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Extracellular vesicle therapy in neurological disorders. 神经系统疾病的细胞外囊泡疗法。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2024-08-25 DOI: 10.1186/s12929-024-01075-w
Napasiri Putthanbut, Jea Young Lee, Cesario V Borlongan
{"title":"Extracellular vesicle therapy in neurological disorders.","authors":"Napasiri Putthanbut, Jea Young Lee, Cesario V Borlongan","doi":"10.1186/s12929-024-01075-w","DOIUrl":"10.1186/s12929-024-01075-w","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are vital for cell-to-cell communication, transferring proteins, lipids, and nucleic acids in various physiological and pathological processes. They play crucial roles in immune modulation and tissue regeneration but are also involved in pathogenic conditions like inflammation and degenerative disorders. EVs have heterogeneous populations and cargo, with numerous subpopulations currently under investigations. EV therapy shows promise in stimulating tissue repair and serving as a drug delivery vehicle, offering advantages over cell therapy, such as ease of engineering and minimal risk of tumorigenesis. However, challenges remain, including inconsistent nomenclature, complex characterization, and underdeveloped large-scale production protocols. This review highlights the recent advances and significance of EVs heterogeneity, emphasizing the need for a better understanding of their roles in disease pathologies to develop tailored EV therapies for clinical applications in neurological disorders.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"85"},"PeriodicalIF":9.0,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Machine learning enabled classification of lung cancer cell lines co-cultured with fibroblasts with lightweight convolutional neural network for initial diagnosis. 利用轻量级卷积神经网络对与成纤维细胞共培养的肺癌细胞系进行机器学习分类,以进行初步诊断。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2024-08-23 DOI: 10.1186/s12929-024-01071-0
Adam Germain, Alex Sabol, Anjani Chavali, Giles Fitzwilliams, Alexa Cooper, Sandra Khuon, Bailey Green, Calvin Kong, John Minna, Young-Tae Kim
{"title":"Machine learning enabled classification of lung cancer cell lines co-cultured with fibroblasts with lightweight convolutional neural network for initial diagnosis.","authors":"Adam Germain, Alex Sabol, Anjani Chavali, Giles Fitzwilliams, Alexa Cooper, Sandra Khuon, Bailey Green, Calvin Kong, John Minna, Young-Tae Kim","doi":"10.1186/s12929-024-01071-0","DOIUrl":"10.1186/s12929-024-01071-0","url":null,"abstract":"<p><strong>Background: </strong>Identification of lung cancer subtypes is critical for successful treatment in patients, especially those in advanced stages. Many advanced and personal treatments require knowledge of specific mutations, as well as up- and down-regulations of genes, for effective targeting of the cancer cells. While many studies focus on individual cell structures and delve deeper into gene sequencing, the present study proposes a machine learning method for lung cancer classification based on low-magnification cancer outgrowth patterns in a 2D co-culture environment.</p><p><strong>Methods: </strong>Using a magnetic well plate holder, circular pattern lung cancer cell clusters were generated among fibroblasts, and daily images were captured to monitor cancer outgrowth over a 9-day period. These outgrowth images were then augmented and used to train a convolutional neural network (CNN) model based on the lightweight TinyVGG architecture. The model was trained with pairs of classes representing three subtypes of NSCLC: A549 (adenocarcinoma), H520 (squamous cell carcinoma), and H460 (large cell carcinoma). The objective was to assess whether this lightweight machine learning model could accurately classify the three lung cancer cell lines at different stages of cancer outgrowth. Additionally, cancer outgrowth images of two patient-derived lung cancer cells, one with the KRAS oncogene and the other with the EGFR oncogene, were captured and classified using the CNN model. This demonstration aimed to investigate the translational potential of machine learning-enabled lung cancer classification.</p><p><strong>Results: </strong>The lightweight CNN model achieved over 93% classification accuracy at 1 day of outgrowth among A549, H460, and H520, and reached 100% classification accuracy at 7 days of outgrowth. Additionally, the model achieved 100% classification accuracy at 4 days for patient-derived lung cancer cells. Although these cells are classified as Adenocarcinoma, their outgrowth patterns vary depending on their oncogene expressions (KRAS or EGFR).</p><p><strong>Conclusions: </strong>These results demonstrate that the lightweight CNN architecture, operating locally on a laptop without network or cloud connectivity, can effectively create a machine learning-enabled model capable of accurately classifying lung cancer cell subtypes, including those derived from patients, based upon their outgrowth patterns in the presence of surrounding fibroblasts. This advancement underscores the potential of machine learning to enhance early lung cancer subtyping, offering promising avenues for improving treatment outcomes in advanced stage-patients.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"84"},"PeriodicalIF":9.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Beyond glycan barriers: non-cognate ligands and protein mimicry approaches to elicit broadly neutralizing antibodies for HIV-1. 超越糖屏障:非识别配体和蛋白质模拟方法诱导 HIV-1 广泛中和抗体。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2024-08-21 DOI: 10.1186/s12929-024-01073-y
Stephen Ian Walimbwa, Petr Maly, Leona Raskova Kafkova, Milan Raska
{"title":"Beyond glycan barriers: non-cognate ligands and protein mimicry approaches to elicit broadly neutralizing antibodies for HIV-1.","authors":"Stephen Ian Walimbwa, Petr Maly, Leona Raskova Kafkova, Milan Raska","doi":"10.1186/s12929-024-01073-y","DOIUrl":"10.1186/s12929-024-01073-y","url":null,"abstract":"<p><p>Human immunodeficiency virus type 1 (HIV-1) vaccine immunogens capable of inducing broadly neutralizing antibodies (bNAbs) remain obscure. HIV-1 evades immune responses through enormous diversity and hides its conserved vulnerable epitopes on the envelope glycoprotein (Env) by displaying an extensive immunodominant glycan shield. In elite HIV-1 viremic controllers, glycan-dependent bNAbs targeting conserved Env epitopes have been isolated and are utilized as vaccine design templates. However, immunological tolerance mechanisms limit the development of these antibodies in the general population. The well characterized bNAbs monoclonal variants frequently exhibit extensive levels of somatic hypermutation, a long third heavy chain complementary determining region, or a short third light chain complementarity determining region, and some exhibit poly-reactivity to autoantigens. This review elaborates on the obstacles to engaging and manipulating the Env glycoprotein as an effective immunogen and describes an alternative reverse vaccinology approach to develop a novel category of bNAb-epitope-derived non-cognate immunogens for HIV-1 vaccine design.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"83"},"PeriodicalIF":9.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Plexin C1 influences immune response to intracellular LPS and survival in murine sepsis. Plexin C1 影响对细胞内 LPS 的免疫反应和小鼠败血症的存活率。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2024-08-21 DOI: 10.1186/s12929-024-01074-x
Alice Bernard, Claudia Eggstein, Linyan Tang, Marius Keller, Andreas Körner, Valbona Mirakaj, Peter Rosenberger
{"title":"Plexin C1 influences immune response to intracellular LPS and survival in murine sepsis.","authors":"Alice Bernard, Claudia Eggstein, Linyan Tang, Marius Keller, Andreas Körner, Valbona Mirakaj, Peter Rosenberger","doi":"10.1186/s12929-024-01074-x","DOIUrl":"10.1186/s12929-024-01074-x","url":null,"abstract":"<p><strong>Background: </strong>Intracellular sensing of lipopolysaccharide (LPS) is essential for the immune response against gram-negative bacteria and results in activation of caspase-11 and pyroptotic cell death with fatal consequences in sepsis. We found the neuronal guidance receptor plexin C1 (PLXNC1) influences the intracellular response to LPS.</p><p><strong>Methods: </strong>We employed a murine model of sepsis via cecal ligation and binding (CLP), using PLXNC1-/- mice and littermate controls, and additionally transfected murine bone-marrow-derived macrophages (BMDMs) from both genotypes with LPS to achieve activation of the noncanonical inflammasome ex vivo. Additionally, we transfected the PLXNC1 ligand SL4c-d in vivo and ex vivo to examine its effect on intracellular LPS response.</p><p><strong>Results: </strong>We found the neuronal guidance receptor PLXNC1 dampens the intracellular response to LPS by interacting with adenylate cyclase 4 (ADCY4) and protein kinase A activity, which in turn diminishes caspase-11 expression. The absence of PLXNC1 results in excessive inflammation marked by increased cytokine release, increased secondary organ injury and reduced sepsis survival in a murine sepsis model induced by CLP. Notably, administration of SL4c-d-peptide ligand of PLXNC1-reduces the inflammatory response during CLP-induced sepsis and improves survival.</p><p><strong>Conclusions: </strong>These results elucidate a previously unknown mechanism for PLXNC1 suppressing excessive noncanonical inflammasome activity and offer a new potential target for treatment of sepsis with its detrimental effects.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"82"},"PeriodicalIF":9.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
EpCAM-targeted betulinic acid analogue nanotherapy improves therapeutic efficacy and induces anti-tumorigenic immune response in colorectal cancer tumor microenvironment. EpCAM靶向白桦脂酸类似物纳米疗法可提高疗效并诱导结直肠癌肿瘤微环境中的抗肿瘤免疫反应。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2024-08-20 DOI: 10.1186/s12929-024-01069-8
Debasmita Dutta, Ashique Al Hoque, Brahamacharry Paul, Jun Hyoung Park, Chinmay Chowdhury, Mohiuddin Quadir, Soumyabrata Banerjee, Arghadip Choudhury, Soumik Laha, Nayim Sepay, Priyanka Boro, Benny Abraham Kaipparettu, Biswajit Mukherjee
{"title":"EpCAM-targeted betulinic acid analogue nanotherapy improves therapeutic efficacy and induces anti-tumorigenic immune response in colorectal cancer tumor microenvironment.","authors":"Debasmita Dutta, Ashique Al Hoque, Brahamacharry Paul, Jun Hyoung Park, Chinmay Chowdhury, Mohiuddin Quadir, Soumyabrata Banerjee, Arghadip Choudhury, Soumik Laha, Nayim Sepay, Priyanka Boro, Benny Abraham Kaipparettu, Biswajit Mukherjee","doi":"10.1186/s12929-024-01069-8","DOIUrl":"10.1186/s12929-024-01069-8","url":null,"abstract":"<p><strong>Background: </strong>Betulinic acid (BA) has been well investigated for its antiproliferative and mitochondrial pathway-mediated apoptosis-inducing effects on various cancers. However, its poor solubility and off-target activity have limited its utility in clinical trials. Additionally, the immune modulatory role of betulinic acid analogue in the tumor microenvironment (TME) is largely unknown. Here, we designed a potential nanotherapy for colorectal cancer (CRC) with a lead betulinic acid analogue, named as 2c, carrying a 1,2,3-triazole-moiety attached to BA through a linker, found more effective than BA for inhibiting CRC cell lines, and was chosen here for this investigation. Epithelial cell adhesion molecule (EpCAM) is highly overexpressed on the CRC cell membrane. A single-stranded short oligonucleotide sequence, aptamer (Apt), that folds into a 3D-defined architecture can be used as a targeting ligand for its specific binding to a target protein. EpCAM targeting aptamer was designed for site-specific homing of aptamer-conjugated-2c-loaded nanoparticles (Apt-2cNP) at the CRC tumor site to enhance therapeutic potential and reduce off-target toxicity in normal cells. We investigated the in vitro and in vivo therapeutic efficacy and anti-tumorigenic immune response of aptamer conjugated nanotherapy in CRC-TME.</p><p><strong>Methods: </strong>After the characterization of nanoengineered aptamer conjugated betulinic acid nanotherapy, we evaluated therapeutic efficacy, tumor targeting efficiency, and anti-tumorigenic immune response using cell-based assays and mouse and rat models.</p><p><strong>Results: </strong>We found that Apt-2cNP improved drug bioavailability, enhanced its biological half-life, improved antiproliferative activity, and minimized off-target cytotoxicity. Importantly, in an in vivo TME, Apt-2cNP showed promising signs of anti-tumorigenic immune response (increased mDC/pDC ratio, enhanced M1 macrophage population, and CD8 T-cells). Furthermore, in vivo upregulation of pro-apoptotic while downregulation of anti-apoptotic genes and significant healing efficacy on cancer tissue histopathology suggest that Apt-2cNP had predominantly greater therapeutic potential than the non-aptamer-conjugated nanoparticles and free drug. Moreover, we observed greater tumor accumulation of the radiolabeled Apt-2cNP by live imaging in the CRC rat model.</p><p><strong>Conclusions: </strong>Enhanced therapeutic efficacy and robust anti-tumorigenic immune response of Apt-2cNP in the CRC-TME are promising indicators of its potential as a prospective therapeutic agent for managing CRC. However, further studies are warranted.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"81"},"PeriodicalIF":9.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era. 低水平的 HIV-1 病毒血症会影响 INSTI 时代长期接受治疗的成年人的 T 细胞活化和衰老。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2024-08-19 DOI: 10.1186/s12929-024-01064-z
Violeta Lara-Aguilar, Manuel Llamas-Adán, Óscar Brochado-Kith, Celia Crespo-Bermejo, Sergio Grande-García, Sonia Arca-Lafuente, Ignacio de Los Santos, Carmen Prado, Mario Alía, Coral Sainz-Pinós, Amanda Fernández-Rodríguez, Luz Martín-Carbonero, Ricardo Madrid, Verónica Briz
{"title":"Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era.","authors":"Violeta Lara-Aguilar, Manuel Llamas-Adán, Óscar Brochado-Kith, Celia Crespo-Bermejo, Sergio Grande-García, Sonia Arca-Lafuente, Ignacio de Los Santos, Carmen Prado, Mario Alía, Coral Sainz-Pinós, Amanda Fernández-Rodríguez, Luz Martín-Carbonero, Ricardo Madrid, Verónica Briz","doi":"10.1186/s12929-024-01064-z","DOIUrl":"10.1186/s12929-024-01064-z","url":null,"abstract":"<p><strong>Background: </strong>Around 10% of people with HIV (PWH) exhibit a low-level viremia (LLV) under antiretroviral therapy (ART). However, its origin and clinical significance are largely unknown, particularly at viremias between 50 and 200 copies/mL and under modern ART based on integrase strand transfer inhibitors (INSTIs). Our aim was to characterize their poor immune response against HIV in comparison to individuals with suppressed viremia (SV) and non-HIV controls (NHC).</p><p><strong>Methods: </strong>Transversal observational study in 81 matched participants: 27 PWH with LLV, 27 PWH with SV, and 27 NHC. Activation (CD25, HLA-DR, and CD38) and senescence [CD57, PD1, and HAVCR2 (TIM3)] were characterized in peripheral T-cell subsets by spectral flow cytometry. 45 soluble biomarkers of systemic inflammation were evaluated by immunoassays. Differences in cell frequencies and plasma biomarkers among groups were evaluated by a generalized additive model for location, scale, and shape (GAMLSS) and generalized linear model (GLM) respectively, adjusted by age, sex at birth, and ART regimen.</p><p><strong>Results: </strong>The median age was 53 years and 77.8% were male. Compared to NHC, PWH showed a lower CD4+/CD8+ ratio and increased activation, senescence, and inflammation, highlighting IL-13 in LLV. In addition, LLV showed a downtrend in the frequency of CD8+ naive and effector memory (EM) type 1 compared to SV, along with higher activation and senescence in CD4+ and CD8+ EM and terminally differentiated effector memory RA+ (TEMRA) subpopulations. No significant differences in systemic inflammation were observed between PWH groups.</p><p><strong>Conclusion: </strong>LLV between 50 and 200 copies/mL leads to reduced cytotoxic activity and T-cell dysfunction that could affect cytokine production, being unable to control and eliminate infected cells. The increase in senescence markers suggests a progressive loss of immunological memory and a reduction in the proliferative capacity of immune cells. This accelerated immune aging could lead to an increased risk of developing future comorbidities. These findings strongly advocate for heightened surveillance of these PWH to promptly identify potential future complications.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"80"},"PeriodicalIF":9.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gene therapy for ultrarare diseases: a geneticist's perspective. 超级罕见病的基因治疗:遗传学家的视角。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2024-08-13 DOI: 10.1186/s12929-024-01070-1
Wuh-Liang Hwu
{"title":"Gene therapy for ultrarare diseases: a geneticist's perspective.","authors":"Wuh-Liang Hwu","doi":"10.1186/s12929-024-01070-1","DOIUrl":"10.1186/s12929-024-01070-1","url":null,"abstract":"<p><p>Gene therapy has made considerable strides in recent years. More than 4000 protein-coding genes have been implicated in more than 6000 genetic diseases; next-generation sequencing has dramatically revolutionized the diagnosis of genetic diseases. Most genetic diseases are considered very rare or ultrarare, defined here as having fewer than 1:100,000 cases, but only one of the 12 approved gene therapies (excluding RNA therapies) targets an ultrarare disease. This article explores three gene supplementation therapy approaches suitable for various rare genetic diseases: lentiviral vector-modified autologous CD34<sup>+</sup> hematopoietic stem cell transplantation, systemic delivery of adeno-associated virus (AAV) vectors to the liver, and local AAV delivery to the cerebrospinal fluid and brain. Together with RNA therapies, we propose a potential business model for these gene therapies.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"79"},"PeriodicalIF":9.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeted nanotherapeutics for the treatment of Helicobacter pylori infection. 治疗幽门螺旋杆菌感染的靶向纳米疗法。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2024-08-11 DOI: 10.1186/s12929-024-01068-9
Rute Chitas, Diana R Fonseca, Paula Parreira, M Cristina L Martins
{"title":"Targeted nanotherapeutics for the treatment of Helicobacter pylori infection.","authors":"Rute Chitas, Diana R Fonseca, Paula Parreira, M Cristina L Martins","doi":"10.1186/s12929-024-01068-9","DOIUrl":"10.1186/s12929-024-01068-9","url":null,"abstract":"<p><p>Helicobacter pylori infection is involved in gastric diseases such as peptic ulcer and adenocarcinoma. Approved antibiotherapies still fail in 10 to 40% of the infected patients and, in this scenario, targeted nanotherapeutics emerged as powerful allies for H. pylori eradication. Nano/microparticles conjugated with H. pylori binding molecules were developed to eliminate H. pylori by either (i) blocking essential mechanisms of infection, such as adhesion to gastric mucosa or (ii) binding and killing H. pylori through the release of drugs within the bacteria or at the site of infection. Glycan antigens (as Lewis B and sialyl-Lewis X), pectins, lectins, phosphatidylethanolamine and epithelial cell membranes were conjugated with nano/microparticles to successfully block H. pylori adhesion. Urea-coated nanoparticles were used to improve drug delivery inside bacteria through H. pylori UreI channel. Moreover, nanoparticles coated with antibodies against H. pylori and loaded with sono/photosensitizers, were promising for their application as targeted sono/photodynamic therapies. Further, non-specific H. pylori nano/microparticles, but only active in the acidic gastric environment, coated with binders to bacterial membrane, extracellular polymeric substances or to high temperature requirement A protease, were evaluated. In this review, an overview of the existing nanotherapeutics targeting H. pylori will be given and their rational, potential to counteract infection, as well as level of development will be presented and discussed.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"78"},"PeriodicalIF":9.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Variants of human DECTIN-1 rs16910526 are linked to differential reactive oxygen species production and susceptibility to tuberculosis. 人类 DECTIN-1 rs16910526 的变异与不同活性氧的产生和结核病的易感性有关。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2024-08-05 DOI: 10.1186/s12929-024-01067-w
Mónica Cufré, Mercedes Pastorini, Ignacio Martín, Rodrigo Failde, Domingo Palmero, Mercedes Alemán
{"title":"Variants of human DECTIN-1 rs16910526 are linked to differential reactive oxygen species production and susceptibility to tuberculosis.","authors":"Mónica Cufré, Mercedes Pastorini, Ignacio Martín, Rodrigo Failde, Domingo Palmero, Mercedes Alemán","doi":"10.1186/s12929-024-01067-w","DOIUrl":"10.1186/s12929-024-01067-w","url":null,"abstract":"<p><strong>Background: </strong>Dectin-1 is a transmembrane receptor that plays a pivotal role in recognising fungi and Mycobacterium tuberculosis (Mtb). A specific variant, DECTIN-1 rs16910526, results in a truncated receptor that disrupts membrane expression and ligand binding and is clinically associated with recurrent cutaneous mycoses. Previous research has clarified the role of Dectin-1 in boosting immune defenses against mycobacteria by enhancing reactive oxygen species (ROS) production in neutrophils (PMNs). Here, we investigated the association between the rs16910526 variant and Dectin-1 expression in PMNs, as well as intracellular ROS production in response to Mtb. Furthermore, we explored the potential link between the rs16910526 gene variant and TB outcomes in Argentina.</p><p><strong>Methods: </strong>DNA was extracted from blood samples obtained from a cohort of 178 TB patients and healthy subjects (HS) in Argentina. PCR amplification and sequencing were performed to identify the rs16910526 variant. Flow cytometry was utilised to assess Dectin-1 expression on the PMN plasma membrane and to measure intracellular ROS levels, as indicated by the oxidation of DHR123 in response to the Mtb antigen.</p><p><strong>Results: </strong>PMNs carrying the rs16910526 variant exhibited diminished Dectin-1 expression and ROS production in response to Mtb (p < 0.0001). In a case‒control study, the rs16910526 variant had an allelic frequency of 0.112 in TB patients and 0.051 in HS. Notably, 10 out of 88 HS and 18 out of 62 TB patients harboured the variant (odds ratio [OR]: 2.55 [95% CI 1.1-5.9, p = 0.03]), indicating a potential association with TB disease. Furthermore, TB patients with the rs16910526 variant exhibited a delayed sputum smear conversion time (p < 0.004) and 100% positivity for acid-fast bacilli smears (p < 0.00001).</p><p><strong>Conclusion: </strong>Our study identified a significant association between the SNP variant rs16910526 in the DECTIN-1 gene and Dectin-1 expression in the PMN, leading to altered ROS production. The higher frequency of this variant in TB patients compared to HS suggests a possible link with susceptibility to TB disease in Argentina.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"77"},"PeriodicalIF":9.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Retraction Note: Inhibitors of apoptosis proteins in experimental benign prostatic hyperplasia: effects of Serenoa repens, selenium and lycopene. 撤稿说明:实验性良性前列腺增生中的细胞凋亡蛋白抑制剂:蛇床子、硒和番茄红素的作用。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2024-08-02 DOI: 10.1186/s12929-024-01066-x
Letteria Minutoli, Domenica Altavilla, Herbert Marini, Mariagrazia Rinaldi, Natasha Irrera, Gabriele Pizzino, Alessandra Bitto, Salvatore Arena, Sebastiano Cimino, Francesco Squadrito, Giorgio Ivan Russo, Giuseppe Morgia
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