Biochimica et biophysica acta. General subjects最新文献

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Novel pilot study on plasma metabolites and biomarkers in a rat model of silica-induced lung inflammation and fibrosis 关于二氧化硅诱发肺部炎症和纤维化大鼠模型中血浆代谢物和生物标志物的新型试验研究。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-10-22 DOI: 10.1016/j.bbagen.2024.130729
Daniela Mokrá , Jana Adamčáková , Soňa Bálentová , Romana Barošová , Juliana Hanusrichterová , Nela Žideková , Pavol Mikolka , Juraj Mokrý , Martin Kertys
{"title":"Novel pilot study on plasma metabolites and biomarkers in a rat model of silica-induced lung inflammation and fibrosis","authors":"Daniela Mokrá ,&nbsp;Jana Adamčáková ,&nbsp;Soňa Bálentová ,&nbsp;Romana Barošová ,&nbsp;Juliana Hanusrichterová ,&nbsp;Nela Žideková ,&nbsp;Pavol Mikolka ,&nbsp;Juraj Mokrý ,&nbsp;Martin Kertys","doi":"10.1016/j.bbagen.2024.130729","DOIUrl":"10.1016/j.bbagen.2024.130729","url":null,"abstract":"<div><div>Silica-induced lung damage may be associated with changes in distinct metabolites potentially serving as biomarkers. Due to the lack of metabolomic data from animal models, this pilot study aimed to evaluate changes in markers of inflammation and fibrosis, as well as plasma metabolites in rats at 14 and 28 days after silica instillation.</div><div>Adult male Wistar rats were administered a single oropharyngeal intratracheal dose of silica suspension or sterile saline in controls. Selected markers of inflammation, oxidative stress, fibrosis, and cell counts in blood and bronchoalveolar lavage fluid have been evaluated. Finally, plasma metabolites were detected using a targeted metabolomics approach with an MxP® Quant 500 kit.</div><div>Silica instillation induced noticeable inflammatory, oxidative, and fibrotic changes in lung tissue within the first 14 days. During the next two weeks, the shifts in some markers were further accentuated. After exposure to silica, the metabolomic analysis identified significant changes in metabolites associated with lipid metabolism, biogenic amines, amino acid derivatives, carboxylic acids, bile acids, putrescine, glycosylceramides, and acylcarnitines.</div><div>This pilot study provides initial evidence that significant alterations in plasma metabolite profiles accompany silica-induced lung injury in rats. These findings suggest a possible systemic impact, particularly on lipid metabolism, and indicate the urgent need for a deeper understanding of the metabolic reprogramming associated with silica-induced lung injury to pave the way for the discovery of novel biomarkers.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493918","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}
引用次数: 0
A comparative study of bioenergetic metabolism on mammary epithelial cells from humans and Göttingen Minipigs 人类和哥廷根小型猪乳腺上皮细胞生物能代谢比较研究
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-10-20 DOI: 10.1016/j.bbagen.2024.130728
Cristina Algieri , Chiara Bernardini , Debora La Mantia , Fabiana Trombetti , Monica Forni , Salvatore Nesci
{"title":"A comparative study of bioenergetic metabolism on mammary epithelial cells from humans and Göttingen Minipigs","authors":"Cristina Algieri ,&nbsp;Chiara Bernardini ,&nbsp;Debora La Mantia ,&nbsp;Fabiana Trombetti ,&nbsp;Monica Forni ,&nbsp;Salvatore Nesci","doi":"10.1016/j.bbagen.2024.130728","DOIUrl":"10.1016/j.bbagen.2024.130728","url":null,"abstract":"<div><div>Mammary epithelial cells (MECs) of humans (h) and Göttingen Minipigs (mp) were analyzed to compare their ability to perform ATP production by oxidative phosphorylation and glycolysis. The ATP production under basal and stressor situations highlights the same metabolic potential of both primary cell lines. However, quantitively the ATP production rate of hMECs was higher than mpMECs. Conversely, oxidative cell respiration in mpMECs exploits a maximum respiratory capacity to support pathophysiological circumstances or stress conditions that could require an excessive effort of cell metabolism. Since mpMECs primarily utilize an oxidative metabolism similar to hMECs, the metabolic characterization conducted allows us to confirm that mpMECs represent a potential alternative cellular model in the translational medicine approach.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493919","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}
引用次数: 0
Effect of modification of siRNA molecules delivered with aminopropylsilanol nanoparticles on suppression of A/H5N1 virus in cell culture 用氨基丙基硅烷醇纳米颗粒递送的 siRNA 分子的修饰对抑制细胞培养中的 A/H5N1 病毒的影响。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-10-20 DOI: 10.1016/j.bbagen.2024.130727
Marina Repkova , Oleg Mazurkov , Ekaterina Filippova , Maria Protsenko , Natalia Mazurkova , Maria Meschaninova , Asya Levina , Valentina Zarytova
{"title":"Effect of modification of siRNA molecules delivered with aminopropylsilanol nanoparticles on suppression of A/H5N1 virus in cell culture","authors":"Marina Repkova ,&nbsp;Oleg Mazurkov ,&nbsp;Ekaterina Filippova ,&nbsp;Maria Protsenko ,&nbsp;Natalia Mazurkova ,&nbsp;Maria Meschaninova ,&nbsp;Asya Levina ,&nbsp;Valentina Zarytova","doi":"10.1016/j.bbagen.2024.130727","DOIUrl":"10.1016/j.bbagen.2024.130727","url":null,"abstract":"<div><div>The application of siRNAs as antiviral agents is limited by several obstacles including their poor penetration into cells and instability in biological media. To overcome these problems, we used non-agglomerated aminopropylsilanol nanoparticles (NP) to deliver siRNA into cells. All studied siRNAs had identical nucleoside sequences comprising phosphodiester or phosphorothioate (PS) internucleotide groups and the 2’-OMe and/or 2’-F groups in nucleoside units at different positions of RNA. The siRNA molecules were attached to NP, thus forming the NP-siRNA nanocomplexes. We studied the effect of siRNA modification in the nanocomplexes on suppressing the highly pathogenic influenza A/H5N1 virus replication. The results demonstrated that all siRNA-containing nanocomplexes inhibited the replication of the A/H5N1 virus by 1–3 orders of magnitude. The nanocomplexes containing partially modified siRNAs exhibited the most pronounced inhibition with an efficacy of 900-fold. This result was achieved by using siRNA consisting of the canonical 19-bp RNA duplex with the 3′-dTdT dangling ends, with the antisense strand in this duplex being protected from endonucleases (one U<sup>Me</sup>A site within the strand). The additional modifications of siRNA reduce their antiviral activity. Promising sense strands for loading into the RISC complex are likely to be phosphodiester sequences that contain dTdT at the 3′ end (such as S<sub>4</sub>) to be protected against exonucleases. The sense strands of this type can probably be the most suitable for designing siRNAs as therapeutic agents. The proposed NP-siRNA nanocomplexes that consisted of low toxic and non-agglomerated aminopropylsilanol nanoparticles and siRNA molecules could be hopeful agents for gene silencing.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493920","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}
引用次数: 0
Evaluating cholinesterases inhibition by BAC and DDAC biocides: A combined experimental and theoretical approach 评估 BAC 和 DDAC 生物杀灭剂对胆碱酯酶的抑制作用:实验与理论相结合的方法
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-10-19 DOI: 10.1016/j.bbagen.2024.130726
Lynn Mouawad , Jeremy Esque , Isabelle André , Georges Istamboulie , Gaëlle Catanante , Thierry Noguer
{"title":"Evaluating cholinesterases inhibition by BAC and DDAC biocides: A combined experimental and theoretical approach","authors":"Lynn Mouawad ,&nbsp;Jeremy Esque ,&nbsp;Isabelle André ,&nbsp;Georges Istamboulie ,&nbsp;Gaëlle Catanante ,&nbsp;Thierry Noguer","doi":"10.1016/j.bbagen.2024.130726","DOIUrl":"10.1016/j.bbagen.2024.130726","url":null,"abstract":"<div><div>Disinfectant biocides are chemicals that are heavily used for disinfection purposes in households, hospitals, and agrifood industry. The most common type of biocides are quaternary ammonium compounds (QAs), notably benzalkonium chloride (BAC) and didecyldimethylammonium chloride (DDAC), which have been shown to inhibit cholinesterases. This study aims to evaluate the effect of these biocides towards different cholinesterases using both enzyme inhibition and molecular docking experiments. Acetylcholinesterase (AChE) from <em>Drosophila melanogaster</em> (DM-AChE), <em>Electrophorus electricus</em> (EE-AChE), bovine erythrocytes (BE-AChE) and butyrylcholinesterase from horse serum (BChE) were selected for this study. Using a colorimetric assay, all these enzymes were shown to be inhibited in a competitive form by both biocides, BAC and DDAC, with the exception of DM-AChE, which was inhibited in a non-competitive manner by BAC. Molecular docking experiments enabled to identify structural determinants involved in the different modes of inhibition observed. More particularly, our results suggest that non-competitive inhibition of DM-AChE by BAC could be related to the binding of the inhibitor into a more extended active site compared to other cholinesterases.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457046","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}
引用次数: 0
Photosensitizing metal–organic framework nanoparticles combined with tumor-sensitization strategies can enhance the phototherapeutic effect upon medullary thyroid carcinoma 光敏金属有机框架纳米粒子与肿瘤增敏策略相结合,可增强对甲状腺髓样癌的光疗效果。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-10-19 DOI: 10.1016/j.bbagen.2024.130725
Yingqi Feng , Qiyu Jiang , Xue Ma , Huiwei Sun , Yantao Chai , Xiaojuan Li , Zhijie Wang , Fan Feng
{"title":"Photosensitizing metal–organic framework nanoparticles combined with tumor-sensitization strategies can enhance the phototherapeutic effect upon medullary thyroid carcinoma","authors":"Yingqi Feng ,&nbsp;Qiyu Jiang ,&nbsp;Xue Ma ,&nbsp;Huiwei Sun ,&nbsp;Yantao Chai ,&nbsp;Xiaojuan Li ,&nbsp;Zhijie Wang ,&nbsp;Fan Feng","doi":"10.1016/j.bbagen.2024.130725","DOIUrl":"10.1016/j.bbagen.2024.130725","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) utilizing metal-organic frameworks (MOFs) has developed as a new and efficacious treatment for malignant tumors located on the surface of the human body. In order to achieve more effective PDT treatment outcomes, the traditional method has been to increase the intensity of the laser irradiation, but this approach can easily lead to tissue burns. In this study, we developed a new type of nanoparticle, F68-PKI@PCN224, aims to achieve effective PDT upon medullary thyroid carcinoma (MTC) which is an uncommon form of thyroid cancer that originates in the parafollicular cells of the thyroid and the therapeutic outlook for patients with MTC remains unsatisfactory. F68-PKI@PCN224 combines the antitumor features of PDT with mammalian target of rapamycin (mTOR) inhibitor PKI-587 (PKI). The tumor sensitization, slow release, and pH response features of F68-PKI@PCN224 was demonstrated by a series of in vitro and in vivo experiments / assays. F68-PKI@PCN224 achieved the long-term activation and slow releasing of PKI and TCPP in MTC tumor tissues. During the process of generating PDT effects, F68-PKI@PCN224 enhanced the tumor's sensitivity to PDT, direct laser irradiation of MTC cells or subcutaneous tumor tissues. As a result, low-dose phototherapy achieves a higher anti-tumor effect upon F68-PKI@PCN224 compared with TCPP. This study reveals the synergistic effect between tumor sensitization by mTOR inhibitor and PDT and initially unveils the mechanism of action of these nanoparticles.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457049","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}
引用次数: 0
Electroporation-derived melanoma extracellular particles activate fibroblasts 电穿孔衍生的黑色素瘤细胞外颗粒可激活成纤维细胞。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-10-18 DOI: 10.1016/j.bbagen.2024.130723
Anna Choromańska , Urszula Szwedowicz , Anna Szewczyk , Małgorzata Daczewska , Jolanta Saczko , Roksana Kruszakin , Krzysztof J. Pawlik , Dagmara Baczyńska , Julita Kulbacka
{"title":"Electroporation-derived melanoma extracellular particles activate fibroblasts","authors":"Anna Choromańska ,&nbsp;Urszula Szwedowicz ,&nbsp;Anna Szewczyk ,&nbsp;Małgorzata Daczewska ,&nbsp;Jolanta Saczko ,&nbsp;Roksana Kruszakin ,&nbsp;Krzysztof J. Pawlik ,&nbsp;Dagmara Baczyńska ,&nbsp;Julita Kulbacka","doi":"10.1016/j.bbagen.2024.130723","DOIUrl":"10.1016/j.bbagen.2024.130723","url":null,"abstract":"<div><div>Although the pulse electric field (PEF) has been used in electrochemotherapy (ECT) for many years, the kinetics and profile of extracellular particles (EPs) released as a result of reversible electroporation have yet to be studied. It also needs to be clarified whether and how the profile of released EPs depends on the parameters of the applied PEF. The presented studies investigated the effect of EPs released from human melanoma cells after various parameters of reversible electroporation on markers indicating EP-mediated transformation of normal fibroblasts into tumor-associated fibroblasts. The expression levels of the vascular cell adhesion molecule-1 (VCAM-1) and changes in the expression of phosphor-histone H3 (pHH3), a biomarker specific for cells in mitosis, cell viability, and the migration capacity of the studied fibroblast cells, were analyzed. EPs were isolated from two commercial malignant melanoma cell lines previously subjected to reversible electroporation. Human primary fibroblasts (HPFs) were selected for EPs exposure. It was observed that after incubation with melanoma-derived EPs, HPFs showed differences in cell viability, migration capacity, VCAM-1, pHH3, and N-cadherin expression, depending on PEF parameters and the grade of melanoma cells. This study highlights that small extracellular particles (sEPs) from cancer cells can promote metastasis by carrying specific signals that lead to the upregulation of molecules like FAK, MMP-9, and N-cadherin in recipient cells.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457050","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}
引用次数: 0
Personalized biocorona as disease biomarker: The challenges and opportunities 作为疾病生物标志物的个性化生物传感器:挑战与机遇。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-10-18 DOI: 10.1016/j.bbagen.2024.130724
Mahtab Jahanshah Talab , Ali Valizadeh , Zahra Tahershamsi , Mohammad Reza Housaindokht , Bijan Ranjbar
{"title":"Personalized biocorona as disease biomarker: The challenges and opportunities","authors":"Mahtab Jahanshah Talab ,&nbsp;Ali Valizadeh ,&nbsp;Zahra Tahershamsi ,&nbsp;Mohammad Reza Housaindokht ,&nbsp;Bijan Ranjbar","doi":"10.1016/j.bbagen.2024.130724","DOIUrl":"10.1016/j.bbagen.2024.130724","url":null,"abstract":"<div><div>It is well known that when nanoparticles interact with biological fluids, a layer of proteins and biological components forms on them. This layer may alter the biological fate and efficiency of the nanomaterial. Recent studies have shown that illness states have a major impact on the structure of the biocorona, sometimes referred to as the “personalized protein corona.” Physiological factors like illness, which impact the proteome and metabolome pattern and result in conformational changes in proteins, give rise to this structure of discrimination in biocorona decoration. Improving the efficiency of precise platforms for developing new molecular biomarkers for accurate illness diagnosis is vitally necessary. The biocorona pattern's discrimination may be a diagnostic tool for designing biosensors. As a result, in this review, we summarize the most current studies on the relationship between physiological conditions and the variety of biocorona patterns that influence the biological responses of nanosystems. The biocorona pattern's flexibility may provide new research directions and be utilized to create nanoparticle-based therapeutic and diagnostic products suited to certain physiological situations.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457048","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}
引用次数: 0
VotePLMs-AFP: Identification of antifreeze proteins using transformer-embedding features and ensemble learning VotePLMs-AFP:利用变压器嵌入特征和集合学习识别抗冻蛋白
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-10-18 DOI: 10.1016/j.bbagen.2024.130721
Dawei Qi, Taigang Liu
{"title":"VotePLMs-AFP: Identification of antifreeze proteins using transformer-embedding features and ensemble learning","authors":"Dawei Qi,&nbsp;Taigang Liu","doi":"10.1016/j.bbagen.2024.130721","DOIUrl":"10.1016/j.bbagen.2024.130721","url":null,"abstract":"<div><div>Antifreeze proteins (AFPs) are a unique class of biomolecules capable of protecting other proteins, cell membranes, and cellular structures within organisms from damage caused by freezing conditions. Given the significance of AFPs in various domains such as biotechnology, agriculture, and medicine, several machine learning methods have been developed to identify AFPs. However, due to the complexity and diversity of AFPs, the predictive performance of existing methods is limited. Therefore, there is an urgent need to develop an efficient and rapid computational method for accurately predicting AFPs. In this study, we proposed a novel predictor based on transformer-embedding features and ensemble learning for the identification of AFPs, termed VotePLMs-AFP. Firstly, three types of feature descriptors were extracted from pre-trained protein language models (PLMs) during the feature extraction process. Subsequently, we analyzed six combinations generated by these three embeddings to explore the optimal feature set, which was input into the soft voting-based ensemble learning classifier for the identification of AFPs. Finally, we evaluated the model on the two benchmark datasets. The experimental results show that our model achieves high prediction accuracy in 10-fold cross-validation (CV) and independent set testing, outperforming existing state-of-the-art methods. Therefore, our model could serve as an effective tool for predicting AFPs.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457051","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}
引用次数: 0
FAHFA promotes intracellular calcium signaling via activating the fat taste receptor, CD36 and Src protein kinases in mice taste bud cells FAHFA 通过激活小鼠味蕾细胞中的脂肪味觉受体、CD36 和 Src 蛋白激酶促进细胞内钙信号转导。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-10-18 DOI: 10.1016/j.bbagen.2024.130722
Karthi Muthuswamy , Keerthana Vasanthakumar , Prabha Panneerselvan , Lokesh Thangamani , Vasanth Krishnan , Shanmughavel Piramanayagam , Selvakumar Subramaniam
{"title":"FAHFA promotes intracellular calcium signaling via activating the fat taste receptor, CD36 and Src protein kinases in mice taste bud cells","authors":"Karthi Muthuswamy ,&nbsp;Keerthana Vasanthakumar ,&nbsp;Prabha Panneerselvan ,&nbsp;Lokesh Thangamani ,&nbsp;Vasanth Krishnan ,&nbsp;Shanmughavel Piramanayagam ,&nbsp;Selvakumar Subramaniam","doi":"10.1016/j.bbagen.2024.130722","DOIUrl":"10.1016/j.bbagen.2024.130722","url":null,"abstract":"<div><div>Two lipid sensors, CD36 and GPR120, are crucial for the orosensory detection of fat taste and for mediating fat preference. However, the mechanism by which endogenous lipid (FAHFA) binds to CD36 to initiate intracellular signaling remains unexplained. Hence, the primary objective of this study is to investigate the binding mechanism of FAHFA to CD36 and its role in isolated mouse taste bud cells (mTBCs). The Schrodinger platform was used to assess the molecular dynamics of protein and ligand interactions, and an <em>in vitro</em> experiment was used to validate the findings. Based on the docking score of the ligand, the molecular mechanistic activities of the targeted complexes, CD36–5-POHSA (−8.2 kcal/mol), were investigated using the dynamic simulation. In comparison to linoleic acid (LA), POHSA rapidly increased [Ca<sup>2+</sup>]i <em>via</em> acting on CD36, and 5-POHSA treatment in mTBCs activated src-kinase at 20 μM. CD36 siRNA transfection in TBCs downregulate the CD36 protein expression as well as [Ca<sup>2+</sup>]i flux. This study suggests that 5-POHSA may help combat taste abnormalities and the adverse effects of obesity by binding to the lingual CD36 receptor and activating the tongue-brain axis.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457047","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}
引用次数: 0
Supplementation with ions enhances the efficiency of nucleic acid delivery with cell-penetrating peptides 补充离子可提高细胞穿透肽递送核酸的效率。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-10-05 DOI: 10.1016/j.bbagen.2024.130719
İrem Ilgın Gümüşoğlu , Maria Maloverjan , Ly Porosk, Margus Pooga
{"title":"Supplementation with ions enhances the efficiency of nucleic acid delivery with cell-penetrating peptides","authors":"İrem Ilgın Gümüşoğlu ,&nbsp;Maria Maloverjan ,&nbsp;Ly Porosk,&nbsp;Margus Pooga","doi":"10.1016/j.bbagen.2024.130719","DOIUrl":"10.1016/j.bbagen.2024.130719","url":null,"abstract":"<div><div>The successful delivery of therapeutic nucleic acids (NAs) into eukaryotic cells is essential for numerous biomedical applications, including gene therapy, gene silencing, and genome editing. Cell-penetrating peptides (CPPs) have claimed significant attention as delivery vehicles due to their inherent ability to penetrate cellular membranes and efficiently transport cargo, including NAs, into the cells. However, further optimization and a deeper understanding of underlying mechanisms are necessary for such transfection methods. Previous studies have demonstrated that Ca<sup>2+</sup> ions can significantly enhance NA delivery efficiency when included in transfection media or CPP/NA nanoparticles during preparation. Similar effects have been observed for Mg<sup>2+</sup>, but the impact of other ions in this context has not been thoroughly investigated. In this study, we supplemented the CPP/NA formulations with various inorganic biocompatible ions by introducing solutions of the respective salts to colloidal nanoparticles at the preparation stage. Our results indicated that supplementing the CPP/NA formulations with certain salt solutions enhanced the biological effect achieved with NAs while also influencing nanoparticle size, surface charge, complexation stability, and, to some extent, the internalization route. Our findings offer valuable insights for optimizing the formation of CPP nanoparticles to improve NA delivery efficiency.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380022","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}
引用次数: 0
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