Archives of biochemistry and biophysics最新文献

{"title":"Synthesis, anti-proliferation, apoptosis induction in breast cancer cells, and aromatase inhibition of coumarin-triazole hybrids: In vitro and in silico studies","authors":"Amporn Saekee ,&nbsp;Pichjira Sooknual ,&nbsp;Sakdiphong Punpai ,&nbsp;Veda Prachayasittikul ,&nbsp;Sakchai Hongthong ,&nbsp;Wanlaya Tanechpongtamb ,&nbsp;Supaluk Prachayasittikul ,&nbsp;Somsak Ruchirawat ,&nbsp;Virapong Prachayasittikul ,&nbsp;Ratchanok Pingaew","doi":"10.1016/j.abb.2025.110308","DOIUrl":"10.1016/j.abb.2025.110308","url":null,"abstract":"<div><div>Breast cancer is one of the most common cancers found in women worldwide. Besides the availability of clinical drugs, drug resistance and considerable side effects are concerning issues driven the needs for the discovery of novel anticancer agents. Aromatase inhibition is one of the effective strategies for management of hormone-dependent breast cancer. Triazole, coumarin, and isatin are heterocyclic scaffolds holding great attention in the field of drug design. Molecular hybridization is a well-known strategy to achieve new molecules with improved potency and properties. Herein, a set of 27 triazole-based hybrids (i.e., coumarin-triazoles series <strong>5</strong>–<strong>6</strong> and isatin-triazoles series <strong>7</strong>) were synthesized and investigated for their anti-proliferation, apoptosis induction, and aromatase inhibitory potentials. Anti-proliferative study against the hormone-dependent breast cancer (T47D) cell line indicated that coumarin-triazoles <strong>5h</strong> (R=NO₂) and <strong>6i</strong> (R=SO₂NH₂) were the two most potent antiproliferative agents. Particularly, compound <strong>5h</strong> showed comparable potency and superior selectivity index than that of the reference drug, doxorubicin. Moreover, the coumarin-triazole <strong>5h</strong> induced cellular apoptosis of the estrogen-dependent breast cancer (MCF-7) cells. Additionally, findings from the aromatase inhibitory assay suggested four compounds as potential aromatase inhibitors (i.e., <strong>5i</strong>, <strong>6f</strong>, <strong>6g</strong> and <strong>6i,</strong> IC₅₀ = 1.4–2.4 μM). Two QSAR models with preferable predictive performances were constructed to reveal key properties influencing antiproliferative and aromatase inhibitory effects. Molecular docking was conducted to elucidate the possible binding modalities against the target aromatase enzyme. Key structural features essential for the binding were highlighted. Moreover, the drug-like properties of top-ranking compounds were assessed to ensure their possibilities for successful development.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110308"},"PeriodicalIF":3.8,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998872","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":"Acer tegmeutosum Maxim extract alleviates acute alcohol-induced liver disease and regulates gut microbiota dysbiosis in mice","authors":"Jianan Wang ,&nbsp;Aqing Jian ,&nbsp;Depeng Sun ,&nbsp;Mingxun Cui ,&nbsp;Chunxiang Piao ,&nbsp;Juan Wang ,&nbsp;Baide Mu ,&nbsp;Tingyu Li ,&nbsp;Guanhao Li ,&nbsp;Hongmei Li","doi":"10.1016/j.abb.2025.110314","DOIUrl":"10.1016/j.abb.2025.110314","url":null,"abstract":"<div><div><em>Acer tegmentosum</em> Maxim (AT) has a variety of pharmacological activities, however, the effects of AT on liver injury and gut microbiota in alcoholic liver disease (ALD) mice is still unclear. This study aimed to evaluate the preventive effect of AT extract on acute alcoholic liver disease. Six-week-old male C57BL/6J mice were randomly divided into 6 groups. Each group was intragastrically treated saline or different concentration of AT extract solution for 5 weeks continuously. After the last gavage, except for the NC group, all the other groups were gavaged twice with 56 % alcohol to establish the acute ALD model and biochemical indexes, histopathological, and gut microbiota were analyzed. Established an acute ALD mouse model and detected serum, liver oxidation levels, and alcohol metabolism-related gene expressions. Through 16S rRNA sequencing, analyzed gut microbiota, explored the relationship between gut microbiota and liver indicators. AT extract significantly decreased lipid levels, promoted ADH, ALDH, and increased the antioxidant activities. Meanwhile, AT extract significantly downregulated the expression of lipid oxidation and inflammatory factors, upregulated alcohol metabolism genes. In addition, 16S rRNA sequencing and analysis showed that AT extract effectively regulated the gut microbiota diversity of ALD mice, significantly improved the structural disturbance of intestinal microflora. AT extract regulated gut microbiota and had a strong correlation with serum, liver-related indexes, and gene expression levels. All these results showed that AT can alleviate alcohol induced liver injury by regulating oxidative stress, inflammatory response, alcohol metabolism, and gut microbiota disorder.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110314"},"PeriodicalIF":3.8,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997967","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":"Hypoxia-inducible factor-1α inhibitor promotes non-alcoholic steatohepatitis development and increases hepatocellular lipid accumulation via TSKU upregulation","authors":"Renli Zeng ,&nbsp;Yuxin Wang ,&nbsp;Jielu Wen ,&nbsp;Zhipeng Cen ,&nbsp;Tengyao Wang ,&nbsp;Meng Duan ,&nbsp;Xiuyi Huang ,&nbsp;Zhengde Zhao ,&nbsp;Zhongyu Zhang ,&nbsp;Chuan Yang ,&nbsp;Sifan Chen","doi":"10.1016/j.abb.2025.110313","DOIUrl":"10.1016/j.abb.2025.110313","url":null,"abstract":"<div><div>Non-alcoholic steatohepatitis (NASH) is the progressive form of non-alcoholic fatty liver disease (NAFLD) which is the most common chronic liver disease worldwide. Hypoxia-inducible factor-1α (HIF1α) inhibitor is emerging as a promising therapeutic strategy for diseases. However, the role of HIF1α inhibitor in NASH is still unclear. A choline-deficient, <span>l</span>-amino acid-defined, high-fat diet (CDAHFD) -induced NASH mouse model was established to identify the impacts of HIF1α inhibitor KC7F2 on the development of NASH. We found that KC7F2 treatment substantially aggravated lipid accumulation, inflammation, and fibrosis in the liver of NASH mice presumably via increasing Tsukushi (TSKU) expression in the liver. Mechanistically, KC7F2 up-regulated expression of TSKU in hepatocyte <em>in vitro</em>, which led to increased hepatocellular lipid accumulation and was reversed when TSKU was knockdown in hepatocyte. Our findings indicated that HIF1α inhibitor promotes the development of NASH presumably via increasing TSKU expression in the liver, suggesting that HIF1α attenuates NASH, and that we should assess the potential liver toxicity when use HIF1α inhibitor or medicines that can decrease the expression of HIF1α to therapy other diseases.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110313"},"PeriodicalIF":3.8,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998851","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":"Degrading mutant IDH1 employing a PROTAC-based approach impairs STAT3 activation","authors":"Hashnu Dutta ,&nbsp;Nishant Jain","doi":"10.1016/j.abb.2024.110281","DOIUrl":"10.1016/j.abb.2024.110281","url":null,"abstract":"<div><div>Heterozygous mutations in IDH1 (isocitrate dehydrogenase 1) are found in most grade II and III brain tumors. A slew of mutant IDH1 inhibitors were identified soon after the discovery of IDH1 mutations in brain tumors. But recent reports show that mutant IDH1 inhibitors reverse therapeutic vulnerabilities and activate the oncogenic transcription factor STAT3 in mutant IDH1-expressing cells. Thus, inhibiting mutant IDH1 using mutant IDH1-specific inhibitors can result in drug resistance. Therefore, to block mutant IDH1, it is imperative to identify alternative modes of therapy. In these lines, recent findings show that <u>PRO</u>teolysis <u>TA</u>rgeting <u>C</u>himera (PROTAC) molecules can be designed to degrade target proteins in cancer cells. However, it is unknown whether degrading mutant IDH1 leads to STAT3 activation. Therefore, in this study, we asked if degrading mutant IDH1 by employing a PROTAC-based approach leads to STAT3 activation. To answer the question, we adopted the dTAG system, where we fused FKBP12^F36V to mutant IDH1 proteins and used the FKBP12^F36V-specific PROTAC, dTAG-13, to degrade mutant IDH1-FKBP12^F36V. We assessed STAT3 activation in dTAG-13-treated cells expressing mutant IDH1-FKBP12^F36V. We found that fusing FKBP12^F36V-HA to mutant IDH1 phenocopies mutant IDH1 with similar expression levels, enzyme activity, and cellular localization. We observed that dTAG-13 degrades mutant IDH1-FKBP12^F36V-HA in a dose- and time-responsive manner. Unlike inhibiting, degrading mutant IDH1-FKBP12^F36V-HA did not lead to pSTAT3-Y705 activation. We conclude that degrading mutant IDH1 by employing a PROTAC-based approach impairs STAT3 activation. Based on these observations, we suggest that mutant IDH1-specific PROTACs can be developed to degrade mutant IDH1 in gliomas.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110281"},"PeriodicalIF":3.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998379","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":"Mechanisms and applications of bacterial luciferase and its auxiliary enzymes","authors":"Chadaporn Kantiwiriyawanitch ,&nbsp;Ubolsree Leartsakulpanich ,&nbsp;Pimchai Chaiyen ,&nbsp;Ruchanok Tinikul","doi":"10.1016/j.abb.2025.110307","DOIUrl":"10.1016/j.abb.2025.110307","url":null,"abstract":"<div><div>Bacterial luciferase (LuxAB) catalyzes the conversion of reduced flavin mononucleotide (FMNH⁻), oxygen, and a long-chain aldehyde to oxidized FMN, the corresponding acid and water with concomitant light emission. This bioluminescence reaction requires the reaction of a flavin reductase such as LuxG (<em>in vivo</em> partner of LuxAB) to supply FMNH⁻ for the LuxAB reaction. LuxAB is a well-known self-sufficient luciferase system because both aldehyde and FMNH⁻ substrates can be produced by the associated enzymes encoded by the genes in the <em>lux</em> operon, allowing the system to be auto-luminous. This makes it useful for <em>in vivo</em> applications. Structural and functional studies have long been performed in efforts to gain a better understanding of the LuxAB reaction. Recently, continued exploration of the LuxAB reaction have elucidated the mechanisms of C4a-hydroperoxyflavin formation and identified key catalytic residues such as His44 that facilitates the generation of flavin intermediates important for light generation. Advancements in protein engineering and synthetic biology have improved the bioluminescence properties of LuxAB. Various applications of LuxAB for bioimaging, bioreporters, biosensing in metabolic engineering and real-time monitoring of aldehyde metabolites in biofuel production pathways have been developed during the last decade. Challenging issues such as achieving red-shifted emissions, optimizing the signal intensity and identifying mechanisms related to the generation of light-emitting species remain to be explored. Nevertheless, LuxAB continues to be a promising tool for diverse biotechnological and biomedical applications.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110307"},"PeriodicalIF":3.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998855","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":"c-FLIP/Ku70 complex; A potential molecular target for apoptosis induction in hepatocellular carcinoma","authors":"Yasamin Haghir-Sharif-Zamini ,&nbsp;Arezoo Khosravi ,&nbsp;Moustapha Hassan ,&nbsp;Ali Zarrabi ,&nbsp;Massoud Vosough","doi":"10.1016/j.abb.2025.110306","DOIUrl":"10.1016/j.abb.2025.110306","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide and the most common form of liver cancer. Despite global efforts toward early diagnosis and effective treatments, HCC is often diagnosed at advanced stages, where conventional therapies frequently lead to resistance and/or high recurrence rates. Therefore, novel biomarkers and promising medications are urgently required. Epi-drugs, or epigenetic-based medicines, have recently emerged as a promising therapeutic modality. Since the epigenome of the cancer cells is always dysregulated and this is followed by apoptosis-resistance, reprogramming the epigenome of cancer cells by epi-drugs (such as HDAC inhibitors (HDACis), and DNMT inhibitors (DNMTis)) could be an alternative approach to use in concert with established treatment protocols. C-FLIP, an anti-apoptotic protein, and Ku70, a member of the DNA repair system, bind together and make a cytoplasmic complex in certain cancers and induce resistance to apoptosis. Many epi-drugs, such as HDACis, can dissociate this complex through Ku70 acetylation and activate cellular apoptosis. The novel compounds for dissociating this complex could provide an innovative insight into molecular targeted HCC treatments. In this review, we address the innovative therapeutic potential of targeting c-FLIP/Ku70 complex by epi-drugs, particularly HDACis, to overcome apoptosis resistance of HCC cells. This review will cover the mechanisms by which the c-FLIP/Ku70 complex facilitates cancer cell survival, the impact of epigenetic alterations on the complex dissociation, and highlight HDACis potential in combination therapies, biomarker developments and mechanistic overviews. This review highlights c-FLIP ubiquitination and Ku70 acetylation levels as diagnostic and prognostic tools in HCC management.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110306"},"PeriodicalIF":3.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998880","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":"Live-cell FRET assay on the stoichiometry and affinity of the YAP complexes in MCF-7 cells","authors":"Yongtong Zhan ,&nbsp;Lingao Dai ,&nbsp;Ze Fu ,&nbsp;Xuhong Fan ,&nbsp;Xin Li ,&nbsp;Guihao Wu ,&nbsp;Yue Ni ,&nbsp;Ge Wu ,&nbsp;Tongsheng Chen ,&nbsp;Xiaoping Wang","doi":"10.1016/j.abb.2025.110305","DOIUrl":"10.1016/j.abb.2025.110305","url":null,"abstract":"<div><div>Yes-associated protein (YAP), a focal point of current biological research, is involved in regulating various life processes. In this report, live-cell fluorescence resonance energy transfer (FRET) imaging was employed to unravel the YAP complexes in MCF-7 cells. Fluorescence imaging of living cells co-expressing CFP (cyan fluorescent protein)-YAP and YFP (yellow fluorescent protein)-LATS1 (large tumor suppressor 1) plasmids revealed that YAP promoted LATS1 oligomerization around mitochondria. Moreover, FRET two-hybrid assay showed that YAP directly interacted with LATS1 to form dimer. Similarly, we found that YAP directly interacted with large tumor suppressor 2 (LATS2) to form a heterotrimer with 1:2 in cytoplasm and around mitochondria. In addition, YAP directly interacted with angiomotin (AMOT) to form a heterodimer in cytoplasm. However, YAP did not interact with O-linked N-acetylglucosamine transferase (OGT). Furthermore, FRET assay also indicated that YAP exhibited a higher affinity with AMOT, followed by LATS1, and least with LATS2. In summary, YAP directly interacts with LATS1 and AMOT to form a heterodimer, with LATS2 to form a heterotrimer with 1:2, and shows a preference for binding to AMOT, followed by LATS1, and lastly LATS2, providing new insights into the Hippo-YAP signaling pathway.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110305"},"PeriodicalIF":3.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998853","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":"Unveiling the cyclopropyl appended acyl thiourea derivatives as antimicrobial, α-amylase and proteinase K inhibitors: Design, synthesis, biological evaluation, molecular docking, DFT and ADMET studies","authors":"Hina Zaman ,&nbsp;Aamer Saeed ,&nbsp;Hammad Ismail ,&nbsp;Muhammad Rashid","doi":"10.1016/j.abb.2025.110304","DOIUrl":"10.1016/j.abb.2025.110304","url":null,"abstract":"<div><div>Acyl thiourea scaffolds are frequently employed in drug development to discern unique and essential therapies for the eradication of the most challenging diseases. Hence, we developed a library of novel cyclopropyl incorporating acyl thiourea derivatives (<strong>4a-j</strong>) and evaluated their antimicrobial, <em>α</em>-amylase, and proteinase K inhibition potential. Compound (<strong>4h</strong>) (4-methoxy) demonstrated the strongest <em>α</em>-amylase inhibition (IC₅₀ = 1.572 ± 0.017 μM), while compound (<strong>4j</strong>) (3,4,5-trimethoxy) exhibited potent proteinase K inhibition (IC₅₀ = 1.718 ± 0.061 μM), comparable to the standard acarbose (IC₅₀ = 1.063 ± 0.013 μM) and phenyl methyl sulfonyl fluoride (IC₅₀ = 0.119 ± 0.014 μM). The unsubstituted compound (<strong>4a</strong>) emerged as the most potent antifungal agent (17 mm zone of inhibition), outperforming the positive control Terbinafine (zone of inhibition 16 mm). These compounds (<strong>4a-j</strong>) also displayed moderate antibacterial activity. SAR analysis revealed the influences of various substitutions on the acyl thiourea scaffold. Computational studies, including DFT, molecular docking, and ADMET predictions, supported the biological findings and identified these compounds as promising inhibitors of <em>α</em>-amylase, proteinase K, and microbial pathogens.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110304"},"PeriodicalIF":3.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998875","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":"Gymnema saponin-induced lipid flip-flop identifies rigid membrane phenotype of methicillin resistant S. aureus and enhances it's antibiotic susceptibility","authors":"Gayatree Panda ,&nbsp;Swagatika Dehury ,&nbsp;Himadri Gourav Behuria ,&nbsp;Bijesh Kumar Biswal ,&nbsp;Ashis Kumar Jena ,&nbsp;Indrani Mohanty ,&nbsp;Sasmita Hotta ,&nbsp;Santosh Kumar Padhi ,&nbsp;Santosh Kumar Sahu","doi":"10.1016/j.abb.2025.110303","DOIUrl":"10.1016/j.abb.2025.110303","url":null,"abstract":"<div><div>Our previous study revealed that lipid flip-flop inducing phytochemicals from <em>Gymnema sylvestre</em> increase membrane permeability of antimicrobials in <em>S</em>. <em>aureus</em>. However, their lipid flipping and membrane permeabilizing effect on methicillin resistant <em>S</em>. <em>aureus</em> (MRSA) membrane that has intrinsically higher aminoacylated lipid content compared to methicillin sensitive <em>S</em>. <em>aureus</em> (MSSA) is poorly characterized. <em>Gymnema</em> saponins, gymnemic acid I and IV significantly increased the antibiotic susceptibility in both MSSA and MRSA. MRSA exhibited a rigid membrane with lipid diffusion coefficient 0.0002 μm²/s compared to the MSSA membrane lipids with diffusion coefficient 1.48 μm²/s. Further, unlike MSSA, MRSA cells inhibited fusion of fluid liposomes with their plasma membrane. <em>In vitro</em> assay on reconstituted membrane vesicles revealed that <em>Gymnema</em> saponins induced 60 % lipid flipping in MSSA membrane compared to only 20 % lipid flipping in MRSA, indicating significantly lower <em>Gymnema</em> saponin-induced <em>trans</em>-bilayer lipid mobility in MRSA. <em>Gymnema</em> saponins induced significantly lower crystal violet uptake, release of cellular protein, cell shrinkage and lysis in MRSA compared to MSSA. <em>Gymnema</em> saponins led to dose-dependent inhibition of lipid-aminoacylation in both MSSA and MRSA making their membranes more negative compared to untreated control cells. <em>In silico</em> analysis reveals binding of both gymnemic acid I and IV to multiple peptide resistance factor (binding energy ∼ 7.5 kCal), the protein responsible for lipid aminoacylation in <em>S</em>. <em>aureus</em>. For the first time, our study reveals that MRSA membrane with higher aminoacyl-PG compared to MSSA shows significantly lower rate of diffusion and <em>trans</em>-bilayer flip-flop of lipids. Further, gymnemic acids are useful probes for identification, characterization and drug sensitization of rigid membrane MRSA phenotypes.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110303"},"PeriodicalIF":3.8,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977294","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":"The effectiveness of prolonged hypothermic preservation of isolated rat hearts using oxygen, medical nitrous oxide and carbon monoxide gas mixtures","authors":"Evgeniy L. Gagarinskiy,&nbsp;Mars G. Sharapov,&nbsp;Ruslan G. Goncharov,&nbsp;Artem E. Gurin,&nbsp;Svetlana V. Ugraitskaya,&nbsp;Eugeny E. Fesenko","doi":"10.1016/j.abb.2025.110295","DOIUrl":"10.1016/j.abb.2025.110295","url":null,"abstract":"<div><div>The possibility of using an oxygen-nitrous oxide mixture for prolonged hypothermic preservation of rat heart for 24 h was investigated. A comparative analysis of restoration of functional activity of hearts in the groups of 24-h preservation at +4 °C with different gases (O₂, N₂) and gas mixtures (CO + O₂, N₂O + O₂, N₂+O₂, N₂O + N₂) was carried out. It was shown that the presence of oxygen in the gas mixture was the key factor for heart preservation. No stable heart preservation was observed in oxygen-free mixtures. At the same time, preservation in pure oxygen showed a significantly lower level of cardiac recovery compared to preservation in gas mixtures O₂+CO (6.5 atm.) and O₂+N₂O (6.5 atm.). LVDP (left ventricular developed pressure) values were 30 ± 19 mmHg and 46 ± 9 mmHg, respectively, with no significant differences found. The decrease in LDVP after 24 h of storage was 26–40 % of the intact control. The results obtained indicate the presence of pronounced synergistic effects of both gases during 24-h heart preservation, which is confirmed by data of marker genes Nfe2l2, Nox1, Prdx1, Hif1a, Nos2, Slc2a4, Ucp-1, Jun, Casp3 expression analysis and myocardial infarction damage level data. The more frequent occurrence of arrhythmias was observed in the oxygen-nitrous oxide group compared with the CO group, and the mechanism of this phenomenon is unclear. Nevertheless, the already medically approved N₂O + O₂ gas mixture could serve as a balanced choice for future improvements, offering a shorter duration of cardiac preservation compared to the CO + O₂ mixture, while ensuring safety in its use.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110295"},"PeriodicalIF":3.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969503","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}