Biomolecular Concepts最新文献_第3页

Potential PDE4B inhibitors as promising candidates against SARS-CoV-2 infection. 潜在的PDE4B抑制剂是对抗严重急性呼吸系统综合征冠状病毒2型感染的有前景的候选者。

Biomolecular Concepts Pub Date : 2023-11-01 eCollection Date: 2023-01-01 DOI: 10.1515/bmc-2022-0033

Federica Giuzio, Maria Grazia Bonomo, Alessia Catalano, Vittoria Infantino, Giovanni Salzano, Magnus Monné, Athina Geronikaki, Anthi Petrou, Stefano Aquaro, Maria Stefania Sinicropi, Carmela Saturnino

{"title":"Potential PDE4B inhibitors as promising candidates against SARS-CoV-2 infection.","authors":"Federica Giuzio, Maria Grazia Bonomo, Alessia Catalano, Vittoria Infantino, Giovanni Salzano, Magnus Monné, Athina Geronikaki, Anthi Petrou, Stefano Aquaro, Maria Stefania Sinicropi, Carmela Saturnino","doi":"10.1515/bmc-2022-0033","DOIUrl":"10.1515/bmc-2022-0033","url":null,"abstract":"Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an RNA virus belonging to the coronavirus family responsible for coronavirus disease 2019 (COVID-19). It primarily affects the pulmonary system, which is the target of chronic obstructive pulmonary disease (COPD), for which many new compounds have been developed. In this study, phosphodiesterase 4 (PDE4) inhibitors are being investigated. The inhibition of PDE4 enzyme produces anti-inflammatory and bronchodilator effects in the lung by inducing an increase in cAMP concentrations. Piclamilast and rolipram are known selective inhibitors of PDE4, which are unfortunately endowed with common side effects, such as nausea and emesis. The selective inhibition of the phosphodiesterase 4B (PDE4B) subtype may represent an intriguing technique for combating this highly contagious disease with fewer side effects. In this article, molecular docking studies for the selective inhibition of the PDE4B enzyme have been carried out on 21 in-house compounds. The compounds were docked into the pocket of the PDE4B catalytic site, and in most cases, they were almost completely superimposed onto piclamilast. Then, in order to enlarge our study, drug-likeness prediction studies were performed on the compounds under study.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427582","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}

引用次数: 0

Proteins turn "Proteans" - The over 40-year delayed paradigm shift in structural biology: From "native proteins in uniquely defined configurations" to "intrinsically disordered proteins". 蛋白质转变为“变形体”-结构生物学中超过40年的延迟范式转变:从“独特定义结构的天然蛋白质”到“内在无序的蛋白质”。

Biomolecular Concepts Pub Date : 2023-01-01 DOI: 10.1515/bmc-2022-0030

Eugenio Frixione, Lourdes Ruiz-Zamarripa

引用次数: 0

Modeling of olfactory transduction in AWC^ON neuron via coupled electrical-calcium dynamics. 基于电-钙耦合动力学的AWCON神经元嗅觉转导模型。

Biomolecular Concepts Pub Date : 2023-01-01 DOI: 10.1515/bmc-2022-0035

Martina Nicoletti, Nicole Luchetti, Letizia Chiodo, Alessandro Loppini, Viola Folli, Giancarlo Ruocco, Simonetta Filippi

{"title":"Modeling of olfactory transduction in AWCON neuron via coupled electrical-calcium dynamics.","authors":"Martina Nicoletti, Nicole Luchetti, Letizia Chiodo, Alessandro Loppini, Viola Folli, Giancarlo Ruocco, Simonetta Filippi","doi":"10.1515/bmc-2022-0035","DOIUrl":"https://doi.org/10.1515/bmc-2022-0035","url":null,"abstract":"Amphid wing \"C\" (AWC) neurons are among the most important and studied neurons of the nematode Caenorhabditis elegans. In this work, we unify the existing electrical and intracellular calcium dynamics descriptions to obtain a biophysically accurate model of olfactory transduction in AWCON neurons. We study the membrane voltage and the intracellular calcium dynamics at different exposure times and odorant concentrations to grasp a complete picture of AWCON functioning. Moreover, we investigate the complex cascade of biochemical processes that allow AWC activation upon odor removal. We analyze the behavior of the different components of the models and, by suppressing them selectively, we extrapolate their contribution to the overall neuron response and study the resilience of the dynamical system. Our results are all in agreement with the available experimental data. Therefore, we provide an accurate mathematical and biophysical model for studying olfactory signal processing in C. elegans.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9988910","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}

引用次数: 0

Head or tail? A molecular dynamics approach to the complex structure of TNF-associated factor TRAF2. 头还是尾?tnf相关因子TRAF2复杂结构的分子动力学研究。

Biomolecular Concepts Pub Date : 2023-01-01 DOI: 10.1515/bmc-2022-0031

Fulvio Erba, Luisa Di Paola, Almerinda Di Venere, Eloise Mastrangelo, Federica Cossu, Giampiero Mei, Velia Minicozzi

{"title":"Head or tail? A molecular dynamics approach to the complex structure of TNF-associated factor TRAF2.","authors":"Fulvio Erba, Luisa Di Paola, Almerinda Di Venere, Eloise Mastrangelo, Federica Cossu, Giampiero Mei, Velia Minicozzi","doi":"10.1515/bmc-2022-0031","DOIUrl":"https://doi.org/10.1515/bmc-2022-0031","url":null,"abstract":"Tumor necrosis factor receptor-associated factor proteins (TRAFs) are trimeric proteins that play a fundamental role in signaling, acting as intermediaries between the tumor necrosis factor (TNF) receptors and the proteins that transmit the downstream signal. The monomeric subunits of all the TRAF family members share a common tridimensional structure: a C-terminal globular domain and a long coiled-coil tail characterizing the N-terminal section. In this study, the dependence of the TRAF2 dynamics on the length of its tail was analyzed in silico. In particular, we used the available crystallographic structure of a C-terminal fragment of TRAF2 (168 out of 501 a.a.), TRAF2-C, and that of a longer construct, addressed as TRAF2-plus, that we have re-constructed using the AlphaFold2 code. The results indicate that the longer N-terminal tail of TRAF2-plus has a strong influence on the dynamics of the globular regions in the protein C-terminal head. In fact, the quaternary interactions among the TRAF2-C subunits change asymmetrically in time, while the movements of TRAF2-plus monomers are rather limited and more ordered than those of the shorter construct. Such findings shed a new light on the dynamics of TRAF subunits and on the protein mechanism in vivo, since TRAF monomer-trimer equilibrium is crucial for several reasons (receptor recognition, membrane binding, hetero-oligomerization).","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9751670","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}

引用次数: 0

A commentary on the inhibition of human TPC2 channel by the natural flavonoid naringenin: Methods, experiments, and ideas. 天然类黄酮柚皮素抑制人TPC2通道的研究进展:方法、实验与思路。

Biomolecular Concepts Pub Date : 2023-01-01 DOI: 10.1515/bmc-2022-0036

Velia Minicozzi, Tianwen Qi, Antonella Gradogna, Marina Pozzolini, Stefan Milenkovic, Antonio Filippini, Matteo Ceccarelli, Armando Carpaneto

引用次数: 0

Effects of model membranes on lysozyme amyloid aggregation. 模型膜对溶菌酶淀粉样蛋白聚集的影响。

Biomolecular Concepts Pub Date : 2023-01-01 DOI: 10.1515/bmc-2022-0034

Annaclaudia Burrelli, Paolo Moretti, Yuri Gerelli, Maria Grazia Ortore

{"title":"Effects of model membranes on lysozyme amyloid aggregation.","authors":"Annaclaudia Burrelli, Paolo Moretti, Yuri Gerelli, Maria Grazia Ortore","doi":"10.1515/bmc-2022-0034","DOIUrl":"https://doi.org/10.1515/bmc-2022-0034","url":null,"abstract":"The study of the interaction between lipid membranes and amyloidogenic peptides is a turning point for understanding the processes involving the cytotoxicity of peptides involved in neurodegenerative diseases. In this work, we perform an experimental study of model membrane-lysozyme interaction to understand how the formation of amyloid fibrils can be affected by the presence of polar and zwitterionic phospholipid molecules (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine [POPC] and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol [POPG]). The study was conducted above and below the critical micellar concentration (CMC) using dynamic light scattering (DLS), atomic force microscopy (AFM), UV-Vis spectrophotometry, and the quartz crystal microbalance (QCM). Our results show that the presence of phospholipids appears to be a factor favoring the formation of amyloid aggregates. Spectrophotometric and DLS data revealed that the quantity of <math><mi>β</mi></math> -structure increases in the presence of POPG and POPC at different concentrations. The presence of POPG and POPC increases the speed of the nucleation process, without altering the overall structures of the fibrillar final products.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9946293","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}

引用次数: 0

Setting up multicolour TIRF microscopy down to the single molecule level. 设置多色TIRF显微镜到单分子水平。

Biomolecular Concepts Pub Date : 2023-01-01 DOI: 10.1515/bmc-2022-0032

Chiara Schirripa Spagnolo, Stefano Luin

{"title":"Setting up multicolour TIRF microscopy down to the single molecule level.","authors":"Chiara Schirripa Spagnolo, Stefano Luin","doi":"10.1515/bmc-2022-0032","DOIUrl":"https://doi.org/10.1515/bmc-2022-0032","url":null,"abstract":"Investigating biological mechanisms in ever greater detail requires continuous advances in microscopy techniques and setups. Total internal reflection fluorescence (TIRF) microscopy is a well-established technique for visualizing processes on the cell membrane. TIRF allows studies down to the single molecule level, mainly in single-colour applications. Instead, multicolour setups are still limited. Here, we describe our strategies for implementing a multi-channel TIRF microscopy system capable of simultaneous two-channel excitation and detection, starting from a single-colour commercial setup. First, we report some applications at high molecule density and then focus on the challenges we faced for achieving the single molecule level simultaneously in different channels, showing that rigorous optimizations on the setup are needed to increase its sensitivity up to this point, from camera setting to background minimization. We also discuss our strategies regarding crucial points of fluorescent labelling for this type of experiment: labelling strategy, kind of probe, efficiency, and orthogonality of the reaction, all of which are aspects that can influence the achievable results. This work may provide useful guidelines for setting up advanced single-molecule multi-channel TIRF experiments to obtain insights into interaction mechanisms on the cell membrane of living cells.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9813081","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}

引用次数: 1

Dipalmitoyl-phosphatidylserine-filled cationic maltodextrin nanoparticles exhibit enhanced efficacy for cell entry and intracellular protein delivery in phagocytic THP-1 cells. 双棕榈酰磷脂酰丝氨酸填充的阳离子麦芽糖糊精纳米颗粒在吞噬THP-1细胞中表现出增强的细胞进入和细胞内蛋白质递送的功效。

Biomolecular Concepts Pub Date : 2023-01-01 DOI: 10.1515/bmc-2022-0029

Clément Brinkhuizen, Damien Shapman, Alexis Lebon, Magalie Bénard, Meryem Tardivel, Laurent Dubuquoy, Ludovic Galas, Rodolphe Carpentier

{"title":"Dipalmitoyl-phosphatidylserine-filled cationic maltodextrin nanoparticles exhibit enhanced efficacy for cell entry and intracellular protein delivery in phagocytic THP-1 cells.","authors":"Clément Brinkhuizen, Damien Shapman, Alexis Lebon, Magalie Bénard, Meryem Tardivel, Laurent Dubuquoy, Ludovic Galas, Rodolphe Carpentier","doi":"10.1515/bmc-2022-0029","DOIUrl":"https://doi.org/10.1515/bmc-2022-0029","url":null,"abstract":"Vaccination through the upper respiratory tract is a promising strategy, and particulate antigens, such as antigens associated with nanoparticles, triggered a stronger immune response than the sole antigens. Cationic maltodextrin-based nanoparticles loaded with phosphatidylglycerol (NPPG) are efficient for intranasal vaccination but non-specific to trigger immune cells. Here we focused on phosphatidylserine (PS) receptors, specifically expressed by immune cells including macrophages, to improve nanoparticle targeting through an efferocytosis-like mechanism. Consequently, the lipids associated with NPPG have been substituted by PS to generate cationic maltodextrin-based nanoparticles with dipalmitoyl-phosphatidylserine (NPPS). Both NPPS and NPPG exhibited similar physical characteristics and intracellular distribution in THP-1 macrophages. NPPS cell entry was faster and higher (two times more) than NPPG. Surprisingly, competition of PS receptors with phospho-L-serine did not alter NPPS cell entry and annexin V did not preferentially interact with NPPS. Although the protein association is similar, NPPS delivered more proteins than NPPG in cells. On the contrary, the proportion of mobile nanoparticles (50%), the movement speed of nanoparticles (3 µm/5 min), and protein degradation kinetics in THP-1 were not affected by lipid substitution. Together, the results indicate that NPPS enter cells and deliver protein better than NPPG, suggesting that modification of the lipids of cationic maltodextrin-based nanoparticles may be a useful strategy to enhance nanoparticle efficacy for mucosal vaccination.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9686476","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}

引用次数: 0

The effects of supplementation of Nannochloropsis oculata microalgae on biochemical, inflammatory and antioxidant responses in diabetic rats. 补充纳米绿藻对糖尿病大鼠生化、炎症和抗氧化反应的影响。

Biomolecular Concepts Pub Date : 2022-10-31 eCollection Date: 2022-01-01 DOI: 10.1515/bmc-2022-0025

Ali Fereidouni, Ali Khaleghian, Neda Mousavi-Niri, Nasrollah Moradikor

{"title":"The effects of supplementation of Nannochloropsis oculata microalgae on biochemical, inflammatory and antioxidant responses in diabetic rats.","authors":"Ali Fereidouni, Ali Khaleghian, Neda Mousavi-Niri, Nasrollah Moradikor","doi":"10.1515/bmc-2022-0025","DOIUrl":"https://doi.org/10.1515/bmc-2022-0025","url":null,"abstract":"Diabetes is accompanied by inflammation and oxidation. Supplementation of anti-inflammatory and antioxidant compounds can prevent the progression of diabetes. This study aimed to investigate the effects of supplementation of Nannochloropsis oculata microalgae (NOM) on the inflammatory and antioxidant responses in diabetic rats. Sixty male rats were divided into six groups as diabetic and non-diabetic rats receiving 0, 10 and 20 mg/kg of body weight of NOM daily for 21 days. Body weight, the serum concentrations of insulin and glucose and the tissue concentrations of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), malondialdehyde (MDA), ferric reducing antioxidant power (FRAP), superoxide dismutase (SOD), glutathione peroxidase (GPx) were assessed. The results showed that induction of diabetes significantly reduced the body weight, the serum concentrations of insulin and the tissue concentrations of SOD, FRAP and GPx while increasing the concentrations of glucose, MDA, IL-1β, IL-6, NF-κB and TNF-α. Daily oral administration of NOM (10 and 20 mg/kg) significantly maintained the body weight, the serum concentrations of insulin and the tissue concentrations of SOD, FRAP and GPx while preventing the increase in the concentrations of glucose, MDA, IL-1β and TNF-α. In conclusion, diabetes caused inflammation and oxidation while NOM worked as a natural anti-inflammatory and antioxidant compound.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"314-321"},"PeriodicalIF":0.0,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40657886","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}

引用次数: 2

Insights into functional connectivity in mammalian signal transduction pathways by pairwise comparison of protein interaction partners of critical signaling hubs. 通过对关键信号中枢蛋白相互作用伙伴的两两比较，深入了解哺乳动物信号转导途径的功能连接。

Biomolecular Concepts Pub Date : 2022-09-01 eCollection Date: 2022-01-01 DOI: 10.1515/bmc-2022-0023

Chilakamarti V Ramana

{"title":"Insights into functional connectivity in mammalian signal transduction pathways by pairwise comparison of protein interaction partners of critical signaling hubs.","authors":"Chilakamarti V Ramana","doi":"10.1515/bmc-2022-0023","DOIUrl":"https://doi.org/10.1515/bmc-2022-0023","url":null,"abstract":"Growth factors and cytokines activate signal transduction pathways and regulate gene expression in eukaryotes. Intracellular domains of activated receptors recruit several protein kinases as well as transcription factors that serve as platforms or hubs for the assembly of multi-protein complexes. The signaling hubs involved in a related biologic function often share common interaction proteins and target genes. This functional connectivity suggests that a pairwise comparison of protein interaction partners of signaling hubs and network analysis of common partners and their expression analysis might lead to the identification of critical nodes in cellular signaling. A pairwise comparison of signaling hubs across several related pathways might reveal novel signaling modules. Analysis of protein interaction connectome by Venn (PIC-Venn) of transcription factors STAT1, STAT3, NFKB1, RELA, FOS, and JUN, and their common interaction network suggested that BRCA1 and TSC22D3 function as critical nodes in immune responses by connecting the signaling hubs into signaling modules. Transcriptional regulation of critical hubs may play a major role in the lung epithelial cells in response to SARS-CoV-2 and in COVID-19 patients. Mutations and differential expression levels of these critical nodes and modules in pathological conditions might deregulate signaling pathways and their target genes involved in inflammation. Biological connectivity emerges from the structural connectivity of interaction networks across several signaling hubs in related pathways. The main objectives of this study are to identify critical hubs, critical nodes, and modules involved in the signal transduction pathways of innate and adaptive immunity. Application of PIC-Venn to several signaling hubs might reveal novel nodes and modules that can be targeted by small regulatory molecules to simultaneously activate or inhibit cell signaling in health and disease.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"298-313"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40336732","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}

引用次数: 0