosis, reversed the anti-GC effect of Sal in MGC803 cells and GC tumor-bearing mice. Further confirmation of the association between Sal and ferroptosis in GC. Subsequently, bioinformatics and machine learning algorithms identified nuclear receptor coactivator 4 (NCOA4) as a candidate signature gene associated with ferroptosis in GC, and molecular docking shows that NCOA4 binds Sal. We then performed in vivo and in vitro experiments to elucidate that Sal targeting NCOA4, a cargo receptor mediating ferritinophagy, mediates autophagic degradation of ferritin heavy chain 1 (FTH1, Fe²⁺ storage protein), which further increases Fe²⁺ and lipid peroxidation. In addition, Sal induces mitochondrial dysfunction and increases mitochondrial ROS levels, which activates autophagy and triggers autophagic degradation of FTH1. Taken together, we revealed that NCOA4 is a new target for Sal-anchored GC and that Sal may be a potential therapeutic drug for the treatment of GC.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111368"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conformation and binding of 12 Microcystin (MC) congeners to PPP1 using molecular dynamics simulations: A potential approach in support of an improved MC risk assessment.","authors":"Sabrina Jaeger-Honz, Raymund Hackett, Regina Fotler, Daniel R Dietrich, Falk Schreiber","doi":"10.1016/j.cbi.2025.111372","DOIUrl":"10.1016/j.cbi.2025.111372","url":null,"abstract":"<p><p>Microcystins (MCs) occur frequently during cyanobacterial blooms worldwide, representing a group of currently about 300 known MC congeners, which are structurally highly similar. Human exposure to MCs via contaminated water, food or dietary supplements can lead to severe intoxications with ensuing high morbidity and in some cases mortality. Currently, one MC congener (MC-LR) is almost exclusively considered for risk assessment (RA) by the WHO. Many MC congeners co-occur during bloom events, of which MC-LR is not the most toxic. Indeed, MC congeners differ dramatically in their inherent toxicity, consequently raising question about the reliability of the WHO RA and the derived guidance values. Molecular dynamics (MD) simulation can aid in understanding differences in toxicity, as experimental validation for all known MC congeners is not feasible. Therefore, we present MD simulations of a total of twelve MC congeners, of which eight MC congeners were simulated for the first time. We show that depending on their structure and toxicity class, MCs adapt to different backbone conformations. These backbone conformations are specific to certain MC congeners and can change or shift to other conformations upon binding to PPP1, affecting the stability of the binding. Analysis of the interactions with PPP1 demonstrated that there are frequently occurring patterns for individual MC congeners, and that published PPP interactions could be reproduced. In addition, common but also unique patterns were found for individual MC congeners, suggesting differences in binding behaviour. The MD simulations presented here therefore enhance our understanding of MC congener-specific differences and demonstrated that congener-specific investigations are prerequisite for allowing characterisation of yet untested or even unknown MC congeners, thereby allowing for a novel potential approach in support of an improved RA of microcystins in humans.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111372"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel nano-sized N-Thiazolylpyridylamines targeting CDK2: Design, divergent synthesis, conformational studies, and multifaceted In silico analysis.","authors":"Samir Bondock, Nada Alabbad, Aisha Hossan, Ibrahim A Shaaban, Ali A Shati, Mohammad Y Alfaifi, SeragE I Elbehairi, Rehab H Abd El-Aleam, Moaz M Abdou","doi":"10.1016/j.cbi.2024.111366","DOIUrl":"10.1016/j.cbi.2024.111366","url":null,"abstract":"<p><p>This study involves the design, divergent synthesis, conformational and structural analysis, target prediction, and molecular docking simulations of novel nano N-thiazolylpyridylamines 2-7 and 10 as potential cyclin-dependent kinase 2 (CDK2) inhibitors. Using a divergent synthesis approach, the compounds were designed with structural variation and optimization in mind. The conformational and structural properties were explored through various spectroscopic techniques, confirming the structure, stability, and preferred conformations. Additionally, nanocrystalline characterization, including X-ray diffraction analysis, revealed the nanoscale structural features of the synthesized molecules. Most compounds exhibited a crystalline nature with crystallite sizes ranging from 10.75 to 57.77 nm, which is crucial for improving cellular uptake and anticancer efficacy. Biological testing was performed to evaluate the cytotoxicity of compounds 2-7 and 10 against cancer cell lines, including HepG2, MCF-7, and HCT-116. Compound 5 exhibited significant cytotoxicity with IC₅₀ values of 10.9 ± 0.5 μM, 6.98 ± 0.3 μM, and 6.3 ± 0.2 μM against MCF-7, HePG2, and HCT116, respectively. Other compounds demonstrated varied activities, with compounds 4, 6, and 10 showing moderate activity against the MCF-7 cell line. Computational techniques suggested a strong probability of these compounds targeting CDK2, with molecular docking and dynamics used to predict their binding mechanisms. These findings suggest that N-thiazolylpyridylamines may serve as new anticancer agents for further lead optimization.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":"407 ","pages":"111366"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel approach to the prevention and management of chemotherapy-induced cardiotoxicity: PANoptosis.","authors":"Chenchen Meng, Yali Wang, Tiantian Zheng, Zheng Rong, Zhengtian Lv, Chenxia Wu, Xinbin Zhou, Wei Mao","doi":"10.1016/j.cbi.2025.111379","DOIUrl":"10.1016/j.cbi.2025.111379","url":null,"abstract":"<p><p>As a fundamental component of antitumor therapy, chemotherapy-induced cardiotoxicity (CIC) has emerged as a leading cause of long-term mortality in patients with malignant tumors. Unfortunately, there are currently no effective therapeutic preventive or treatment strategies, and the underlying pathophysiological mechanisms of CIC remain inadequately understood. A growing number of studies have shown that different mechanisms of cell death, such as apoptosis, pyroptosis, and necroptosis, are essential for facilitating the cardiotoxic effects of chemotherapy. The PANoptosis mode represents a highly synchronized and dynamically balanced programmed cell death (PCD) process that integrates the principal molecular characteristics of necroptosis, apoptosis, and pyroptosis. Recent research has revealed a significant correlation between PANoptosis and the apoptosis of tumor cells. Chemotherapy drugs can activate PANoptosis, which is involved in the development of cardiovascular diseases. These findings suggest that PANoptosis marks the point where the effectiveness of chemotherapy against tumors overlaps with the onset and development of cardiovascular diseases. Furthermore, previous studies have demonstrated that CIC can simultaneously induce pyrodeath, apoptosis, and necrotic apoptosis. Therefore, PANoptosis may represent a potential mechanism and target for the prevention of CIC. This study explored the interactions among the three main mechanisms of PCD, pyroptosis, apoptosis, and necroptosis in CICs and analyzed the relevant literature on PANoptosis and CICs. The purpose of this work is to serve as a reference for future investigations on the role of PANoptosis in the development and mitigation of cardiotoxicity associated with chemotherapy.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111379"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alkaloids and nitrosamines in betel quid: A biochemical exploration of carcinogenicity.","authors":"S C Rangani, R A U J Marapana, G S A Senanayake, P R D Perera, M M Pathmalal, H K Amarasinghe","doi":"10.1016/j.cbi.2025.111383","DOIUrl":"10.1016/j.cbi.2025.111383","url":null,"abstract":"<p><p>Betel quid contains two major ingredients; Areca catechu and Piper betel, often consumed with slaked lime, tobacco, certain flavouring agents, colouring agents, herbs, and spices according to personal preferences. The areca nut alkaloids (arecoline, arecaidine, guvacine, and guvacoline), and tobacco alkaloids (nicotine, nornicotine) undergo nitrosation during chewing in the oral cavity with the presence of nitrite and thiocyanate and endogenously. Among the nitrosation products generated areca nut-derived nitrosamine (ADNA): 3-(methylnitrosamino) Propionitrile (MNPN) and the two tobacco-specific nitrosamines (TSNAs); N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) (NNK) are considered Group 1 human carcinogens. The slaked lime increases pH, reactive oxygen species (ROS) generation, and inflammation further lead to oral potentially malignant disorders (OPMD). The juice swallowed results in carcinogenicity, mutagenicity, and toxicity in the gastrointestinal tract including hepatocytic carcinoma, stomach, and colon cancer. Areca nut pre-treatments (sun drying, roasting, boiling, and fermentation) increase the quid metabolism, and reduce the arecoline content and associated risks. We review biochemical carcinogenesis of betel quid ingredients and synergic adverse effects and possible mechanism of carcinogenesis of betel quid in the oral cavity and gastrointestinal tract to understand the implication of polyphenols and alkaloids of areca nut and betel quid on carcinogenic nitrosamine formation under oral, gastric, and intestinal conditions.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111383"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myriscagayanone C, a new compound from the fruit of myristica cagayanensis, inhibits fMLP-induced respiratory bursts by specifically preventing Akt translocation in human neutrophils.","authors":"Hsiang-Ruei Liao, Chen-Lung Chen, Yu-Yao Kao, Fu-Chao Liu, Ching-Ping Tseng, Jih-Jung Chen","doi":"10.1016/j.cbi.2024.111357","DOIUrl":"10.1016/j.cbi.2024.111357","url":null,"abstract":"<p><p>Neutrophils that are overactivated can cause inflammatory diseases. Neutrophils possess various surface receptors, including G-protein-coupled chemoattractant receptors, which assist in recognizing pathogen attacks and the inflammatory environment. Therefore, targeting G-protein-coupled chemoattractant receptors and their downstream molecules is important for preventing abnormal neutrophil activation. This study examines the effects and underlying mechanism of myriscagayanone C, a new compound obtained from the fruit of myristica cagayanensis, on neutrophil respiratory burst induced by fMLP. The immunoblotting assay was conducted to assess the mechanisms by which myriscagayanone C inhibits fMLP-induced respiratory burst by disrupting the translocation of Akt to the cellular membrane. Briefly, myriscagayanone C suppressed the production of superoxide anions induced by fMLP on human neutrophils in a concentration-dependent manner (IC₅₀: 4.73 ± 0.68 μM). Myriscagayanone C blocked fMLP-induced Akt translocation to the cell membrane, inhibiting Akt^T308 and Akt^S473 phosphorylation by PDK1^Y373/376 and mTOR^S2481, respectively. Myriscagayanone C inhibited fMLP-induced p47^phox phosphorylation and translocation. Myriscagayanone C did not inhibit the activity of PI3K, the amount of phosphatidylinositol (3, 4, 5)-trisphosphate, or the translocation of phosphorylated-PDK1^Y373/376 and -mTOR^S2481 to the membrane. Myriscagayanone C did not inhibit fMLP-induced PKC, Src, ERK1/2, p38 phosphorylation, and intracellular calcium mobilization. Myriscagayanone C did not inhibit the chemotaxis and CD11b expression induced by fMLP. Myriscagayanone C did not inhibit PMA-induced superoxide anion production and neutrophil extracellular trap formation. According to this data, myriscagayanone C inhibits fMLP-induced neutrophil superoxide anion production by interrupting the translocation of Akt to the plasma membrane, which affects the NADPH oxidase activity by preventing p47^phox phosphorylation and translocation.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111357"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Equol promotes osteogenic differentiation of hPDLSCs by inhibiting oxidative stress via IL1B/NF-κB/CXCL1 signaling axis.","authors":"Xiaoxi Jiang, Xiao Chen, Lingxiao He, Dan Qin, Minhai Nie, Chunhui Li, Xuqian Liu","doi":"10.1016/j.cbi.2024.111367","DOIUrl":"10.1016/j.cbi.2024.111367","url":null,"abstract":"<p><p>Oxidative stress (OS) inhibits the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). Equol (Eq), a phytoestrogen, exhibits notable antioxidant properties and potential for preventing osteoporosis. However, the research on the regulatory effects of Eq on stem cell osteogenesis remains limited. This investigation aimed to identify whether Eq could protect the osteogenic potential of hPDLSCs under H₂O₂-induced oxidative microenvironment. We employed a series of assays, including CCK-8, DCFH-DA, ALP staining, ARS, RT-qPCR, and Western Blotting, to assess the changes in cell viability, antioxidant capacity, and osteogenic potential following H₂O₂ and Eq treatments. Our findings indicated that low concentrations of Eq had no cytotoxic effects on hPDLSCs and promoted their proliferation. Eq pre-treatment (0.5 μmol/L) partially counteracted the inhibitory effect of H₂O₂, reduced the generation of reactive oxygen species, and increased glutathione levels, thereby inhibiting oxidative damage. Eq suppressed the H₂O₂-induced inhibition of osteogenic differentiation, presenting as restoring the alkaline phosphatase levels and calcium nodule formation, as well as by upregulating the expression of BMP2 and RUNX2. Furthermore, bioinformatics analysis in this study suggested that the IL1B/NF-κB/CXCL1 signaling pathway might be a key pathway for Eq's enhancement of osteogenic differentiation potential of hPDLSCs under OS conditions. The activation of this axis by H₂O₂, which Eq can alleviate, was confirmed by validation experiments. This study provides new insights into the potential therapeutic application of Eq in alveolar bone resorption and bone regeneration research.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111367"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platinum as both a drug and its modulator - Do platinum nanoparticles influence cisplatin activity?","authors":"Patrycja Bełdzińska, Barbara Galikowska-Bogut, Marcin Zakrzewski, Katarzyna Bury, Marzena Jamrógiewicz, Dariusz Wyrzykowski, Grzegorz Gołuński, Rafał Sądej, Jacek Piosik","doi":"10.1016/j.cbi.2024.111365","DOIUrl":"10.1016/j.cbi.2024.111365","url":null,"abstract":"<p><p>Breast cancer was the most frequent cause of cancer death in females in 2022. Despite the development of personalized therapies, chemotherapy frequently remains the only available treatment method. However, the administration of classic antineoplastic drugs, like cisplatin (CDDP), often causes severe side effects and may lead to drug resistance making the therapy inefficient. Therefore, there is a great need for new, effective treatment regimens development. For this reason, we applied platinum nanoparticles (PtNPs) to verify if they can influence the CDDP activity with particular emphasis on the differences due to nanoparticles' sizes. We employed a broad spectrum of physicochemical methods, including Dynamic Light Scattering, Atomic Force Microscopy, Isothermal Titration Calorimetry, Fourier Transform Infrared Spectroscopy, and Near Infrared Spectroscopy and also Differential Scanning Calorimetry, to characterize the possible interactions between nanoparticles and CDDP. Moreover, the impact of PtNPs on CDDP biological activity was investigated using the Ames mutagenicity test on Salmonella enterica serovar Typhimurium TA102 and MTT assay on two breast cancer cell lines MDA-MB-231 and SKBR3. The obtained results revealed PtNPs direct interactions with CDDP dependent on the nanoparticles' size. Despite the lack of explicit confirmation of PtNPs aggregation by AFM imaging and DLS, further physicochemical methods indicated structural changes between nanoparticles alone and PtNPs-CDDP mixtures. Moreover, the biological assays confirmed that PtNPs decrease CDDP mutagenicity and also slightly increase its cytotoxicity on the chosen cell lines. The latter effects are ambiguous, nevertheless, provide a valuable basis for further research.</p>","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111365"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}