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Journal of Controlled Release :... Aug 2023In an attempt to achieve antitumor effects by switching the phenotype of macrophages from the tumor-promoting M2 type to the tumor-suppressing M1 type, we fabricated...
In an attempt to achieve antitumor effects by switching the phenotype of macrophages from the tumor-promoting M2 type to the tumor-suppressing M1 type, we fabricated mannose-decorated/macrophage membrane-coated, silica-layered NaErF@NaLuF upconverting nanoparticles (UCNPs) co-doped with perfluorocarbon (PFC)/chlorin e6 (Ce6) and loaded with paclitaxel (PTX) (UCNP@mSiO-PFC/Ce6@RAW-Man/PTX: ∼61 nm; -11.6 mV). These nanoparticles were designed to have two major functionalities, (i) efficient singlet oxygen generation aided by an oxygen supply and (ii) good targeting to tumor-associated macrophage (TAMs) (M2-type), to induce polarization to M1 type macrophages that release proinflammatory cytokines and suppress breast cancers. The primary UCNPs consisted of lanthanide elements (erbium and lutetium) in a core@shell structure, and they facilely emitted 660 nm light in response to a deep-penetrating 808 nm near-infrared laser. Moreover, the UCNPs@mSiO-PFC/Ce6@RAW-Man/PTX were able to release O and generate O because of the co-doped PFC/Ce6 and upconversion. Our nanocarriers' excellent uptake to RAW 264.7 macrophage cells (M2 type) and efficient M1-type polarization activity were clearly demonstrated using qRT-PCR and immunofluorescence-based confocal laser scanning microscopy. Our nanocarriers displayed significant cytotoxicity to 4T1 cells in 2D culture and 3D co-culture systems of 4T1/RAW 264.7 cells. More importantly, UCNPs@mSiO-PFC/Ce6@RAW-Man/PTX (+808 nm laser) noticeably suppressed tumor growth in 4T1-xenografted mice, compared with the other treatment groups (332.4 vs. 709.5-1185.5 mm). We attribute this antitumor efficacy to the prominent M1-type macrophage polarization caused by our nanocarriers through efficient ROS/O generation and targeting of M2-type TAMs via mannose ligands on coated macrophage-membrane.
Topics: Animals; Mice; Mannose; Macrophages; Nanoparticles; Light; Photochemotherapy; Neoplasms; Paclitaxel; Cell Line, Tumor
PubMed: 37423526
DOI: 10.1016/j.jconrel.2023.07.009 -
Molecular & Cellular Proteomics : MCP Sep 2023The asialoglycoprotein receptor (ASGPR) and the mannose receptor C-type 1 (MRC1) are well known for their selective recognition and clearance of circulating...
The asialoglycoprotein receptor (ASGPR) and the mannose receptor C-type 1 (MRC1) are well known for their selective recognition and clearance of circulating glycoproteins. Terminal galactose and N-Acetylgalactosamine are recognized by ASGPR, while terminal mannose, fucose, and N-Acetylglucosamine are recognized by MRC1. The effects of ASGPR and MRC1 deficiency on the N-glycosylation of individual circulating proteins have been studied. However, the impact on the homeostasis of the major plasma glycoproteins is debated and their glycosylation has not been mapped with high molecular resolution in this context. Therefore, we evaluated the total plasma N-glycome and plasma proteome of ASGR1 and MRC1 deficient mice. ASGPR deficiency resulted in an increase in O-acetylation of sialic acids accompanied by higher levels of apolipoprotein D, haptoglobin, and vitronectin. MRC1 deficiency decreased fucosylation without affecting the abundance of the major circulating glycoproteins. Our findings confirm that concentrations and N-glycosylation of the major plasma proteins are tightly controlled and further suggest that glycan-binding receptors have redundancy, allowing compensation for the loss of one major clearance receptor.
Topics: Mice; Animals; Asialoglycoprotein Receptor; Mannose Receptor; Glycoproteins; Glycosylation; Protein Processing, Post-Translational; Carrier Proteins; Mannose
PubMed: 37414249
DOI: 10.1016/j.mcpro.2023.100615 -
Food Chemistry Sep 2024The wine market has always faced the problem of fraud, including the addition of exogenous sugar solutions to grape musts to increase the final alcohol content. Since in...
The wine market has always faced the problem of fraud, including the addition of exogenous sugar solutions to grape musts to increase the final alcohol content. Since in some countries the practice of chaptalization is prohibited (except by adding concentrated must) it is necessary to broaden the analytical techniques that allow the identification of this type of fraud. The aim of this study was to define an NMR-based sugar profile of genuine grape must to set concentration limits for each sugar as parameters of authenticity. Glucose, fructose, together with eleven minor sugars were quantified in 82 genuine Italian grape musts, developing an analytical procedure based on highly selective chemical shift filters followed by TOCSY. Alongside the characteristic myo- and scyllo-inositol, significant contents of mannose, galactose, and trehalose were also found. Otherwise, maltose, rhamnose, arabinose, sucrose and lactose are present in lower concentrations and show great concentration variability.
Topics: Vitis; Magnetic Resonance Spectroscopy; Wine; Sugars; Fruit
PubMed: 38657517
DOI: 10.1016/j.foodchem.2024.139374 -
Journal of Controlled Release :... Jun 2024In the pursuit of achieving better therapeutic outcomes in the treatment of HIV, innovative drug delivery strategies have been extensively explored. Mannose receptors,... (Review)
Review
In the pursuit of achieving better therapeutic outcomes in the treatment of HIV, innovative drug delivery strategies have been extensively explored. Mannose receptors, which are primarily found on macrophages and dendritic cells, offer promising targets for drug delivery due to their involvement in HIV pathogenesis. This review article comprehensively evaluates recent drug delivery system advancements targeting the mannose receptor. We have systematically described recent developments in creating and utilizing drug delivery platforms, including nanoparticles, liposomes, micelles, noisomes, dendrimers, and other nanocarrier systems targeted at the mannose receptor. These strategies aim to enhance drug delivery specificity, bioavailability, and therapeutic efficacy while decreasing off-target effects and systemic toxicity. Furthermore, the article delves into how mannose receptors and HIV interact, highlighting the potential for exploiting this interaction to enhance drug delivery to infected cells. The review covers essential topics, such as the rational design of nanocarriers for mannose receptor recognition, the impact of physicochemical properties on drug delivery performance, and how targeted delivery affects the pharmacokinetics and pharmacodynamics of anti-HIV agents. The challenges of these novel strategies, including immunogenicity, stability, and scalability, and future research directions in this rapidly growing area are discussed. The knowledge synthesis presented in this review underscores the potential of mannose receptor-based targeted drug delivery as a promising avenue for advancing HIV treatment. By leveraging the unique properties of mannose receptors, researchers can design drug delivery systems that cater to individual needs, overcome existing limitations, and create more effective and patient-friendly treatments in the ongoing fight against HIV/AIDS.
PubMed: 38849091
DOI: 10.1016/j.jconrel.2024.06.002 -
International Journal of Biological... Jul 2023Biotic and abiotic stresses impose adverse effects on plant's development, growth, and production. For the past many years, researchers are trying to understand the... (Review)
Review
Biotic and abiotic stresses impose adverse effects on plant's development, growth, and production. For the past many years, researchers are trying to understand the stress induced responses in plants and decipher strategies to produce stress tolerant crops. It has been demonstrated that molecular networks encompassing an array of genes and functional proteins play a key role in generating responses to combat different stresses. Newly, there has been a resurgence of interest to explore the role of lectins in modulating various biological responses in plants. Lectins are naturally occurring proteins that form reversible linkages with their respective glycoconjugates. To date, several plant lectins have been recognized and functionally characterized. However, their involvement in stress tolerance is yet to be comprehensively analyzed in greater detail. The availability of biological resources, modern experimental tools, and assay systems has provided a fresh impetus for plant lectin research. Against this backdrop, the present review provides background information on plant lectins and recent knowledge on their crosstalks with other regulatory mechanisms, which play a remarkable role in plant stress amelioration. It also highlights their versatile role and suggests that adding more information to this under-explored area will usher in a new era of crop improvement.
Topics: Plant Lectins; Stress, Physiological; Crops, Agricultural
PubMed: 37301347
DOI: 10.1016/j.ijbiomac.2023.125272 -
Journal of Nanobiotechnology Nov 2023The implementation of pyroptosis exhibits significant potential as a tactic to enhance tumor immune microenvironments. Previous applications of pyroptosis inducers have...
BACKGROUND
The implementation of pyroptosis exhibits significant potential as a tactic to enhance tumor immune microenvironments. Previous applications of pyroptosis inducers have encountered various limitations, such as the development of drug resistance, manifestation of toxic side effects, and a deficiency in targeting capabilities. As a result, there is a growing demand for tumor therapeutic molecules that can overcome these obstacles. Therefore, the objective of this study is to develop a multifunctional nanospheres that addresses these challenges by enabling high-precision targeting of tumor cells and inducing effective pyroptosis.
RESULTS
We prepared a mannose-modified MOF called mannose-doped FeO@NH-MIL-100 (M-FNM). M-FNM could enter CAL27 cells through MR-mediated endocytosis, which caused in a significant increase in the level of intracellular ROS. This increase subsequently triggered ER stress and activated the PERK-eIF2α-ATF4-CHOP signaling pathway. CHOP then mediated the downstream cascade of Caspase-1, inducing pyroptosis. In in vivo experiments, M-FNM demonstrated excellent targeting ability and exhibited anti-tumor effects. Additionally, M-FNM reshaped the immune microenvironment by promoting the infiltration of anti-tumor immune cells, primarily T lymphocytes.
CONCLUSIONS
M-FNM significantly decreased tumor growth. This novel approach to induce pyroptosis in tumor cells using M-FNM may offer new avenues for the development of effective immunotherapies against cancer.
Topics: Humans; Pyroptosis; Apoptosis; Mannose; Metal-Organic Frameworks; Endoplasmic Reticulum Stress; eIF-2 Kinase; Neoplasms; Tumor Microenvironment
PubMed: 37968665
DOI: 10.1186/s12951-023-02175-9 -
Molecular Immunology Oct 2023Vacuolar-type H-ATPase (V-ATPase) critically controls phagosome acidification to promote pathogen digestion and clearance in macrophage. However, the specific subunits...
Vacuolar-type H-ATPase (V-ATPase) critically controls phagosome acidification to promote pathogen digestion and clearance in macrophage. However, the specific subunits of V-ATPase have been evidenced to play contradictory functions in inflammatory cytokines generation and secretion exposure to external bacterial or LPS stimulation. Therefore, identifying the unique function of the separate subunit of V-ATPase is extremely important to regulate macrophage function. Here, we found that D-mannose, a C-2 epimer of glucose, suppressed ATP6V1B2 lysosomal translocation to inhibit V-ATPase activity in macrophages, thereby causing the scaffold protein axis inhibitor protein (AXIN) recruitment to lysosomal membrane and AMPK activation. Correspondingly, LPS-stimulated macrophage M1 polarization was significantly suppressed by D-mannose via down-regulating NF-κB signaling pathway in response to AMPK activation, while IL-4 induced macrophage M2 polarization were not affected. Furthermore, the failure of lysosomal localization of ATP6V1B2 caused by D-mannose also led to the acidification defects of lysosome. Therefore, D-mannose displayed a remarkable function in inhibiting macrophage phagocytosis and bacterial killing. Taken together, D-mannose acts a novel V-ATPase suppressor to attenuate macrophage inflammatory production but simultaneously prevent macrophage phagocytosis and bacterial killing.
Topics: Adenosine Triphosphatases; Cytokines; Mannose; AMP-Activated Protein Kinases; Lipopolysaccharides; Macrophages
PubMed: 37660434
DOI: 10.1016/j.molimm.2023.08.013 -
Current Drug Delivery Jan 2024Mannose, an isomer of glucose, exhibits a distinct molecular structure with the same formula but a different atom arrangement, contributing to its specific biological...
Mannose, an isomer of glucose, exhibits a distinct molecular structure with the same formula but a different atom arrangement, contributing to its specific biological functions. Widely distributed in body fluids and tissues, particularly in the nervous system, skin, testes, and retinas, mannose plays a crucial role as a direct precursor for glycoprotein synthesis. Glycoproteins, essential for immune regulation and glycosylation processes, underscore the significance of mannose in these physiological activities. The clinical and biomedical applications of mannose are diverse, encompassing its anti-inflammatory properties, potential to inhibit bacterial infections, role in metabolism regulation, and suggested involvement in alleviating diabetes and obesity. Additionally, mannose shows promise in antitumor effects, immune modulation, and the construction of drug carriers, indicating a broad spectrum of therapeutic potential. The article aims to present a comprehensive review of mannose, focusing on its molecular structure, metabolic pathways, and clinical and biomedical applications, and also to emphasize its status as a promising therapeutic agent.
PubMed: 38310442
DOI: 10.2174/0115672018275954231220101637 -
Nutrients Aug 2023Urinary tract infections represent a common and significant health concern worldwide. The high rate of recurrence and the increasing antibiotic resistance of... (Review)
Review
Urinary tract infections represent a common and significant health concern worldwide. The high rate of recurrence and the increasing antibiotic resistance of uropathogens are further worsening the current scenario. Nevertheless, novel key ingredients such as D-mannose, chondroitin sulphate, hyaluronic acid, and -acetylcysteine could represent an important alternative or adjuvant to the prevention and treatment strategies of urinary tract infections. Several studies have indeed evaluated the efficacy and the potential use of these compounds in urinary tract health. In this review, we aimed to summarize the characteristics, the role, and the application of the previously reported compounds, alone and in combination, in urinary tract health, focusing on their potential role in urinary tract infections.
Topics: Humans; Hyaluronic Acid; Acetylcysteine; Chondroitin Sulfates; Mannose; Urinary Tract Infections; Urinary Tract
PubMed: 37630763
DOI: 10.3390/nu15163573 -
PLoS Pathogens Sep 2023The covalent modification of bacterial (lipo)polysaccharides with discrete substituents may impact their biosynthesis, export and/or biological activity. Whether...
The covalent modification of bacterial (lipo)polysaccharides with discrete substituents may impact their biosynthesis, export and/or biological activity. Whether mycobacteria use a similar strategy to control the biogenesis of its cell envelope polysaccharides and modulate their interaction with the host during infection is unknown despite the report of a number of tailoring substituents modifying the structure of these glycans. Here, we show that discrete succinyl substituents strategically positioned on Mycobacterium tuberculosis (Mtb) lipoarabinomannan govern the mannose-capping of this lipoglycan and, thus, much of the biological activity of the entire molecule. We further show that the absence of succinyl substituents on the two main cell envelope glycans of Mtb, arabinogalactan and lipoarabinomannan, leads to a significant increase of pro-inflammatory cytokines and chemokines in infected murine and human macrophages. Collectively, our results validate polysaccharide succinylation as a critical mechanism by which Mtb controls inflammation.
Topics: Humans; Animals; Mice; Lipopolysaccharides; Mannose; Tuberculosis; Inflammation
PubMed: 37669276
DOI: 10.1371/journal.ppat.1011636