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Evaluation of Peri-Implantitis through Fourier-Transform Infrared Spectroscopy on Saliva.
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-01-10 DOI: 10.1021/acs.jproteome.4c00707
Graziele Parize, Gabriele Nepomuceno, Jamil Shibli, Rafael Siroma, Matheus Willian Caetano, Yeon Jung Kim, Paulo Henrique Braz-Silva, Herculano Martinho, Debora Pallos
{"title":"Evaluation of Peri-Implantitis through Fourier-Transform Infrared Spectroscopy on Saliva.","authors":"Graziele Parize, Gabriele Nepomuceno, Jamil Shibli, Rafael Siroma, Matheus Willian Caetano, Yeon Jung Kim, Paulo Henrique Braz-Silva, Herculano Martinho, Debora Pallos","doi":"10.1021/acs.jproteome.4c00707","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00707","url":null,"abstract":"<p><strong>Background: </strong>Peri-implantitis is characterized as a pathological change in the tissues around dental implants. Fourier-transform infrared spectroscopy (FTIR) provides molecular information from optical phenomena observed by the vibration of molecules, which is used in biological studies to characterize changes and serves as a form of diagnosis.</p><p><strong>Aims: </strong>this case-control study evaluated the peri-implant disease by using FTIR spectroscopy with attenuated total reflectance in the fingerprint region.</p><p><strong>Methods: </strong>38 saliva samples were evaluated, 17 from the control group and 21 from the peri-implantitis group. Clinical data such as plaque index (PI), gingival index, probing depth (PS), and attachment level were assessed.</p><p><strong>Results: </strong>The results of clinical parameters showed a statistical difference between the two groups regarding an excess of the PI. In the FTIR-ATR analysis, the main components revealed vibrational modes of fatty acids, histidine, lipid esters, nucleic acids, and tryptophan, with the main molecules contributing to spectral discrimination. The five-component partial least-squares discriminant analysis classification model had an accuracy of 81%, showing differences between healthy and diseased implants.</p><p><strong>Conclusion: </strong>the FTIR spectroscopy provides important molecular characteristics of the samples and the results in association with clinical data show the effectiveness of using this tool for diagnosing the disease.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
mTOR Variants Activation Discovers PI3K-like Cryptic Pocket, Expanding Allosteric, Mutant-Selective Inhibitor Designs.
IF 5.6 2区 化学
Journal of Chemical Information and Modeling Pub Date : 2025-01-10 DOI: 10.1021/acs.jcim.4c02022
Yonglan Liu, Wengang Zhang, Hyunbum Jang, Ruth Nussinov
{"title":"mTOR Variants Activation Discovers PI3K-like Cryptic Pocket, Expanding Allosteric, Mutant-Selective Inhibitor Designs.","authors":"Yonglan Liu, Wengang Zhang, Hyunbum Jang, Ruth Nussinov","doi":"10.1021/acs.jcim.4c02022","DOIUrl":"https://doi.org/10.1021/acs.jcim.4c02022","url":null,"abstract":"<p><p>mTOR plays a crucial role in PI3K/AKT/mTOR signaling. We hypothesized that mTOR activation mechanisms driving oncogenesis can advise effective therapeutic designs. To test this, we combined cancer genomic analysis with extensive molecular dynamics simulations of mTOR oncogenic variants. We observed that conformational changes within mTOR kinase domain are associated with multiple mutational activation events. The mutations disturb the α-packing formed by the kαAL, kα3, kα9, kα9b, and kα10 helices in the kinase domain, creating cryptic pocket. Its opening correlates with opening of the catalytic cleft, including active site residues realignment, favoring catalysis. The cryptic pocket created by disrupted α-packing coincides with the allosteric pocket in PI3Kα can be harmoniously fitted by the PI3Kα allosteric inhibitor RLY-2608, suggesting that analogous drugs designed based on RLY-2608 can restore the packed α-structure, resulting in mTOR inactive conformation. Our results exemplify that knowledge of detailed kinase activation mechanisms can inform innovative allosteric inhibitor development.</p>","PeriodicalId":44,"journal":{"name":"Journal of Chemical Information and Modeling ","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the Potential of Nanocarriers for Cancer Immunotherapy: Insights into Mechanism, Nanocarriers, and Regulatory Perspectives.
IF 4.6
ACS Applied Bio Materials Pub Date : 2025-01-10 DOI: 10.1021/acsabm.4c01797
Tanmoy Kanp, Anish Dhuri, Bharath M, Khushi Rode, Mayur Aalhate, Priti Paul, Rahul Nair, Pankaj Kumar Singh
{"title":"Exploring the Potential of Nanocarriers for Cancer Immunotherapy: Insights into Mechanism, Nanocarriers, and Regulatory Perspectives.","authors":"Tanmoy Kanp, Anish Dhuri, Bharath M, Khushi Rode, Mayur Aalhate, Priti Paul, Rahul Nair, Pankaj Kumar Singh","doi":"10.1021/acsabm.4c01797","DOIUrl":"https://doi.org/10.1021/acsabm.4c01797","url":null,"abstract":"<p><p>Immunotherapy is a cutting-edge approach that leverages sophisticated technology to target tumor-specific antibodies and modulate the immune system to eradicate cancer and enhance patients' quality of life. Bioinformatics and genetic science advancements have made it possible to diagnose and treat cancer patients using immunotherapy technology. However, current immunotherapies against cancer have limited clinical benefits due to cancer-associated antigens, which often fail to interact with immune cells and exhibit insufficient therapeutic targeting with unintended side effects. To surmount this challenge, nanoparticle systems have emerged as a potential strategy for transporting immunotherapeutic agents to cancer cells and activating immune cells to combat tumors. Consequently, this process potentially generates an antigen-specific T cells response that effectively suppresses cancer growth. Furthermore, nanoplatforms have high specificity, efficacy, diagnostic potential, and imaging capabilities, making them promising tools for cancer treatment. However, this informative paper delves into the various available immunotherapies, including CAR T cells therapy and immune checkpoint blockade, cytokines, cancer vaccines, and monoclonal antibodies. Furthermore, the paper delves into the concept of theragnostic nanotechnology, which integrates therapy and diagnostics for a more personalized treatment approach for cancer therapy. Additionally, the paper covers the potential benefits of different nanocarrier systems, including marketed immunotherapy products, clinical trials, regulatory considerations, and future prospects for cancer immunotherapy.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941405","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
Candida glabrata: A Tale of Stealth and Endurance.
IF 4 2区 医学
ACS Infectious Diseases Pub Date : 2025-01-10 Epub Date: 2024-12-13 DOI: 10.1021/acsinfecdis.4c00477
Fizza Askari, Rupinder Kaur
{"title":"<i>Candida glabrata</i>: A Tale of Stealth and Endurance.","authors":"Fizza Askari, Rupinder Kaur","doi":"10.1021/acsinfecdis.4c00477","DOIUrl":"10.1021/acsinfecdis.4c00477","url":null,"abstract":"<p><p><i>Candida</i> (<i>Nakaseomyces</i>) <i>glabrata</i>, an opportunistic human fungal pathogen, causes mucosal and deep-seated infections in immunocompromised individuals. Recently designated as a high-priority fungal pathogen by the World Health Organization (WHO), <i>C. glabrata</i> exhibits low inherent susceptibility to azole antifungals. In addition, about 10% clinical isolates of <i>C. glabrata</i> display co-resistance to both azole and echinocandin drugs. Molecular mechanisms of antifungal resistance and virulence in <i>C. glabrata</i> are currently being delineated in-depth. This Review provides an overview of the epidemiology, biology, drug resistance, tools and host model systems for <i>C. glabrata</i>. Additionally, we discuss the immune evasion strategies that aid <i>C. glabrata</i> in establishing infections in the host. Overall, this Review aims to contribute to ongoing efforts to raise awareness of human pathogenic fungi, the growing threat of antifungal drug resistance and the unmet need for novel antifungal therapies, with an ultimate goal of improving clinical outcomes of affected individuals.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"4-20"},"PeriodicalIF":4.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prediction of Thermodynamic Properties of C60-Based Fullerenols Using Machine Learning.
IF 5.7 1区 化学
Journal of Chemical Theory and Computation Pub Date : 2025-01-10 DOI: 10.1021/acs.jctc.4c01438
Guiping Yang, Shu Zhang, Pei Zhao, Chuanhao Li, Lei Tang, Jun Jiang, Chong Zhao
{"title":"Prediction of Thermodynamic Properties of C<sub>60</sub>-Based Fullerenols Using Machine Learning.","authors":"Guiping Yang, Shu Zhang, Pei Zhao, Chuanhao Li, Lei Tang, Jun Jiang, Chong Zhao","doi":"10.1021/acs.jctc.4c01438","DOIUrl":"https://doi.org/10.1021/acs.jctc.4c01438","url":null,"abstract":"<p><p>Traditional machine learning methods face significant challenges in predicting the properties of highly symmetric molecules. In this study, we developed a machine learning model based on graph neural networks (GNNs) to accurately and swiftly predict the thermodynamic and photochemical properties of fullerenols, such as C<sub>60</sub>(OH)<i><sub>n</sub></i> (<i>n</i> = 1 to 30). First, we established a global method for generating fullerenol isomers through isomer fingerprinting, which can generate all possible isomers or produce diverse structural types on demand. Significantly, by incorporating interpretable descriptors such as atomic labels, bond lengths, and bond angles from highly symmetric isomers, our multilayer GNN model achieved over 90% accuracy in predicting the thermodynamic stability of fullerenols. The model also performed excellently in predicting electronic properties, including the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), and the energy gap. Overall, this work demonstrates a new strategy using interpretable descriptors for accurately predicting the properties of highly symmetric structures, offering theoretical chemists a valuable tool for studying these materials.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From Plant to Pathway: Molecular Mechanisms of Ruscogenin in Preventing Amyloid-Beta Aggregation through Computational and Experimental Approaches.
IF 4.1 3区 医学
ACS Chemical Neuroscience Pub Date : 2025-01-10 DOI: 10.1021/acschemneuro.4c00745
Aastha Tiwari, Ravinder Singh, Shubham Kumar, Aditya Sunkaria, Alok Jain
{"title":"From Plant to Pathway: Molecular Mechanisms of Ruscogenin in Preventing Amyloid-Beta Aggregation through Computational and Experimental Approaches.","authors":"Aastha Tiwari, Ravinder Singh, Shubham Kumar, Aditya Sunkaria, Alok Jain","doi":"10.1021/acschemneuro.4c00745","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00745","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, extracellular amyloid-β (Aβ) plaque accumulation, and intracellular neurofibrillary tangles. Recent efforts to find effective therapies have increased interest in natural compounds with multifaceted effects on AD pathology. This study explores natural compounds for their potential to mitigate AD pathology using molecular docking, ADME screening, and <i>in vitro</i> assays, with ruscogenin─a steroidal sapogenin from <i>Ruscus aculeatus─</i>emerging as a promising candidate. Ruscogenin, known for its antioxidant and anti-inflammatory properties, was investigated for its effects on Aβ aggregation, a critical process in AD progression. <i>In vitro</i> assays demonstrated that ruscogenin inhibits Aβ oligomerization at equimolar and higher molar ratios. Molecular dynamics (MD) simulations further revealed that ruscogenin targets aggregation-prone regions, reducing noncovalent interactions and the solvent-accessible surface area of Aβ aggregates. These effects were concentration-dependent, with higher concentrations yielding optimal inhibition, pointing to a multiphasic behavior in ruscogenin's modulation of Aβ aggregation. This study highlights ruscogenin's potential as a natural therapeutic agent for AD, capable of addressing both oxidative stress and inflammation. The findings lay the groundwork for further exploration of ruscogenin-based interventions and underscore the broader potential of natural compounds in AD treatment strategies.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
99mTc-DTPA-Collagen Radiotracer for the Noninvasive Detection of Infective Endocarditis.
IF 4 2区 医学
ACS Infectious Diseases Pub Date : 2025-01-10 Epub Date: 2024-12-08 DOI: 10.1021/acsinfecdis.4c00460
Mario González-Arjona, Gorka Sobrino, Lorena Cussó, María Guembe, Daniel Calle, Francisco Díaz Crespo, Emilio Bouza, Patricia Muñoz, Manuel Desco, Beatriz Salinas
{"title":"<sup>99m</sup>Tc-DTPA-Collagen Radiotracer for the Noninvasive Detection of Infective Endocarditis.","authors":"Mario González-Arjona, Gorka Sobrino, Lorena Cussó, María Guembe, Daniel Calle, Francisco Díaz Crespo, Emilio Bouza, Patricia Muñoz, Manuel Desco, Beatriz Salinas","doi":"10.1021/acsinfecdis.4c00460","DOIUrl":"10.1021/acsinfecdis.4c00460","url":null,"abstract":"<p><p>Infective endocarditis (IE) represents a significant concern among hospital-acquired infections, frequently caused by the Gram-positive bacterium <i>Staphylococcus aureus</i>. Nuclear imaging is emerging as a noninvasive and precise diagnostic tool. However, the gold standard radiotracer [<sup>18</sup>F]-FDG cannot distinguish between infection and inflammation, resulting in false positives. Based on the presence of collagen-binding proteins in the cell wall of <i>S. aureus</i>, we propose the radiolabeling of collagen for its evaluation in IE animal models by single-photon emission computed tomography (SPECT) imaging. We radiolabeled rat tail collagen I using DTPA chelator and [<sup>99m</sup>Tc]NaTcO<sub>4</sub>. Selectivity was evaluated in vitro using 3 Gram-positive bacteria, 1 Gram-negative bacteria and 1 yeast. In vivo SPECT/computed tomography (CT) imaging was conducted on 8 SD rat models of IE and 8 sterile sham model as controls. Ex vivo biodistribution and autoradiography were performed following imaging. Diagnosis of IE was confirmed through microbiological studies and H&E histopathology. [<sup>99m</sup>Tc]-DTPA-Collagen was synthesized successfully with a yield of 42.86 ± 6.35%, a purity of 95.84 ± 1.85% and a stability higher than 90% after 50 h postincubation. In vitro uptake demonstrated the selectivity for Gram-positive bacteria (63.85 ± 15.15%). Ex vivo analysis confirmed hepato-splenic excretion. In vivo SPECT/CT imaging revealed highly localized uptake within the aortic valve with a sensitivity of 62.5% and specificity of 87.5%. We successfully synthesized and characterized a new SPECT radiotracer based on [<sup>99m</sup>Tc]Tc-radiolabeled collagen. In vitro studies demonstrated the selectivity of the radiotracer for Gram-positive bacteria. In vivo SPECT/CT-based assessment in an IE model confirmed the potential of this approach to detect active IE.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"121-130"},"PeriodicalIF":4.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Designing Highly Potent Side-Chain Lactam-Bridged Cyclic Competence-Stimulating Peptide-Based Quorum-Sensing Modulators in Streptococcus oligofermentans.
IF 4 2区 医学
ACS Infectious Diseases Pub Date : 2025-01-10 Epub Date: 2024-12-17 DOI: 10.1021/acsinfecdis.4c00773
Uttam Ghosh, Yftah Tal-Gan
{"title":"Designing Highly Potent Side-Chain Lactam-Bridged Cyclic Competence-Stimulating Peptide-Based Quorum-Sensing Modulators in <i>Streptococcus oligofermentans</i>.","authors":"Uttam Ghosh, Yftah Tal-Gan","doi":"10.1021/acsinfecdis.4c00773","DOIUrl":"10.1021/acsinfecdis.4c00773","url":null,"abstract":"<p><p><i>Streptococcus oligofermentans</i>, a Gram-positive bacterium found in the oral microbiome, shows promise as an oral probiotic for preventing dental caries. It exhibits a reverse correlation with <i>Streptococcus mutans</i>, a key caries-causing pathogen, likely due to its production of hydrogen peroxide, a process mediated by quorum sensing (QS). In this work, we set out to develop novel lactam-based cyclic analogues of the competence stimulating peptide (CSP) signal utilized by <i>S. oligofermentans</i> for QS activation. To this end, we first conducted a ring position scan, where we determined the best positions within the CSP sequence to use for macrolactamization. We then conducted systematic ring size and bridge position scans to fine-tune the cyclic peptide conformation and identified a cyclic analogue, CSP-cyc(K2E2), with enhanced biological activity, 7-fold more active than the native CSP signal. This analogue also exhibited improved stability toward enzymatic degradation, demonstrating this analogue's potential utility as a chemical probe to study interspecies interactions between oral microbes and as a potential therapeutic agent. Overall, our lead cyclic analogue could be applied to augment the biotherapeutic potential of <i>S. oligofermentans</i> against <i>S. mutans</i> infections.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"197-203"},"PeriodicalIF":4.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Edaravone Improves Motor Dysfunction Following Brachial Plexus Avulsion Injury in Rats.
IF 4.1 3区 医学
ACS Chemical Neuroscience Pub Date : 2025-01-10 DOI: 10.1021/acschemneuro.4c00717
Sijing Li, Lin Wu, Juan Xie, Guijuan Zhou, Xuanwei Wen, Limin Deng, Shudong Lin, Guozhi Liu, Shuangxi Chen, Zijian Xiao
{"title":"Edaravone Improves Motor Dysfunction Following Brachial Plexus Avulsion Injury in Rats.","authors":"Sijing Li, Lin Wu, Juan Xie, Guijuan Zhou, Xuanwei Wen, Limin Deng, Shudong Lin, Guozhi Liu, Shuangxi Chen, Zijian Xiao","doi":"10.1021/acschemneuro.4c00717","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00717","url":null,"abstract":"<p><p>Brachial plexus root avulsion (BPRA) is often caused by road collisions, leading to total loss of motor function in the upper limb. At present, effective treatment options remain limited. Edaravone (EDA), a substance that eliminates free radicals, exhibits numerous biological properties, including neuroprotective, antioxidant and anti-inflammatory effects. However, the specific role and molecular mechanisms of EDA in the treatment of BPRA remain to be fully elucidated. The present study used a rat model of BPRA, following avulsion of the fifth, sixth and seventh cervical (C5, C6 and C7) anterior roots. Notably, C6 was replanted following a subcutaneous injection of either saline or 30 mg/kg/day EDA for seven continuous days. Subsequently, behavioral, histochemical, Western blot and reverse transcription-quantitative PCR (RT-PCR) analyses were conducted. Results of the present study revealed that treatment with EDA improves motor dysfunction, indicated by the increased Grooming test score, usage of the affected limb, and Irvine, Beatties and Bresnahan (IBB) score, following BPRA. In addition, EDA reduced the death of motoneurons (MNs), indicated by the increased number of Nissl-positive neuron, at the site of the affected limb, inhibited neuroinflammation and cellular pyroptosis, indicated by the decreased expression levels of IL-1β, IL-6, TNF-α, IL-18, p-p65, NLRP3, GSDMD and Caspase-1, improved the morphology of the abnormal myocutaneous nerve fibers, promoted axon remyelination, indicated by increased mRNA expression levels of remyelination-associated genes, including egr2, GAP-43, hmgcr, L1CAM, mpz, pmp22 and prx and demyelination-associated genes, including ngfr, notch1, pou3f1 and sox2, and alleviated muscle atrophy, indicated by the increased weight and volume of biceps brachii muscle, and the decreased number of fibroblasts and increased diameters in the fibers. Collectively, results of the present study suggested that EDA may support axonal remyelination and inhibit pyroptosis-associated neuroinflammation, enhancing MN survival and facilitating functional motor recovery. Thus, the present study may provide a novel theoretical basis for the use of EDA in the treatment of BPRA.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeted NIR Fluorescent Mechanically Interlocked Molecules-Peptide Bioconjugate for Live Cancer Cells Submitochondrial Stimulated Emission Depletion Super-Resolution Microscopy.
IF 4 2区 化学
Bioconjugate Chemistry Pub Date : 2025-01-10 DOI: 10.1021/acs.bioconjchem.4c00476
Samiran Kar, Rabi Sankar Das, Tapas Bera, Shreya Das, Ayan Mukherjee, Aniruddha Mondal, Arunima Sengupta, Samit Guha
{"title":"Targeted NIR Fluorescent Mechanically Interlocked Molecules-Peptide Bioconjugate for Live Cancer Cells Submitochondrial Stimulated Emission Depletion Super-Resolution Microscopy.","authors":"Samiran Kar, Rabi Sankar Das, Tapas Bera, Shreya Das, Ayan Mukherjee, Aniruddha Mondal, Arunima Sengupta, Samit Guha","doi":"10.1021/acs.bioconjchem.4c00476","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00476","url":null,"abstract":"<p><p>Herein, a water-soluble, ultrabright, near-infrared (NIR) fluorescent, mechanically interlocked molecules (MIMs)-peptide bioconjugate is designed with dual targeting capabilities. Cancer cell surface overexpressed α<sub>V</sub>β<sub>3</sub> integrin targeting two RGDS tetrapeptide residues is tethered at the macrocycle of MIMs-peptide bioconjugate via Cu(I)-catalyzed click chemistry on the Wang resin, and mitochondria targeting lipophilic cationic TPP<sup>+</sup> functionality is conjugated at the axle dye. Living carcinoma cell selective active targeting, subsequently cell penetration, mitochondrial imaging, including the ultrastructure of cristae, and real-time tracking of malignant mitochondria by MIMs-peptide bioconjugate (RGDS)<sub>2</sub>-Mito-MIMs-TPP<sup>+</sup> are established by stimulated emission depletion (STED) super-resolved fluorescence microscopy. Water-soluble NIR (RGDS)<sub>2</sub>-Mito-MIMs-TPP<sup>+</sup> is an effective class of MIMs-peptide bioconjugate with promising photophysics; for instance, remarkable photostability and thermal stability, strong and narrow NIR abs/em bands with high quantum yield, ultrabrightness, decent fluorescence lifetime, reasonable stability against cellular nucleophiles, biocompatibility, noncytotoxicity, and dual-targeted living cancer cell submitochondrial imaging ability are all indispensable criteria for targeted super-resolved STED microscopy.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","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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