Frontiers in Molecular Biosciences最新文献

{"title":"Super-resolution microscopy to study membrane nanodomains and transport mechanisms in the plasma membrane","authors":"Yenisleidy de las Mercedes Zulueta Diaz, Eva C. Arnspang","doi":"10.3389/fmolb.2024.1455153","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1455153","url":null,"abstract":"Biological membranes are complex, heterogeneous, and dynamic systems that play roles in the compartmentalization and protection of cells from the environment. It is still a challenge to elucidate kinetics and real-time transport routes for molecules through biological membranes in live cells. Currently, by developing and employing super-resolution microscopy; increasing evidence indicates channels and transporter nano-organization and dynamics within membranes play an important role in these regulatory mechanisms. Here we review recent advances and discuss the major advantages and disadvantages of using super-resolution microscopy to investigate protein organization and transport within plasma membranes.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"31 1 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequencing technology in sarcopenia: current research progress and future trends","authors":"Yuxia Yang, Xiangji Meng, Xiaomei Dai, Jian Zhang, Jihang Dai, Jingcheng Wang, Wenyong Fei","doi":"10.3389/fmolb.2024.1309006","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1309006","url":null,"abstract":"BackgroundMuscle is an important tissue of the human body. Muscle atrophy is common in people of all ages, which will lead to human weakness and decline of motor function, which is one of the important causes of disability. The common methods of genomics research are transcriptome, proteomics and metabolomics, which are important means to explore the molecular pathology of diseases. In recent years, combinatorial research has been carried out on a large scale in the field of muscle atrophy. However, no author in this field has carried out bibliometrics and visual analysis.MethodsIn this study, articles related to the histological study of muscular dystrophy since 2000 were searched from the Web of Science core database (WoSCC). We will retrieve the results through CiteSpace, VosViewer and R for data statistics and visual analysis.ResultsIn this study, a total of 141 publications were collected, and the number of publications increased year by year. These 141 articles came from 1031 co-authors from 361 institutions in 31 countries and were published in 92 journals. A total of 6286 articles from 1383 journals were cited. Authors from American institutions have published the most articles and have been cited the most, and authors from other countries have also made considerable contributions.ConclusionThis is the first bibliometric and visual analysis of published research in the field of muscular dystrophy through systematic data retrieval and combined with a variety of bibliometric analysis tools. Through these data, we summarize the previous studies of scholars, and provide prospects for future research in the field.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"60 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α-Lipoic acid: a potential regulator of copper metabolism in Alzheimer’s disease","authors":"Sigrid Kirss, Anette Reinapu, Ekaterina Kabin, Julia Smirnova, Vello Tõugu, Peep Palumaa","doi":"10.3389/fmolb.2024.1451536","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1451536","url":null,"abstract":"Alzheimer’s disease (AD) is characterized by classic hallmarks such as amyloid plaques and neurofibrillary tangles, however, intensive research has broadened its scope to explore additional underlying mechanisms. Notably, disruptions in metal homeostasis, particularly involving copper, have gained significant attention. In AD pathology, an imbalance is evident: there is an excess of extracellular copper alongside a deficiency in intracellular copper in brain tissue. Our previous work demonstrated that α-lipoic acid (LA) can effectively shift copper from the extracellular space to the intracellular environment in a neuronal cell model. However, the precise mechanism of action and role of LA in copper metabolism remained elusive. In this study, we compared the cellular effects of LA with those of different synthetic copper-binding ligands: diethyldithiocarbamate (DETC), clioquinol (CQ), D-penicillamine (D-PA) and elesclomol (ES). Using differentiated SH-SY5Y cell culture as a neuronal model, we found that, unlike other synthetic compounds, natural ligand LA is not toxic in the presence of extracellular copper, even at high doses. LA gradually increased intracellular copper levels over 24 h. In contrast, DETC, CQ, and ES acted as fast copper ionophores, potentially explaining their higher toxicity compared to LA. D-PA did not facilitate copper uptake into cells. We demonstrated that a slow increase of LA inside the cells is enhanced in the presence of copper. Furthermore, the ability of LA to modulate the equilibrium of extra- and intracellular copper was evident when we added copper isotope <jats:sup>65</jats:sup>Cu. The ratio of copper isotopes changed rapidly, reflecting the impact of LA on the equilibrium of copper distribution without affecting the copper transport network. Our results provide compelling evidence that α-lipoic acid holds promise as a non-toxic agent capable of normalizing copper metabolism in Alzheimer’s disease.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"7 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular dynamics simulation of the brain-isolated single-domain antibody/nanobody from camels through in vivo phage display screening","authors":"Behnam Hasannejad-Asl, Hassan Hashemzadeh, Farkhondeh Pooresmaeil, Mehran Dabiri, Mohammad-Reza Pooresmaeil, Davoud Ahmadvand, Arshad Hosseini","doi":"10.3389/fmolb.2024.1414119","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1414119","url":null,"abstract":"IntroductionDuring the last decade, there has been a significant rise in the use of therapeutic antibodies or passive immunotherapy for treating various conditions like inflammation and cancer. However, these proteins face challenges reaching the brain and often require specialized delivery methods such as single-domain antibodies (sdAbs). Traditional antibodies struggle to efficiently cross the blood-brain barrier (BBB), hindering their effectiveness. Receptor-mediated transcytosis (RMT) offers a promising pathway for transporting large molecules essential for brain function and treatment across the BBB.MethodsSdAbs and peptide ligands with an affinity for RMT receptors are commonly employed to enhance the transport of biotherapeutics compounds across the BBB. This research used a sdAbs phage-displayed library from 13 <jats:italic>camelus dromedarius</jats:italic> samples to identify sdABs that specifically bind to and are internalized by human BBB endothelial cells (ECs) through <jats:italic>in vivo</jats:italic> panning.Results and discussionOne sdAb, defined as FB24, was isolated, sequenced, translated into an open reading frame (ORF), and subjected to three-dimensional (3D) modeling. Molecular docking and molecular dynamics simulations were carried out by the HADDOCK web server and GROMACS, respectively, to evaluate the interaction between FB24 and EC receptors <jats:italic>in silico</jats:italic>. The docking results revealed that FB24 exhibited binding activity against potential EC receptors with −1.7 to −2.7 ranged z score and maintained a stable structure. The docked complex of FB24-RAGE (receptor for advanced glycation end products, also known as advanced glycation end product receptor [AGER]) showed 18 hydrogen bonds and 213 non-bonded contacts. It was chosen for further analysis by molecular dynamics simulations by GROMACS. This complex showed a stable condition, and its root mean square deviation (RMSD) was 0.218 nm. The results suggest that FB24 could serve as a suitable carrier vector for transporting therapeutic and diagnostic agents across the BBB to the brain through a non-invasive route.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Death Receptor 5 (DR5) for imaging and treatment of primary bone and soft tissue tumors: an update of the literature","authors":"Zakareya Gamie, Anja Krippner-Heidenreich, Craig Gerrand, Kenneth Samora Rankin","doi":"10.3389/fmolb.2024.1384795","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1384795","url":null,"abstract":"BackgroundDeath Receptor 5 (DR5) is expressed on the surface of primary bone and soft tissue sarcoma cells, and its activation induces cell death primarily through apoptosis. The combination of DR5 agonists and commonly used chemotherapeutic agents, such as doxorubicin, can promote cell death. Currently, clinical trials are investigating the effectiveness of DR5 activation using new biological agents, such as bi-specific or tetravalent antibodies, in improving the survival of patients with relapsed or refractory cancers. Furthermore, investigations continue into the use of novel combination therapies to enhance DR5 response, for example, with inhibitor of apoptosis protein (IAP) antagonist agents [such as the second mitochondria-derived activator of caspase (SMAC) mimetics] and with immune checkpoint inhibitor anti-programmed death-ligand 1 (anti-PD-L1) or anti-programmed cell death-1 (anti-PD-1) antibodies. Other therapies include nanoparticle-mediated delivery of TRAIL plasmid DNA or TRAIL mRNA and stem cells as a vehicle for the targeted delivery of anti-cancer agents, such as TRAIL, to the tumor.Methodsscoping review of the literature from November 2017 to March 2024, utilizing PubMed and Google Scholar.ResultsNew agents under investigation include nanoTRAIL, anti-Kv10.1, multimeric IgM, and humanized tetravalent antibodies. Developments have been made to test novel agents, and imaging has been used to detect DR5 in preclinical models and patients. The models include 3D spheroids, genetically modified mouse models, a novel jaw osteosarcoma model, and patient-derived xenograft (PDX) animal models. There are currently two ongoing clinical trials focusing on the activation of DR5, namely, IGM-8444 and INBRX-109, which have progressed to phase 2. Further modifications of TRAIL delivery with fusion to single-chain variable fragments (scFv-TRAIL), directed against tumor-associated antigens (TAAs), and in the use of stem cells focus on targeted TRAIL delivery to cancer cells using bi-functional strategies.Conclusion<jats:italic>In vitro</jats:italic>, <jats:italic>in vivo</jats:italic>, and clinical trials, as well as advances in imaging and theranostics, indicate that targeting DR5 remains a valid strategy in the treatment of some relapsed and refractory cancers.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"10 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: New approaches toward understanding challenges in molecular virology: computational techniques and machine learning.","authors":"Srirupa Chakraborty,Kun Qu,Jayaraman Valadi","doi":"10.3389/fmolb.2024.1472796","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1472796","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"119 1","pages":"1472796"},"PeriodicalIF":5.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a nomogram for predicting advanced liver fibrosis in patients with chronic hepatitis B","authors":"Kexing Han, Jianfeng Wang, Xizhen Song, Luyang Kang, Junjie Lin, Qinggang Hu, Weijie Sun, Yufeng Gao","doi":"10.3389/fmolb.2024.1452841","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1452841","url":null,"abstract":"BackgroundThe progression of chronic hepatitis B (CHB) to liver fibrosis and even cirrhosis is often unknown to patients, but noninvasive markers capable of effectively identifying advanced liver fibrosis remains absent.ObjectiveBased on the results of liver biopsy, we aimed to construct a new nomogram to validate the stage of liver fibrosis in CHB patients by the basic information of CHB patients and routine laboratory tests.MethodsPatients with CHB diagnosed for the first time in the First Affiliated Hospital of Anhui Medical University from 2010 to 2018 were selected, and their basic information, laboratory tests and liver biopsy information were collected. Eventually, 974 patients were enrolled in the study, while all patients were randomized into a training cohort (n = 732) and an internal validation cohort (n = 242) according to a 3:1 ratio. In the training cohort, least absolute shrinkage and selection operator (Lasso) regression were used for predictor variable screening, and binary logistic regression analysis was used to build the diagnostic model, which was ultimately presented as a nomogram. The predictive accuracy of the nomograms was analyzed by running operating characteristic curve (ROC) to calculate area under curve (AUC), and the calibration was evaluated. Decision curve analysis (DCA) was used to determine patient benefit. In addition, we validated the built models with internal as well as external cohort (n = 771), respectively.ResultsUltimately, the training cohort, the internal validation cohort, and the external validation cohort contained sample sizes of 188, 53, and 149, respectively, for advanced liver fibrosis. Gender, albumin (Alb), globulin (Glb), platelets (PLT), alkaline phosphatase (AKP), glutamyl transpeptidase (GGT), and prothrombin time (PT) were screened as independent predictors. Compared with the aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and King’s score, the model in the training cohort (AUC = 0.834, 95% CI 0.800–0.868, <jats:italic>p</jats:italic> &amp;lt; 0.05) and internal validation cohort (AUC = 0.804, 95% CI 0.742–0.866, <jats:italic>p</jats:italic> &amp;lt; 0.05) showed the best discrimination and the best predictive performance. In addition, DCA showed that the clinical benefit of the nomogram was superior to the APRI, FIB-4 and King’s scores in all cohorts.ConclusionThis study constructed a validated nomogram model with predictors screened from clinical variables which could be easily used for the diagnosis of advanced liver fibrosis in CHB patients.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"102 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in understanding the molecular mechanisms of borderline ovarian tumors","authors":"Shiying Chen, Li Huang, Meili Liang, Yajing Xie, Zhimei Zhou, Yumin Ke, Zhuna Wu","doi":"10.3389/fmolb.2024.1429852","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1429852","url":null,"abstract":"Borderline ovarian tumors (BOTs), which are a special type of epithelial tumor of the ovary, lie between benign and malignant tumors and have low malignant potential. Due to the fact that the early symptoms of these tumors are relatively subtle, they are not easy to diagnose clinically. This study explores advancements in clinical detection methods and provides a comprehensive overview of molecules such as cell migration factors, cell transcription factors, cell damage repair factors, cell cycle regulators, and tumor suppressor genes that are related to the development of BOTs and their related mechanisms in recent years, thus aiming to provide more sensitive, specific, and efficient differential diagnosis and treatment plans for patients to improve their prognosis and survival outcomes.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"5 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome-based identification of key actin-binding proteins associated with high metastatic potential in breast cancer","authors":"Christian Müller, Leticia Oliveira-Ferrer, Volkmar Müller, Barbara Schmalfeldt, Sabine Windhorst","doi":"10.3389/fmolb.2024.1440276","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1440276","url":null,"abstract":"IntroductionActin-binding proteins (ABPs) are essential for the regulation of morphological plasticity required for tumor cells to metastasize. The aim of this study was to perform an unbiased bioinformatic approach to identify the key ABPs significantly associated with the metastatic potential of breast cancer cells.MethodsMicroarray data from 181 primary breast cancer samples from our hospital were used, and all genes belonging to the Gene Ontology term actin cytoskeleton organization were obtained from QuickGO. Association with metastasis-free survival probability was tested using Cox proportional hazards regression, and pairwise co-expression was tested by Pearson correlations. Differential expression between different subgroups was analyzed using Wilcoxon tests for dichotomous traits and Kruskal–Wallis tests for categorical traits. Validation was performed using four publicly available breast cancer datasets.Results<jats:italic>ARHGAP25</jats:italic> was significantly associated with a low metastatic potential, and <jats:italic>CFL1</jats:italic>, <jats:italic>TMSB15A</jats:italic>, and <jats:italic>ACTL8</jats:italic> were significantly associated with a high metastatic potential. A significantly higher expression of <jats:italic>CFL1</jats:italic>, <jats:italic>TMSB15A,</jats:italic> and <jats:italic>ACTL8</jats:italic> mRNA was found in the more aggressive Her2-positive and triple-negative subtypes as well as in ER-negative samples. Also, these genes were co-expressed in the same tumors. However, only mRNA levels of <jats:italic>CFL1</jats:italic> were increased in pN1 compared to pN0 patients. External validation revealed that <jats:italic>CFL1</jats:italic> and <jats:italic>TMSB15A</jats:italic> had significant associations with consistent hazard ratios in two breast cancer cohorts, and among these, <jats:italic>CFL1</jats:italic> exhibited the highest hazard ratios.Conclusion<jats:italic>CFL1</jats:italic> showed the strongest correlation with the metastatic potential of breast tumors. Thus, targeted inhibition of <jats:italic>CFL1</jats:italic> might be a promising approach to treat malignant breast cancer cells.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"3 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimetastatic and antitumor activities of oncolytic NDV AMHA1 in a 3D culture model of breast cancer","authors":"Ahmed Majeed Al-Shammari, Marwa Ibrahim Salman","doi":"10.3389/fmolb.2024.1331369","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1331369","url":null,"abstract":"IntroductionNewcastle disease virus (NDV) AMHA1 is capable of killing cancer cells by direct replication or induction of apoptosis alongside other pathways. In this study, we report the potent antimetastatic and anticancer activities of NDV AMHA1 in a 3D spheroid model of breast cancer metastasis.Methodswe used two breast cancer cell lines AMJ13 and MCF7 in our metastasis model system.ResultsFirst, we showed that NDV AMHA1 can infect and kill breast cancer cells in proliferating adherent cells and tumor spheroids using different virus doses and studying virus replication kinetics. We showed that NDV can infect and spread within the spheroids that represent metastasis before and after reattachment. Furthermore, we evaluated the ability of NDV to induce apoptosis in cancer spheroids and by virus tracking showed that NDV infection is essential for the elimination of these metastasis spheroids.DiscussionThe mechanism by which NDV induces cell killing in the metastasis model is the induction of caspase-3 and P21 and inhibition of Ki67 in cancer cells, but not in normal cells. In conclusion, these results indicate that NDV AMHA1 has the ability to kill breast cancer metastases in suspension or attached, and this is a novel finding of NDV AMHA1 being a possibly efficient therapy against human metastatic breast cancer.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"10 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220219","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}