S. Bruno, Marilena Margiotta, Marco Cozzolino, P. Bianchini, A. Diaspro, L. Cavanna, M. Tognolini, S. Abbruzzetti, C. Viappiani
{"title":"A photosensitizing fusion protein with targeting capabilities","authors":"S. Bruno, Marilena Margiotta, Marco Cozzolino, P. Bianchini, A. Diaspro, L. Cavanna, M. Tognolini, S. Abbruzzetti, C. Viappiani","doi":"10.1515/bmc-2022-0014","DOIUrl":"https://doi.org/10.1515/bmc-2022-0014","url":null,"abstract":"Abstract The photodynamic treatment for antimicrobial applications or anticancer therapy relies on reactive oxygen species generated by photosensitizing molecules after absorption of visible or near-infrared light. If the photosensitizing molecule is in close vicinity of the microorganism or the malignant cell, a photocytotoxic action is exerted. Therefore, the effectiveness of photosensitizing compounds strongly depends on their capability to target microbial or cancer-specific proteins. In this study, we report on the preparation and preliminary characterization of human recombinant myoglobin fused to the vasoactive intestinal peptide to target vasoactive intestinal peptide receptor (VPAC) receptors. Fe-protoporphyrin IX was replaced by the photosensitizing compound Zn-protoporphyrin IX. Taking advantage of the fluorescence emission by Zn-protoporphyrin IX, we show that the construct can bind prostate cancer cells where the VPAC receptors are expressed.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"175 - 182"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49139331","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":"Diffusion of molecules through nanopores under confinement: Time-scale bridging and crowding effects via Markov state model","authors":"I. Bodrenko, S. Milenkovic, M. Ceccarelli","doi":"10.1515/bmc-2022-0019","DOIUrl":"https://doi.org/10.1515/bmc-2022-0019","url":null,"abstract":"Abstract Passive transport of molecules through nanopores is characterized by the interaction of molecules with pore internal walls and by a general crowding effect due to the constricted size of the nanopore itself, which limits the presence of molecules in its interior. The molecule–pore interaction is treated within the diffusion approximation by introducing the potential of mean force and the local diffusion coefficient for a correct statistical description. The crowding effect can be handled within the Markov state model approximation. By combining the two methods, one can deal with complex free energy surfaces taking into account crowding effects. We recapitulate the equations bridging the two models to calculate passive currents assuming a limited occupancy of the nanopore in a wide range of molecular concentrations. Several simple models are analyzed to clarify the consequences of the model. Eventually, a biologically relevant case of transport of an antibiotic molecule through a bacterial porin is used to draw conclusions (i) on the effects of crowding on transport of small molecules through biological channels, and (ii) to demonstrate its importance for modelling of cellular transport.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"207 - 219"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48543533","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}
E. De Santis, V. Minicozzi, G. Rossi, F. Stellato, S. Morante
{"title":"Is styrene competitive for dopamine receptor binding?","authors":"E. De Santis, V. Minicozzi, G. Rossi, F. Stellato, S. Morante","doi":"10.1515/bmc-2022-0016","DOIUrl":"https://doi.org/10.1515/bmc-2022-0016","url":null,"abstract":"Abstract The potential role of styrene oxide in altering the dopaminergic pathway in the ear is investigated by means of molecular docking and molecular dynamics simulations. We estimate the binding affinity of both styrene oxide and dopamine to the dopaminergic receptor DrD2 by computing the free-energy difference, ∆G, between the configuration where the ligand is bound to the receptor and the situation in which it is “infinitely” far away from it. The results show that the styrene oxide has a somewhat lower affinity for binding with respect to dopamine, which, however, may not be enough to prevent exogenous high concentration styrene oxide to compete with endogenous dopamine for DrD2 binding.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"200 - 206"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43572865","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}
Vladimir A. Martínez-Rojas, L. J. Juárez-Hernández, C. Musio
{"title":"Ion channels and neuronal excitability in polyglutamine neurodegenerative diseases","authors":"Vladimir A. Martínez-Rojas, L. J. Juárez-Hernández, C. Musio","doi":"10.1515/bmc-2022-0018","DOIUrl":"https://doi.org/10.1515/bmc-2022-0018","url":null,"abstract":"Abstract Polyglutamine (polyQ) diseases are a family composed of nine neurodegenerative inherited disorders (NDDs) caused by pathological expansions of cytosine-adenine-guanine (CAG) trinucleotide repeats which encode a polyQ tract in the corresponding proteins. CAG polyQ repeat expansions produce neurodegeneration via multiple downstream mechanisms; among those the neuronal activity underlying the ion channels is affected directly by specific channelopathies or indirectly by secondary dysregulation. In both cases, the altered excitability underlies to gain- or loss-of-function pathological effects. Here we summarize the repertoire of ion channels in polyQ NDDs emphasizing the biophysical features of neuronal excitability and their pathogenic role. The aim of this review is to point out the value of a deeper understanding of those functional mechanisms and processes as crucial elements for the designing and targeting of novel therapeutic avenues.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"183 - 199"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46331796","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}
Beatrice Senigagliesi, Diana E Bedolla, Giovanni Birarda, Michele Zanetti, Marco Lazzarino, Lisa Vaccari, Pietro Parisse, Loredana Casalis
{"title":"Subcellular elements responsive to the biomechanical activity of triple-negative breast cancer-derived small extracellular vesicles.","authors":"Beatrice Senigagliesi, Diana E Bedolla, Giovanni Birarda, Michele Zanetti, Marco Lazzarino, Lisa Vaccari, Pietro Parisse, Loredana Casalis","doi":"10.1515/bmc-2022-0024","DOIUrl":"https://doi.org/10.1515/bmc-2022-0024","url":null,"abstract":"Abstract Triple-negative breast cancer (TNBC) stands out for its aggressive, fast spread, and highly metastatic behavior and for being unresponsive to the classical hormonal therapy. It is considered a disease with a poor prognosis and limited treatment options. Among the mechanisms that contribute to TNBC spreading, attention has been recently paid to small extracellular vesicles (sEVs), nano-sized vesicles that by transferring bioactive molecules to recipient cells play a crucial role in the intercellular communication among cancer, healthy cells, and tumor microenvironment. In particular, TNBC-derived sEVs have been shown to alter proliferation, metastasis, drug resistance, and biomechanical properties of target cells. To shed light on the molecular mechanisms involved in sEVs mediation of cell biomechanics, we investigated the effects of sEVs on the main subcellular players, i.e., cell membrane, cytoskeleton, and nuclear chromatin organization. Our results unveiled that TNBC-derived sEVs are able to promote the formation and elongation of cellular protrusions, soften the cell body, and induce chromatin decondensation in recipient cells. In particular, our data suggest that chromatin decondensation is the main cause of the global cell softening. The present study added new details and unveiled a novel mechanism of activity of the TNBC-derived sEVs, providing information for the efficient translation of sEVs to cancer theranostics.","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"13 1","pages":"322-333"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10406657","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}
José Manuel Pérez de la Lastra, Victoria Baca-González, Sergio González-Acosta, Patricia Asensio-Calavia, Andrea Otazo-Pérez, Antonio Morales-delaNuez
{"title":"Antibodies targeting enzyme inhibition as potential tools for research and drug development.","authors":"José Manuel Pérez de la Lastra, Victoria Baca-González, Sergio González-Acosta, Patricia Asensio-Calavia, Andrea Otazo-Pérez, Antonio Morales-delaNuez","doi":"10.1515/bmc-2021-0021","DOIUrl":"https://doi.org/10.1515/bmc-2021-0021","url":null,"abstract":"<p><p>Antibodies have transformed biomedical research and are now being used for different experimental applications. Generally, the interaction of enzymes with their specific antibodies can lead to a reduction in their enzymatic activity. The effect of the antibody is dependent on its narrow i.e. the regions of the enzyme to which it is directed. The mechanism of this inhibition is rarely a direct combination of the antibodies with the catalytic site, but is rather due to steric hindrance, barring the substrate access to the active site. In several systems, however, the interaction with the antibody induces conformational changes on the enzyme that can either inhibit or enhance its catalytic activity. The extent of enzyme inhibition or enhancement is, therefore, a reflection of the nature and distribution of the various antigenic determinants on the enzyme molecule. Currently, the mode of action of many enzymes has been elucidated at the molecular level. We here review the molecular mechanisms and recent trends by which antibodies inhibit the catalytic activity of enzymes and provide examples of how specific antibodies can be useful for the neutralization of biologically active molecules.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"215-232"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39878139","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}
Mostafa Mohamed El-Sersawy, Saad El-Din Hassan, Abbas A El-Ghamry, Amr Mahmoud Abd El-Gwad, Amr Fouda
{"title":"Implication of plant growth-promoting rhizobacteria of <i>Bacillus</i> spp. as biocontrol agents against wilt disease caused by <i>Fusarium oxysporum</i> Schlecht. in <i>Vicia faba</i> L.","authors":"Mostafa Mohamed El-Sersawy, Saad El-Din Hassan, Abbas A El-Ghamry, Amr Mahmoud Abd El-Gwad, Amr Fouda","doi":"10.1515/bmc-2021-0020","DOIUrl":"https://doi.org/10.1515/bmc-2021-0020","url":null,"abstract":"<p><p>Out of seven <i>Fusarium</i> spp. isolated from infected faba bean roots, two <i>Fusarium oxysporum</i> were selected and showed faba bean-wilt disease severity with percentages of 68% and 47% under greenhouse conditions. The <i>F. oxysporum</i> showed the highest wilt disease was selected to complete the current study. Three rhizobacterial strains were isolated and identified as <i>Bacillus velezensis</i> Vb1, <i>B. paramycoides</i> Vb3, and <i>B. paramycoides</i> Vb6. These strains showed the highest <i>in-vitro</i> antagonistic activity by the dual-culture method against selected <i>F. oxysporum</i> with inhibition percentages of 59±0.2, 46±0.3, and 52±0.3% for Vb1, Vb3, and Vb6, respectively. These rhizobacterial strains exhibit varied activity for nitrogen-fixing and phosphate-solubilizing. Moreover, these strains showed positive results for ammonia, HCN, and siderophores production. The phytohormones production (indole-3-acetic acid, ABA, benzyl, kinten, ziaten, and GA<sub>3</sub>) and secretion of various lytic enzymes were recorded by these strains with varying degrees. Under greenhouse conditions, the rhizobacterial strains Vb1, Vb3, Vb6, and their consortium can protect faba bean from wilt caused by <i>F. oxysporum</i> with percentages of 70, 60, 65, and 82%, respectively. Under field conditions, the inoculation with the rhizobacterial consortium (Vb1+Vb3+Vb6) significantly increases the growth performance of the <i>F. oxysporum</i>-infected faba bean plant and recorded the highest wilt protection (83.3%).</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"197-214"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39830718","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":"Primary Erlotinib Resistance in a Patient with Non-Small Cell Lung Cancer Carrying Simultaneous Compound EGFR L718A, Q849H, and L858R Mutations.","authors":"Hanifeh Mirtavoos-Mahyari, Elham Rismani, Alireza Sarkar Lotfabadi, Azizollah Abbasi Dezfouli, Kambiz Sheikhy, Mojtaba Mokhber Dezfuli, Jalal Heshmatnia","doi":"10.1515/bmc-2021-0018","DOIUrl":"https://doi.org/10.1515/bmc-2021-0018","url":null,"abstract":"<p><p>Nowadays, mutations in the epidermal growth factor receptor (EGFR) kinase domain are studied in targeted therapy of non-small cell lung cancer (NSCLC) with EGFR tyrosine kinase inhibitors including gefitinib and erlotinib. The present study reports a rare case of a patient harboring three simultaneous EGFR mutations (L718A, Q849H, and L858R). The development of erlotinib resistance was detected in the subsequent treatment. Using a computational approach, the current study investigated the conformational changes of wild-type and mutant EGFR's kinase domains in the interaction with erlotinib. Their binding modes with erlotinib were elucidated during molecular dynamics simulation, where higher fluctuations were detected in the mutated forms of the EGFR tyrosine kinase domain. Prediction of stability and functional effect of mutations revealed that amino acidic substitutions have decreased the protein stability as well as the binding affinity to erlotinib. These results may be useful for a recommendation of EGFR mutational analysis for patients with NSCLC carcinoma.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"164-174"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39924667","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}
Mahmoud Soliman Abdel-Hamid, Amr Fouda, Hesham Kamal Abo El-Ela, Abbas A El-Ghamry, Saad El-Din Hassan
{"title":"Plant growth-promoting properties of bacterial endophytes isolated from roots of <i>Thymus vulgaris</i> L. and investigate their role as biofertilizers to enhance the essential oil contents.","authors":"Mahmoud Soliman Abdel-Hamid, Amr Fouda, Hesham Kamal Abo El-Ela, Abbas A El-Ghamry, Saad El-Din Hassan","doi":"10.1515/bmc-2021-0019","DOIUrl":"https://doi.org/10.1515/bmc-2021-0019","url":null,"abstract":"<p><p>The main objective of the current study was to improve the essential oil contents of <i>Thymus vulgaris</i> L. using bio-inoculation with bacterial endophytes. Therefore, out of fourteen endophytic bacterial isolates obtained from roots of <i>T. vulgaris</i>, five isolates were selected based on the highest nitrogen-fixation and phosphate solubilization activity and identified as: <i>Bacillus haynesii</i> T9r, <i>Citrobacter farmeri</i> T10r, <i>Bacillus licheniformis</i> T11r, <i>Bacillus velezensis</i> T12r, and <i>Bacillus velezensis</i> T13r. These five strains have been recorded as ammonia, hydrogen cyanide (HCN), siderophores, and indole-3-acetic acid (IAA) producers. These strains have the efficacy to fix-nitrogen by reduction of acetylene with values of 82.133±1.4-346.6±1.4 n-mole-C<sub>2</sub>H<sub>4</sub>/ml/24 h. The IAA, gibberellic acid, abscisic acid, benzyl, kinten, and ziaten production were confirmed using HPLC. Two strains of T11r and T13r showed the highest plant growth-promoting properties and were selected for bio-inoculation of <i>T. vulgaris</i> individually or in a consortium with different mineral fertilization doses (0, 50, 75, and 100%) under field conditions. The highest growth performance was attained with the endophytic consortium (T11r+T13r) in the presence of 100% mineral fertilization. The GC-MS analysis of thyme oil contents showed the presence of 23 various compounds with varying percentages and the thymol fraction represented the highest percentages (39.1%) in the presence of the bacterial consortium.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"175-196"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39830719","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":"SIT1 transporter as a potential novel target in treatment of COVID-19.","authors":"Sabina Semiz","doi":"10.1515/bmc-2021-0017","DOIUrl":"https://doi.org/10.1515/bmc-2021-0017","url":null,"abstract":"<p><p>Studies published earlier this year demonstrated the association of the solute carrier <i>SLC6A20</i> gene with the risk and severity of COVID-19. The <i>SLC6A20</i> protein product (Sodium-dependent Imino Transporter 1 (SIT1)) is involved in the transport of amino acids, including glycine. Here we summarized the results of recent studies demonstrating the interaction of SIT1 with the ACE2 receptor for SARS-CoV-2 as well as an observed association of <i>SLC6A20</i> with the risk and traits of Type 2 diabetes (T2D). Recently, it was also proposed that <i>SLC6A20</i> represents the novel regulator of glycine levels and that glycine has beneficial effects against the proinflammatory cytokine secretion induced by SARS-CoV-2 infection. Ivermectin, as a partial agonist of glycine-gated chloride channels, was also recently suggested to interfere with the COVID-19 cytokine storm by inducing the activation of glycine receptors. Furthermore, plasma glycine levels are found to be decreased in diabetic patients. Thus, further clinical trials are warranted to confirm the potential favorable effects of targeting the SIT1 transporter and glycine levels in the treatment of COVID-19, particularly for the severe case of disease associated with hyperglycemia, inflammation, and T2D. These findings suggest that SIT1 may potentially represent one of the missing pieces in the complex puzzle observed between these two pandemic diseases and the potential novel target for their efficient treatment.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"156-163"},"PeriodicalIF":0.0,"publicationDate":"2021-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39886556","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}