Frontiers in bioscience (Landmark edition)最新文献

{"title":"Challenges in the Therapeutic Exploitation of Chemokine Receptor-Mediated Internalization of Nanocarriers.","authors":"Giuseppe Bardi","doi":"10.31083/j.fbl2910350","DOIUrl":"https://doi.org/10.31083/j.fbl2910350","url":null,"abstract":"<p><p>Chemokines are small proteins guiding cell migration with crucial role during immune responses. Their actions are mediated by 7-helix trans-membrane Gα protein-coupled receptors and ended by chemokine-receptor complex downregulation. Beyond its physiological role, ligand-induced receptor endocytosis can be exploited to vehiculate drugs and genetic materials within specific cells. Indeed, peptide-modified drugs and chemokine-decorated nanocarriers can target cell subpopulations significantly increasing cargo internalization. Carrier functionalization with small peptides or small-molecule-antagonists have been developed by different groups and proved their efficacy <i>in vivo</i>. One major limitation regards their restricted number of targeted receptors, although involved in diverse types of cancer and inflammatory diseases. Our group implemented nanoparticle decoration using whole chemokines, which in my opinion offer a versatile platform for precise drug delivery. The rationale relies on the broad and distinctive cellular expression of all chemokine receptors covering the different tissues, theoretically allowing chemokine-decorated particle delivery to any chosen cell subset. Although promising, our approach is still in its infancy and the experiments performed only <i>in vitro</i> so far. This manuscript briefly describes the established nanotechnologies for chemokine receptor-mediated delivery and, in greater details, our chemokine-decorated nanoparticles. Positive and negative aspects of the different approaches are also discussed, giving my opinion on why future nano-formulations could benefit from these chemo-attractant immune mediators.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"350"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549318","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":"Nanoengineered Platform-Based Microenvironment-Triggered Immunotherapy in Cancer Treatment.","authors":"Namdev Dhas, Ritu Kudarha, Sanjay Kulkarni, Soji Soman, Prerana D Navti, Jahnavi Kulkarni, Amrita Arup Roy, Viola Colaco, Ruchira Raychaudhuri, Ashutosh Gupta, Chandrakantsing Pardeshi, Dipak Bari, Ruchi Tiwari, Jayvadan Patel, Sudheer Moorkoth, Srinivas Mutalik","doi":"10.31083/j.fbl2910349","DOIUrl":"https://doi.org/10.31083/j.fbl2910349","url":null,"abstract":"<p><p>The immune system and cancer cells interact intricately during the growth of tumors, and the dynamic interplay between immune activation and suppression greatly influences the cancer outcome. Natural killer cells (NK), cytotoxic T lymphocytes (CTLs) and Dendritic cells (DC), employ diverse mechanisms, to combat cancer. However, the challenges posed by factors such as chronic inflammation and the immunosuppressive tumor microenvironment (TME) often hinder immune cells' ability to detect and eliminate tumors accurately. Immunotherapy offers a promising approach, reprogramming the immune system to target and eliminating cancer cells while minimizing side effects, enhancing immune memory, and lowering the risk of metastasis and relapse compared to traditional treatments like radiation and surgery. Nanotechnology presents a potential solution by enabling safer, more efficient drug delivery through nanoparticles. These nanoengineered drugs can be tailored for controlled activation and release. Improving TME characters holds potential for enhancing personalized immunotherapy and addressing T cell availability issues within tumor sites, particularly when combined with existing therapies. This review discusses TMEs and the strategies to overcome immunosuppression in TME, and various immune cell-based strategies to improve antitumor response. It also focuses on the strategies for constructing microenvironment responsive nanoplatforms based upon the factors present at higher levels in TME like acidic pH, hypoxia facilitated by poor oxygen supply, higher expression of certain enzymes, and other factors such light, ultrasound and magnetic field. Combination immune therapies combined with immunotherapy include photodynamic therapy, photothermal therapy, chemotherapy, gene therapy and radiotherapy, revealing a high level of anticancer activity in comparison to a single therapy, enhancing immunogenicity, promoting therapeutic efficacy, and lowering metastasis. In conclusion, cancer immunotherapy is a potential technique to combat cancer cells and boost the immune system, hindering their growth and recurrence. In order to prevent cancer, it helps the immune system target cancer cells selectively and strengthens its long-term memory. Clinical trials are extending the application of immunotherapy and identifying strategies to improve the immune system tumor-fighting capabilities. Immunotherapy has enormous promise and gives hope for more successful cancer treatment.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"349"},"PeriodicalIF":3.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549335","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":"Autophagy Alterations in White and Brown Adipose Tissues of Mice Exercised under Different Training Protocols.","authors":"Isaac Tamargo-Gómez, Manuel Fernández-Sanjurjo, Helena Codina-Martínez, Cristina Tomás-Zapico, Eduardo Iglesias-Gutiérrez, Benjamín Fernández-García, Álvaro F Fernández","doi":"10.31083/j.fbl2910348","DOIUrl":"https://doi.org/10.31083/j.fbl2910348","url":null,"abstract":"<p><strong>Background: </strong>Autophagy is a conserved catabolic process that promotes cellular homeostasis and health. Although exercise is a well-established inducer of this pathway, little is known about the effects of different types of training protocols on the autophagy levels of tissues that are tightly linked to age-related metabolic syndromes (like brown adipose tissue) but are not easily accessible in humans.</p><p><strong>Methods: </strong>Here, we take advantage of animal models to assess the effects of short- and long-term resistance and endurance training in both white and brown adipose tissue, reporting distinct alterations on autophagy proteins microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B, or LC3B) and sequestosome-1 (SQSTM1/p62). Additionally, we also analyzed the repercussions of these interventions in fat tissues of mice lacking autophagy-related protein 4 homolog B (ATG4B), further assessing the impact of exercise in these dynamic, regulatory organs when autophagy is limited.</p><p><strong>Results: </strong>In wild-type mice, both short-term endurance and resistance training protocols increased the levels of autophagy markers in white adipose tissue before this similarity diverges during long training, while autophagy regulation appears to be far more complex in brown adipose tissue. Meanwhile, in ATG4B-deficient mice, only resistance training could slightly increase the presence of lipidated LC3B, while p62 levels increased in white adipose tissue after short-term training but decreased in brown adipose tissue after long-term training.</p><p><strong>Conclusions: </strong>Altogether, our study suggests an intricated regulation of exercise-induced autophagy in adipose tissues that is dependent on the training protocol and the autophagy competence of the organism.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"348"},"PeriodicalIF":3.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549313","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":"Bioinformatics Identification and Validation of Angiogenesis-Related Genes in Myocardial Ischemic Reperfusion Injury.","authors":"Longfei Wu, Zhijiang Zhou, Yuheng Zeng, Shengli Yang, Qingying Zhang","doi":"10.31083/j.fbl2910347","DOIUrl":"https://doi.org/10.31083/j.fbl2910347","url":null,"abstract":"<p><strong>Background: </strong>Angiogenesis plays a critical protective role in myocardial ischemia-reperfusion injury (MIRI); however, therapeutic targeting of associated genes remains constrained. To bridge this gap, we conducted bioinformatics analysis to identify pivotal angiogenesis-related genes in MIRI, potentially applicable for preventive and therapeutic interventions.</p><p><strong>Methods: </strong>We collected two mouse heart I/R expression datasets (GSE61592 and GSE83472) from Gene Expression Omnibus, utilizing the Limma package to identify differentially expressed genes (DEGs). Angiogenesis-related genes (ARGs) were extracted from GeneCards, and their overlap with DEGs produced differentially expressed ARGs (ARDEGs). Further analyses included Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and disease ontology to explore biological functions. Weighted gene correlation network analysis (WGCNA) was used to investigate molecular modules linked to MIRI. Additionally, a protein-protein interaction (PPI) network was constructed to pinpoint hub genes relevant to MIRI. Receiver operating characteristic curves were used to assess the diagnostic efficacy of these hub genes for MIRI. An ischemia-reperfusion injury model was established using human cardiac microvascular endothelial cells (HCMECs), with the expression of hub genes validated within this experimental framework.</p><p><strong>Results: </strong>We identified 47 ARDEGs, 41 upregulated and 6 downregulated. PPI network analysis revealed suppressor of cytokine signaling 3 (<i>Socs3</i>), C-X-C motif chemokine ligand 1 (<i>Cxcl1</i>), interleukin 1 beta (<i>Il1b</i>), and matrix metallopeptidase 9 (<i>Mmp9</i>) as hub genes. Receiver operating characteristic (ROC) curve analysis demonstrated strong diagnostic potential for <i>Socs3</i>, <i>Cxcl1</i>, <i>Il1b</i>, and <i>Mmp9</i>. <i>In vitro</i> validation corroborated the mRNA and protein expression predictions.</p><p><strong>Conclusions: </strong>Our study highlights the pivotal role of <i>Socs3</i>, <i>Cxcl1</i>, <i>Il1b</i>, and <i>Mmp9</i> in MIRI development, their significance in immune cell infiltration, and their diagnostic accuracy. These findings offer valuable insights for MIRI diagnosis and treatment, presenting potential molecular targets for future research.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"347"},"PeriodicalIF":3.3,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549317","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":"Peripheral Biomarkers and Suicide: The Role of Neurotransmission, Neurotrophism, Neuroinflammation, and Neuroplasticity Dysregulation.","authors":"Donato Morena, Emanuela Turillazzi, Vittorio Fineschi","doi":"10.31083/j.fbl2910346","DOIUrl":"https://doi.org/10.31083/j.fbl2910346","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"346"},"PeriodicalIF":3.3,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549337","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":"Immune Thrombocytopenia: Immune Dysregulation and Genetic Perturbations Deciphering the Fate of Platelets.","authors":"Zahra Tariq, Muhammad Imran Qadeer, Khadija Zahid, Elena Vladimirovna Cherepkova, Sayakhat Taurbekovich Olzhayev","doi":"10.31083/j.fbl2910342","DOIUrl":"https://doi.org/10.31083/j.fbl2910342","url":null,"abstract":"<p><p>Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder. It involves impaired production and excessive destruction of platelets. It is a complex and heterogeneous disorder with unknown pathophysiology. Both genetic and immunologic perturbations have been implicated in the disease pathogenesis. Immune dysregulations involve both the humoral and cellular immunity. Attack of anti-platelet autoantibodies has been found to be the fundamental cause of platelet destruction. Other mechanisms including T cell mediated platelet destruction, complement activation, apoptosis, and desialylation have also been found in the development of ITP. Genetic testing has revealed various predispositions including single nucleotide polymorphisms (SNPs), copy number variations (CNVs), and epigenetic changes in the immunoregulatory genes of ITP subjects. Varying methylation patterns have also been found in the immune-related genes. This review summarizes the dysregulated immune cells, immunologic cascades, altered signaling pathways, genetic mutations and epigenetic changes in ITP pathogenesis. These alterations induce autoimmune responses against the platelets resulting in complex bleeding manifestations and onset of ITP.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"342"},"PeriodicalIF":3.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549332","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":"HOXD9 Enhances the Release of HMGB1 and Boosts Glycolysis in Glioblastoma under Hypoxic Conditions, Leading to Tumor Growth by Activating the Transcription of <i>PFKFB3</i>.","authors":"Guangzhi Xu, Jingchi Sun, Lizhou Wei, Xicai Yi, Fuxin Han, Weiping Liu","doi":"10.31083/j.fbl2910341","DOIUrl":"https://doi.org/10.31083/j.fbl2910341","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is an aggressive primary brain tumor. The <i>HOX</i> gene family has been implicated in the pathogenesis of different types of tumors. This research aimed to examine the impact of homeobox D9 (HOXD9) in GBM under hypoxic conditions, as well as to elucidate its underlying molecular mechanisms.</p><p><strong>Methods: </strong>The study assessed the differential expression of nine <i>HOXD</i> genes in GBM using the Mann-Whitney U test and identified genes with high correlation with the cancer genome atlas (TCGA)-GBM dataset using receiver operating characteristic (ROC) curves. Prognostic genes of GBM patients were identified through a combination of prognostic Kaplan-Meier (KM) curve and Cox analysis. <i>In vitro</i> experiments were conducted using U87-MG and U251-MG cells, and an animal GBM model was constructed. The study also measured the secretion level of high mobility group box 1 (HMGB1) using enzyme-linked immunosorbent assay (ELISA). Glucose uptake and lactate production levels in cells and tissues were analyzed using kits. The expressions of HOXD9 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) were detected by immunofluorescence, and chromatin immunoprecipitation (ChIP) validated their relationship.</p><p><strong>Results: </strong><i>HOXD9</i> was identified as the target gene, showing a significant correlation between HOXD9 expression and prognostic clinical outcomes. Overexpression of HMGB1 enhanced cell proliferation, migration, and the expression levels of HOXD9 and PFKFB3 and promoted HMGB1 secretion, glucose uptake, and lactate generation. HOXD9 bound to the <i>PFKFB3</i> promoter region in U87-MG and U251-MG cells. Furthermore, PFKFB3 overexpression partially counteracted the suppressive effects of HOXD9 silencing on tumor formation.</p><p><strong>Conclusion: </strong>HOXD9 promoted hypoxia-induced HMGB1 secretion and glycolysis in GBM through the transcriptional activation of <i>PFKFB3</i>, which in turn promoted tumorigenesis.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"341"},"PeriodicalIF":3.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549330","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":"Re-Assessing the Role of Platelet Activating Factor and Its Inflammatory Signaling and Inhibitors in Cancer and Anti-Cancer Strategies.","authors":"Alexandros Tsoupras, Theodora Adamantidi, Marios Argyrios Finos, Athanassios Philippopoulos, Paraskevi Detopoulou, Ifigeneia Tsopoki, Maria Kynatidou, Constantinos A Demopoulos","doi":"10.31083/j.fbl2910345","DOIUrl":"https://doi.org/10.31083/j.fbl2910345","url":null,"abstract":"<p><p>Since 2000s, we have outlined the multifaceted role of inflammation in several aspects of cancer, via specific inflammatory mediators, including the platelet activating factor (PAF) and PAF-receptor (PAFR) related signaling, which affect important inflammatory junctions and cellular interactions that are associated with tumor-related inflammatory manifestations. It is now well established that disease-related unresolved chronic inflammatory responses can promote carcinogenesis. At the same time, tumors themselves are able to promote their progression and metastasis, by triggering an inflammation-related vicious cycle, in which PAF and its signaling play crucial role(s), which usually conclude in tumor growth and angiogenesis. In parallel, new evidence suggests that PAF and its signaling also interact with several inflammation-related cancer treatments by inducing an antitumor immune response or, conversely, promoting tumor recurrence. Within this review article, the current knowledge and future perspectives of the implication of PAF and its signaling in all these important aspects of cancer are thoroughly re-assessed. The potential beneficial role of PAF-inhibitors and natural or synthetic modulators of PAF-metabolism against tumors, tumor progression and metastasis are evaluated. Emphasis is given to natural and synthetic molecules with dual anti-PAF and anti-cancer activities (Bio-DAPAC-tives), with proven evidence of their antitumor potency through clinical trials, as well as on metal-based anti-inflammatory mediators that constitute a new class of potent inhibitors. The way these compounds may promote anti-tumor effects and modulate the inflammatory cellular actions and immune responses is also discussed. Limitations and future perspectives on targeting of PAF, its metabolism and receptor, including PAF-related inflammatory signaling, as part(s) of anti-tumor strategies that involve inflammation and immune response(s) for an improved outcome, are also evaluated.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"345"},"PeriodicalIF":3.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549248","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":"Mechanistic Insights and Molecular Diagnostics of TMPRSS2-ERG: Overview of the Journey from Regulation of Signaling Landscape in Fusion Positive Prostate Cancer to Appraisal as a Diagnostic Marker.","authors":"Ammad Ahmad Farooqi, Assiya Turgambayeva, Aigul Almabayeva, Marina Zhanaliyeva, Lyazat Orakbay, Zhanara Shabanbayeva, Oryngul Narmanova, Marat Kelissovich Syzdykbayev","doi":"10.31083/j.fbl2910343","DOIUrl":"https://doi.org/10.31083/j.fbl2910343","url":null,"abstract":"<p><p>Chromosomal rearrangements and recurrent gene fusions were previously presumed to be the primary oncogenic mechanisms of hematological malignancies. However, the discovery of gene fusions in different cancers has opened new horizons to comprehensively investigate how cell type-specific fusion oncoproteins modulate signaling cascades. Prostate cancer (PCa) is a multifaceted and therapeutically challenging disease, and functional genomics have helped us develop a better understanding of the mechanisms underlying prostate carcinogenesis, castration-resistant PCa, and metastasis. Keeping in mind the fact that gene fusions have also been discovered in PCa, there has been rapid expansion in the field of molecular oncology and researchers are uncovering new facets regarding the mechanistic regulation of signaling pathways by fusion oncoproteins.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"343"},"PeriodicalIF":3.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549333","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":"Endocrine-Disrupting Chemicals: Do Polyphenols Advantage or Counteract Their Activity?","authors":"Monica Benvenuto, Chiara Focaccetti, Loredana Cifaldi, Roberto Bei","doi":"10.31083/j.fbl2910344","DOIUrl":"https://doi.org/10.31083/j.fbl2910344","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 10","pages":"344"},"PeriodicalIF":3.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549325","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}