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The abiotic oxidation of As(III) is simultaneously mediated by the oxidation of Fe(II) in microaerobic environment, but the role of Fe minerals in the Fe(II)-mediated As(III) oxidation have been neglected. This work mimicked the microaerobic environment and examined the mechanisms of Fe(II) mediated the As(III) oxidation in the presence of Fe minerals using a variety of iron minerals (lepidocrocite, goethite, etc.). The results indicated the Fe(II) and As(III) oxidation rate were improved with Fe minerals, while As(III) oxidation efficiency increased by 1.3-1.8 times in comparison to that without minerals. Fe(II) mediated the As(III) oxidation happened on Fe minerals surface in the presence of Fe minerals. The As(III) oxidation efficiency increased with increasing Fe mineral concentrations (from 0.5 to 2 g L-1) but decreased with increasing pH values. Reactive oxygen species (ROS) that play a crucial role in As(III) oxidation were Fe(IV) and ·O2-, accounting for 42.7%-47.9% and 24.1%-29.8%, respectively. The Fe minerals facilitated the oxidation of As(III) by ROS and stimulated the release of ROS through the adsorbed-Fe(II) oxidation, both of which favored As(III) oxidation. This work highlighted the potential mechanisms of Fe minerals in promoting Fe(II) mediated the As(III) oxidation in microaerobic environment, especially in terms of As(III) oxidation efficiency, shedding a valuable insight on optimization of arsenic contaminated wastewater treatment processes.
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We recently revealed that activated STING is secreted into RAB22A-induced extracellular vesicles (R-EVs) and promotes antitumor immunity in cancer cells. Whether mesenchymal stem cell (MSC)-derived R-EVs containing activated STING can be used as a novel antitumor immunotherapy remains unclear, as MSC-derived EVs are promising cell-free therapeutics due to their superior biocompatibility and safety, as well as low immunogenicity. Here, we report that induced pluripotent stem cell (iPSC)-derived MSCs can generate R-EVs with a size and mechanism of formation that are similar to those of R-EVs produced from cancer cells. Furthermore, these MSC-derived R-EVs containing activated STING induced IFNß expression in recipient THP-1 monocytes and antitumor immunity in mice. Our findings reveal that the use of MSC-derived R-EVs containing activated STING is a promising cell-free strategy for antitumor immunity.
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Vesículas Extracelulares , Células Madre Pluripotentes Inducidas , Proteínas de la Membrana , Células Madre Mesenquimatosas , Animales , Células Madre Pluripotentes Inducidas/inmunología , Células Madre Pluripotentes Inducidas/metabolismo , Humanos , Células Madre Mesenquimatosas/inmunología , Células Madre Mesenquimatosas/metabolismo , Ratones , Proteínas de la Membrana/metabolismo , Vesículas Extracelulares/inmunología , Vesículas Extracelulares/metabolismo , Interferón beta/metabolismo , Interferón beta/inmunología , Células THP-1 , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/patología , Neoplasias/metabolismo , Línea Celular TumoralRESUMEN
Allergic asthma is a chronic non-communicable disease characterized by lung tissue inflammation. Current treatments can alleviate the clinical symptoms to some extent, but there is still no cure. Recently, the transplantation of mesenchymal stem cells (MSCs) has emerged as a potential approach for treating allergic asthma. Gingival-derived mesenchymal stem cells (GMSCs), a type of MSC recently studied, have shown significant therapeutic effects in various experimental models of autoimmune diseases. However, their application in allergic diseases has yet to be fully elucidated. In this study, using an OVA-induced allergic asthma model, we demonstrated that GMSCs decrease CD11b+CD11c+ proinflammatory dendritic cells (DCs), reduce Th2 cells differentiation, and thus effectively diminish eosinophils infiltration. We also identified that the core functional factor, hepatocyte growth factor (HGF) secreted by GMSCs, mediated its effects in relieving airway inflammation. Taken together, our findings indicate GMSCs as a potential therapy for allergic asthma and other related diseases.
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Type 17 helper T cells (Th17)-dominant neutrophilic airway inflammation is critical in the pathogenesis of steroid-resistant airway inflammation such as severe asthma. Small extracellular vesicles (sEV) derived from human mesenchymal stem cells (MSCs) display extensive therapeutic effects and advantages in many diseases. However, the role of MSC-sEV in Th17-dominant neutrophilic airway inflammation and the related mechanisms are still poorly studied. Here we found that MSC-sEV significantly alleviated the infiltration of inflammatory cells in peribronchial interstitial tissues and reduced levels of inflammatory cells, especially neutrophils, in bronchoalveolar lavage fluids (BALF) of mice with neutrophilic airway inflammation. Consistently, MSC-sEV significantly decreased levels of IL-17A in BALF and Th17 in lung tissues. Furthermore, we found that labelled MSC-sEV were taken up by human CD4+ T cells most obviously at 12 h after incubation, and distributed mostly in mouse lungs. More importantly, potential signaling pathways involved in the MSC-sEV mediated inhibition of Th17 polarization were found using RNA sequencing. Using Western blot, JAK2-STAT3 pathway was identified as an important role in the inhibition of Th17 polarization by MSC-sEV. We found that proteins in MSC-sEV were mostly involved in the therapeutic effects of MSC-sEV. In total, our study suggested that MSC-sEV could be a potential therapeutic strategy for the treatment of neutrophilic airway inflammation.
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Vesículas Extracelulares , Células Madre Mesenquimatosas , Neutrófilos , Factor de Transcripción STAT3 , Células Th17 , Células Th17/inmunología , Humanos , Animales , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/inmunología , Células Madre Mesenquimatosas/inmunología , Células Madre Mesenquimatosas/metabolismo , Ratones , Neutrófilos/inmunología , Factor de Transcripción STAT3/metabolismo , Janus Quinasa 2/metabolismo , Interleucina-17/metabolismo , Pulmón/inmunología , Pulmón/patología , Ratones Endogámicos C57BL , Células Cultivadas , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/citología , Asma/inmunología , Asma/terapia , Masculino , Transducción de Señal , Femenino , Modelos Animales de EnfermedadRESUMEN
Mesenchymal stem cells (MSCs) have demonstrated potent immunomodulatory properties that have shown promise in the treatment of autoimmune diseases, including rheumatoid arthritis (RA). However, the inherent heterogeneity of MSCs triggered conflicting therapeutic outcomes, raising safety concerns and limiting their clinical application. This study aimed to investigate the potential of extracellular vesicles derived from human gingival mesenchymal stem cells (GMSC-EVs) as a therapeutic strategy for RA. Through in vivo experiments using an experimental RA model, our results demonstrate that GMSC-EVs selectively homed to inflamed joints and recovered Treg and Th17 cell balance, resulting in the reduction of arthritis progression. Our investigations also uncovered miR-148a-3p as a critical contributor to the Treg/Th17 balance modulation via IKKB/NF-κB signaling orchestrated by GMSC-EVs, which was subsequently validated in a model of human xenograft versus host disease (xGvHD). Furthermore, we successfully developed a humanized animal model by utilizing synovial fibroblasts obtained from patients with RA (RASFs). We found that GMSC-EVs impeded the invasiveness of RASFs and minimized cartilage destruction, indicating their potential therapeutic efficacy in the context of patients with RA. Overall, the unique characteristics - including reduced immunogenicity, simplified administration, and inherent ability to target inflamed tissues - position GMSC-EVs as a viable alternative for RA and other autoimmune diseases.
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Artritis Reumatoide , Vesículas Extracelulares , Células Madre Mesenquimatosas , MicroARNs , FN-kappa B , Linfocitos T Reguladores , Células Th17 , Artritis Reumatoide/terapia , Artritis Reumatoide/inmunología , Artritis Reumatoide/metabolismo , Humanos , Animales , Células Th17/inmunología , Células Th17/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , FN-kappa B/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Ratones , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/inmunología , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/trasplante , Quinasa I-kappa B/metabolismo , Transducción de Señal , Modelos Animales de Enfermedad , Encía/citología , Encía/metabolismo , Encía/patología , Encía/inmunología , Masculino , Fibroblastos/metabolismoRESUMEN
Sulfur plays an essential role in agricultural production, but few studies have been reported on how sulfur simultaneously impacts the transformation of cadmium (Cd) and arsenic (As) in the soil-rice system. This research selected two soils co-contaminated with both Cd and As, varying in acidity and alkalinity levels, to study the impacts of elemental sulfur (S) and calcium sulfate (CaSO4) on the migration and accumulation of Cd and As by rice. Results indicated that two types of sulfur had a substantial (P < 0.05) impact on decreasing the contents of Cd (28.3-50.4 %) and As (20.1-38.6 %) in brown rice in acidic and alkaline soils. They also increased rice biomass (29.3-112.8 %) and reduced Cd transport coefficient (27.2-45.6 %) significantly (P < 0.05). Notably, sulfur augmented the generation of iron plaque on rice root surfaces, which increased the fixation of Cd (17.6-61.0 %) and As (14.0-45.9 %). SEM-EDS results also indicated that the rice root surface exhibited significant enrichment of Fe, Cd, and As. The mechanism of simultaneous Cd and As immobilization by sulfur application was mainly ascribed to the contribution of iron plaque. Additionally, sulfur reduced the contents of Cd and As in soil porewater and promoted the transformation of As(III) to As(V) to reduce the toxicity of As. The K-edge XAFS of As in iron plaque also confirmed that sulfur application significantly promoted As(III) oxidation. Sulfur also promoted the activities of antioxidant enzymes and the contents of NPT, GSH, and PCs in rice plants. In general, this study establishes a foundation for sulfur to lower As and Cd bioavailability in paddy soils, enhance iron plaque and rice resistance, and reduce heavy metal accumulation.
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Arsénico , Cadmio , Hierro , Oryza , Contaminantes del Suelo , Suelo , Azufre , Suelo/químicaRESUMEN
Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.
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Exosomas , Vesículas Extracelulares , Vesículas Extracelulares/metabolismo , Exosomas/metabolismo , Transporte Biológico , Biomarcadores/metabolismo , FenotipoRESUMEN
Alzheimer's disease (AD) is the most common neurodegenerative disease, with sporadic form being the predominant type. Neuroinflammation plays a critical role in accelerating pathogenic processes in AD. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEVs) regulate inflammatory responses and show great promise for treating AD. Induced pluripotent stem cell (iPSC)-derived MSCs are similar to MSCs and exhibit low immunogenicity and heterogeneity, making them promising cell sources for clinical applications. This study examined the anti-inflammatory effects of MSC-sEVs in a streptozotocin-induced sporadic mouse model of AD (sAD). The intracisternal administration of iPSC-MSC-sEVs alleviated NLRP3/GSDMD-mediated neuroinflammation, decreased amyloid deposition and neuronal apoptosis, and mitigated cognitive dysfunction. Furthermore, it explored the role of miR-223-3p in the iPSC-MSC-sEVs-mediated anti-inflammatory effects in vitro. miR-223-3p directly targeted NLRP3, whereas inhibiting miR-223-3p almost completely reversed the suppression of NLRP3 by MSC-sEVs, suggesting that miR-223-3p may, at least partially, account for MSC-sEVs-mediated anti-inflammation. Results obtained suggest that intracisternal administration of iPSC-MSC-sEVs can reduce cognitive impairment by inhibiting NLRP3/GSDMD neuroinflammation in a sAD mouse model. Therefore, the present study provides a proof-of-principle for applying iPSC-MSC-sEVs to target neuroinflammation in sAD.
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Enfermedad de Alzheimer , Modelos Animales de Enfermedad , Vesículas Extracelulares , Células Madre Mesenquimatosas , MicroARNs , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Ratones , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/metabolismo , Vesículas Extracelulares/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Inflamación/patología , Inflamación/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratones Endogámicos C57BL , MicroARNs/metabolismo , MicroARNs/genética , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/patología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismoRESUMEN
Abdominal Aortic Aneurysm (AAA) is a life-threatening vascular disease characterized by the weakening and ballooning of the abdominal aorta, which has no effective therapeutic approaches due to unclear molecular mechanisms. Using single-cell RNA sequencing, we analyzed the molecular profile of individual cells within control and AAA abdominal aortas. We found cellular heterogeneity, with increased plasmacytoid dendritic cells and reduced endothelial cells and vascular smooth muscle cells (VSMCs) in AAA. Up-regulated genes in AAA were associated with muscle tissue development and apoptosis. Genes controlling VSMCs aberrant switch from contractile to synthetic phenotype were significantly enriched in AAA. Additionally, VSMCs in AAA exhibited cell senescence and impaired oxidative phosphorylation. Similar observations were made in a mouse model of AAA induced by Angiotensin II, further affirming the relevance of our findings to human AAA. The concurrence of gene expression changes between human and mouse highlighted the impairment of oxidative phosphorylation as a potential target for intervention. Nicotinamide phosphoribosyltransferase (NAMPT, also named VISFATIN) signaling emerged as a signature event in AAA. NAMPT was significantly downregulated in AAA. NAMPT-extracellular vesicles (EVs) derived from mesenchymal stem cells restored NAMPT levels, and offered protection against AAA. Furthermore, NAMPT-EVs not only repressed injuries, such as cell senescence and DNA damage, but also rescued impairments of oxidative phosphorylation in both mouse and human AAA models, suggesting NAMPT supplementation as a potential therapeutic approach for AAA treatment. These findings shed light on the cellular heterogeneity and injuries in AAA, and offered promising therapeutic intervention for AAA treatment.
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Microbial anabolism and catabolism regulate the accumulation and dynamics of soil organic carbon (SOC). However, very little attention has been paid to the role of microbial functional traits in the accumulation and dynamics of SOC in forest soils. In this study, nine forest soils were selected at three altitudes (600 m, 1200 m, and 1500 m) and three soil depths (0-15 cm, 15-30 cm, and 30-45 cm) located in Jiugong Mountain. Vertical traits of functional genes encoding microbial carbohydrate-active enzymes (CAZymes) were observed using metagenomic sequencing. Soil amino sugars were used as biomarkers to indicate microbial residue carbon (MRC). The results showed that GH1 (ß-glucosidase: 147.49 TPM) and GH3 (ß-glucosidase: 109.09 TPM) were the dominant genes for plant residue decomposition, and their abundance increased with soil depth and peaked in the deep soil at 600 m (GH1: 147.89 TPM; GH3: 109.59 TPM). The highest abundance of CAZymes for fungal and bacterial residue decomposition were GH18 (chitinase: 30.81 TPM) and GH23 (lysozyme: 58.02 TPM), respectively. The abundance of GH18 increased with soil depth, while GH23 showed the opposite trend. Moreover, MRC accumulation was significantly positively correlated with CAZymes involved in the degradation of hemicellulose (r = 0.577, p = 0.002). Compared with the soil before incubation, MRC in the topsoil at the low and middle altitudes after incubation increased by 4 % and 8 %, respectively, while MRC in the soils at 1500 m tended to decrease (p > 0.05). The mineralization capacity of SOC at 1500 m was significantly higher than that at 1200 m and 600 m (p < 0.05). Our results suggested that microbial function for degrading plant residue components, especially hemicellulose and lignin, contributed greatly to SOC accumulation and dynamics. These results were vital for understanding the roles of microbial functional traits in C cycling in forest.
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Carbono , Celulasas , Carbono/química , Suelo/química , Microbiología del Suelo , Bosques , CarbohidratosRESUMEN
Although immunosuppressive drugs for targeting T cells are the standard of care in acute transplantation rejection, the role of innate immune cells should not be ignored. Here, single-cell RNA sequencing (scRNA-seq) and flow cytometry are performed to reveal the dynamic changes of innate immune cells within the acute rejection time and find a significantly-increased presence of Ly6G- Ly6C+ inflammatory macrophages and decreased presence of neutrophils among all types of immune cells. Next, to further explore potential targets regulating Ly6G- Ly6C+ inflammatory macrophages, scRNA-seq is used to analyze the reciprocal signaling of both neutrophils and macrophages, along with the surface genes of macrophages. It is found that activating colony-stimulating factor 1/ colony-stimulating factor 1 receptor (CSF1/CSF1R) andcluster of differentiation 47/signal regulatory protein α (CD47/SIRPα) signaling may serve as a strategy to relieve Ly6G- Ly6C+ inflammatory macrophage-mediated early graft rejection. To investigate this hypothesis, CSF1/CD47 dual-targeting nanovesicles (NVs) derived from IFN-γ-stimulated induced pluripotent stem cell-derived mesenchymal stem cells ( iPSC-MSCs )are designed and constructed. It is confirmed that CSF1/CD47 NVs synergistically induce the differentiation of Ly6G- Ly6C- M2 inhibitory macrophages by the CSF1/CSF1R pathway, and inhibit the phagocytosis of inflammatory macrophages and inflammatory response by the CD47/SIRPα pathway, ultimately relieving immune rejection. This study highlights the power of dual-targeting CSF1/CD47 NVs as an immunosuppressant against early innate immune responses with the potential for broad clinical applications.
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Trasplante de Corazón , Factor Estimulante de Colonias de Macrófagos , Factor Estimulante de Colonias de Macrófagos/genética , Antígeno CD47 , Fagocitosis , Inmunidad Innata , Perfilación de la Expresión GénicaRESUMEN
In arsenic (As)-contaminated paddy soil, microbial-driven nitrate (NO3-) reduction coupled with arsenite (As(III)) oxidation can reduce As toxicity, but the whereabouts of NO3- remain unclear. In this study, the experiments were established using selective streptomycin (STP) and cyclohexylamine to inhibit bacterial and fungal functional responses, respectively, and metagenomic sequencing techniques were used to explain the biological mechanisms of NO3- reduction coupled with As(III) oxidation in neutral As-contaminated paddy soil. The results indicated that fungal denitrification resulted in stronger nitrous oxide (N2O) emissions (321.6 µg kg-1) than bacterial denitrification (175.9 µg kg-1) in neutral As-contaminated paddy soil, but NO3- reduction coupled with As(III) oxidation reduced the N2O emissions. Only adding STP led to ammonium (NH4+) generation (17.7 mg kg-1), and simultaneously more NH4+ appeared in NO3- reduction coupled with As(III) oxidation; this may be because it improved the electron transfer efficiency by 18.2 %. Achromobacter was involved in denitrification coupled with As(III) oxidation. Burkholderiales was responsible for NO3- reduction to NH4+ coupled with As(III) oxidation. This study provided a theoretical basis for NO3- reduction coupled with As(III) oxidation reducing N2O emissions, promoting the reduction of NO3- to NH4+, and reducing As toxicity in paddy soil.
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Arsénico , Nitratos , Nitrógeno , Óxido Nitroso/análisis , Suelo , Bacterias , DesnitrificaciónRESUMEN
BACKGROUNDS: Allergic airway inflammation is prevalent worldwide and imposes a considerable burden on both society and affected individuals. This study aimed to investigate the therapeutic advantages of mesenchymal stem cells (MSCs) overexpressed interleukin-10 (IL-10) for the treatment of allergic airway inflammation, as both IL-10 and MSCs possess immunosuppressive properties. METHODS: Induced pluripotent stem cell (iPSC)-derived MSCs were engineered to overexpress IL-10 via lentiviral transfection (designated as IL-10-MSCs). MSCs and IL-10-MSCs were administered intravenously to mice with allergic inflammation induced by ovalbumin (OVA), and the features of allergic inflammation including inflammatory cell infiltration, Th cells in the lungs, and T helper 2 cell (Th2) cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. MSCs and IL-10-MSCs were co-cultured with CD4+ T cells from patients with allergic rhinitis (AR), and the levels of Th2 cells and corresponding type 2 cytokines were studied. RNA-sequence was performed to further investigate the potential effects of MSCs and IL-10-MSCs on CD4+ T cells. RESULTS: Stable IL-10-MSCs were established and characterised by high IL-10 expression. IL-10-MSCs significantly reduced inflammatory cell infiltration and epithelial goblet cell numbers in the lung tissues of mice with allergic airway inflammation. Inflammatory cell and cytokine levels in BALF also decreased after the administration of IL-10-MSCs. Moreover, IL-10-MSCs showed a stronger capacity to inhibit the levels of Th2 after co-cultured with CD4+ T cells from patients with AR. Furthermore, we elucidated lower levels of IL-5 and IL-13 in IL-10-MSCs treated CD4+ T cells, and blockade of IL-10 significantly reversed the inhibitory effects of IL-10-MSCs. We also reported the mRNA profiles of CD4+ T cells treated with IL-10-MSCs and MSCs, in which IL-10 played an important role. CONCLUSION: IL-10-MSCs showed positive effects in the treatment of allergic airway inflammation, providing solid support for the use of genetically engineered MSCs as a potential novel therapy for allergic airway inflammation.
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Células Madre Mesenquimatosas , Rinitis Alérgica , Animales , Humanos , Ratones , Líquido del Lavado Bronquioalveolar , Citocinas/metabolismo , Modelos Animales de Enfermedad , Inflamación/terapia , Inflamación/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Pulmón , Células Madre Mesenquimatosas/metabolismo , Ratones Endogámicos BALB C , OvalbúminaRESUMEN
Noise-induced hearing loss (NIHL) is one of the most prevalent acquired sensorineural hearing loss etiologies and is characterized by the loss of cochlear hair cells, synapses, and nerve terminals. Currently, there are no agents available for the treatment of NIHL because drug delivery to the inner ear is greatly limited by the blood-labyrinth barrier. In this study, we used mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) as nanoscale vehicles to deliver brain-derived neurotrophic factor (BDNF) and evaluated their protective effects in a mouse model of NIHL. Following intravenous administration, BDNF-loaded sEVs (BDNF-sEVs) efficiently increased the expression of BDNF protein in the cochlea. Systemic application of sEVs and BDNF-sEVs significantly attenuated noise-induced cochlear hair cell loss and NIHL in CBA/J mice. BDNF-sEVs also alleviated noise-induced loss of inner hair cell ribbon synapses and cochlear nerve terminals. In cochlear explants, sEVs and BDNF-sEVs effectively protected hair cells against H2O2-induced cell loss. Additionally, BDNF-sEVs remarkably ameliorated H2O2-induced oxidative stress, cell apoptosis, and cochlear nerve terminal degeneration. Transcriptomic analysis revealed that many mRNAs and miRNAs were involved in the protective actions of BDNF-sEVs against oxidative stress. Collectively, our findings reveal a novel therapeutic strategy of MSC-sEVs-mediated BDNF delivery for the treatment of NIHL.
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Vesículas Extracelulares , Pérdida Auditiva Provocada por Ruido , Animales , Ratones , Factor Neurotrófico Derivado del Encéfalo , Cóclea/metabolismo , Vesículas Extracelulares/metabolismo , Pérdida Auditiva Provocada por Ruido/tratamiento farmacológico , Pérdida Auditiva Provocada por Ruido/prevención & control , Peróxido de Hidrógeno/metabolismo , Ratones Endogámicos CBARESUMEN
There were limited researches on the scientific disposal of As-enriched plants, and how to reduce the available As content in the processed products and improve the utilization value were the key. In this study, the effect and mechanism of biochar produced by the As-enriched Pteris vittate before and after modification on the removal of As(III) in water were studied. The results indicated that the available As contents of Fe-BC300 and Fe-BC500 were reduced by 78.7 % and 91.9 % compared to original biochars, respectively. Modified biochars not only had a large adsorption capacity for As(III) (50.3 and 39.7 mg/g), but also can efficiently oxidize As(III) to As(V). The removal rate of As(III) by modified biochar was still higher than 50% after 3 cycles. The increase of the point of zero charge and the introduction of Fe were the main reasons for its efficient adsorption and oxidation of As(III).
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Arsénico , Contaminantes Químicos del Agua , Carbón Orgánico , Adsorción , Oxidación-ReducciónRESUMEN
Mesenchymal stromal cells (MSCs) have long been considered a potential tool for treatment of allergic inflammatory diseases, owing to their immunomodulatory characteristics. In recent decades, the medical utility of MSCs has been evaluated both in vitro and in vivo, providing a foundation for therapeutic applications. However, the existing limitations of MSC therapy indicate the necessity for novel therapies. Notably, small extracellular vesicles (sEV) derived from MSCs have emerged rapidly as candidates instead of their parental cells. The acquisition of abundant and scalable MSC-sEV is an obstacle for clinical applications. The potential application of MSC-sEV in allergic diseases has attracted increasing attention from researchers. By carrying biological microRNAs or active proteins, MSC-sEV can modulate the function of various innate and adaptive immune cells. In this review, we summarise the recent advances in the immunomodulatory properties of MSCs in allergic diseases, the cellular sources of MSC-sEV, and the methods for obtaining high-quality human MSC-sEV. In addition, we discuss the immunoregulatory capacity of MSCs and MSC-sEV for the treatment of asthma, atopic dermatitis, and allergic rhinitis, with a special emphasis on their immunoregulatory effects and the underlying mechanisms of immune cell modulation.
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Asma , Vesículas Extracelulares , Células Madre Mesenquimatosas , MicroARNs , Humanos , Vesículas Extracelulares/metabolismo , MicroARNs/metabolismo , Asma/terapia , Asma/metabolismo , InmunomodulaciónRESUMEN
As a good passivation agent for heavy metals, modified biochar has been widely used in environmental remediation. In order to explore the effects of different modification methods on arsenic (As) and cadmium (Cd) passivation in soil by biochar, this study used co-precipitation and impregnation pyrolysis to prepare iron-modified biochar. Through adsorption experiments and soil culture experiments, the properties of biochar, adsorption capacity, and the As and Cd passivation ability in soil were analyzed. The results showed that both modification methods could increase the iron (Fe) content and zero charge point of biochar, and the Fe minerals supported by Fe-modified biochar (FeBC-1) prepared by co-precipitation were mainly Fe3O4, FeO(OH), and γ-Fe2O3. The Fe-modified biochar (FeBC-2) prepared by impregnation pyrolysis mainly consisted of α-Fe2O3 and γ-Fe2O3. FeBC-1 showed strong adsorption and removal ability for As and Cd, with a removal rate of 21.40%-34.14%, which could significantly promote the conversion of non-obligate adsorbed As to residual As in soil, whereas FeBC-2 only had a good adsorption effect on As. The adsorption capacity of BC, FeBC-1, and FeBC-2 for Cd were proportional to their CEC. The adsorption and removal effect of BC on Cd was better than that of FeBC-1 and FeBC-2, which could significantly promote the conversion of soil acid-soluble Cd to stable residue Cd.
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Arsénico , Hierro , Cadmio , SueloRESUMEN
BACKGROUND: Mesenchymal stromal cells-derived small extracellular vesicles (MSC-sEVs) have recently attracted considerable attention because of their therapeutic potential in various immune diseases. We previously reported that MSC-sEVs could exert immunomodulatory roles in allergic airway inflammation by regulating group 2 innate lymphoid cell (ILC2) and dendritic cell (DC) functions. Therefore, this study aimed to investigate the indirect effects of MSC-sEVs on ILC2s from patients with allergic rhinitis (AR) via DCs. METHODS: Here, we isolated sEVs from induced pluripotent stem cells-MSCs using anion-exchange chromatography and mature DCs (mDCs) were treated with MSC-sEVs. sEV-mDCs were co-cultured with peripheral blood mononuclear cells from patients with AR or purified ILC2s. The levels of IL-13 and GATA3 in ILC2s were examined by flow cytometry. Bulk RNA sequence for mDCs and sEV-mDCs was employed to further probe the potential mechanisms, which were then validated in the co-culture systems. RESULTS: sEV-mDCs showed impaired capacity in priming the levels of IL-13 and GATA3 in ILC2s when compared with mDCs. Furthermore, there was higher PGE2 and IL-10 production from sEV-mDCs, and the blockade of them especially the former one reversed the inhibitory effects of sEV-mDCs. CONCLUSIONS: We demonstrated that MSC-sEVs were able to dampen the activating effects of mDCs on ILC2s in patients with AR. Mechanismly, the PGE2-EP2/4 axis played an essential role in the immunomodulatory effects of sEV-mDCs on ILC2s. Herein, we provided new insights into the mechanism underlying the therapeutic effects of MSC-sEVs in allergic airway inflammation.