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1.
Synth Syst Biotechnol ; 9(3): 586-593, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38720820

RESUMO

Halomonas bluephagenesis TD serves as an exceptional chassis for next generation industrial biotechnology to produce various products. However, the simultaneous editing of multiple loci in H. bluephagenesis TD remains a significant challenge. Herein, we report the development of a multiple loci genome editing system, named CRISPR-deaminase-assisted base editor (CRISPR-BE) in H. bluephagenesis TD. This system comprises two components: a cytidine (CRISPR-cBE) and an adenosine (CRISPR-aBE) deaminase-based base editor. CRISPR-cBE can introduce a cytidine to thymidine mutation with an efficiency of up to 100 % within a 7-nt editing window in H. bluephagenesis TD. Similarly, CRISPR-aBE demonstrates an efficiency of up to 100 % in converting adenosine to guanosine mutation within a 7-nt editing window. CRISPR-cBE has been further validated and successfully employed for simultaneous multiplexed editing in H. bluephagenesis TD. Our findings reveal that CRISPR-cBE efficiently inactivated all six copies of the IS1086 gene simultaneously by introducing stop codon. This system achieved an editing efficiency of 100 % and 41.67 % in inactivating two genes and three genes, respectively. By substituting the Pcas promoter with the inducible promoter PMmp1, we optimized CRISPR-cBE system and ultimately achieved 100 % editing efficiency in inactivating three genes. In conclusion, our research offers a robust and efficient method for concurrently modifying multiple loci in H. bluephagenesis TD, opening up vast possibilities for industrial applications in the future.

2.
J Hepatocell Carcinoma ; 11: 767-774, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38689801

RESUMO

Objective: To explore the distribution of probable causes and clinical characteristics of non-B and non-C (NBNC) primary liver cancer (PLC) patients in the HBV-endemic region. Methods: A total of 86 individuals with biopsy-proven NBNC-PLC were enrolled. NBNC-PLC patients were defined as negative for both anti-HCV antibodies and five serum hepatitis B markers. Patients' characteristics were collected from medical records. Results: Among them, most of the NBNC-PLC patients had intrahepatic cholangiocarcinoma (ICC) (81.4%), and 12.8% had hepatocellular carcinoma (HCC). The NBNC ICC group had more platelet count, GGT, and CA199 levels; approximately two-thirds were female, and it was more often present in patients with biliary inflammatory diseases, especially intrahepatic biliary lithiasis. The NBNC HCC group was older and had a higher proportion of dyslipidemia, obesity, cirrhosis, and AFP levels. Conclusion: Our data revealed that most of the NBNC PLC patients were ICC. Female patients with biliary inflammatory diseases and higher CA199 levels had an increased risk of ICC, and patients with metabolic risk factors and elevated AFP levels were more likely to develop HCC. Additional research should be performed to verify this finding.

3.
Int J Nanomedicine ; 19: 4007-4019, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38715701

RESUMO

Introduction: Nanosized outer membrane vesicles (OMVs) from Gram-negative bacteria have attracted increasing interest because of their antitumor activity. However, the antitumor effects of MVs isolated from Gram-positive bacteria have rarely been investigated. Methods: MVs of Staphylococcus aureus USA300 were prepared and their antitumor efficacy was evaluated using tumor-bearing mouse models. A gene knock-in assay was performed to generate luciferase Antares2-MVs for bioluminescent detection. Cell counting kit-8 and lactic dehydrogenase release assays were used to detect the toxicity of the MVs against tumor cells in vitro. Active caspase-1 and gasdermin D (GSDMD) levels were determined using Western blot, and the tumor inhibition ability of MVs was determined in B16F10 cells treated with a caspase-1 inhibitor. Results: The vesicular particles of S. aureus USA300 MVs were 55.23 ± 8.17 nm in diameter, and 5 µg of MVs remarkably inhibited the growth of B16F10 melanoma in C57BL/6 mice and CT26 colon adenocarcinoma in BALB/c mice. The bioluminescent signals correlated well with the concentrations of the engineered Antares2-MVs (R2 = 0.999), and the sensitivity for bioluminescence imaging was 4 × 10-3 µg. Antares2-MVs can directly target tumor tissues in vivo, and 20 µg/mL Antares2-MVs considerably reduced the growth of B16F10 and CT26 tumor cells, but not non-carcinomatous bEnd.3 cells. MV treatment substantially increased the level of active caspase-1, which processes GSDMD to trigger pyroptosis in tumor cells. Blocking caspase-1 activation with VX-765 significantly protected tumor cells from MV killing in vitro and in vivo. Conclusion: S. aureus MVs can kill tumor cells by activating the pyroptosis pathway, and the induction of pyroptosis in tumor cells is a promising strategy for cancer treatment.


Assuntos
Caspase 1 , Piroptose , Staphylococcus aureus , Animais , Feminino , Camundongos , Antineoplásicos , Membrana Externa Bacteriana , Caspase 1/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo , Melanoma Experimental/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Proteínas de Ligação a Fosfato/metabolismo , Staphylococcus aureus/metabolismo
4.
Blood ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635762

RESUMO

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting the use of axi-cel in patients with LBCL, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings. In the real-world setting, 1290 patients with R/R LBCL who received axi-cel between 2017-2020 were identified from the Center for International Blood and Marrow Transplant Research database; 106 and 169 patients were included from the ZUMA-1 and ZUMA-7 clinical trials, respectively. Adjusted odds ratio (OR) and hazard ratio (HR) for race and ethnicity groups are reported. Overall survival was consistent across race/ethnicity groups. However, non-Hispanic (NH) Black patients had lower overall response rate (OR, 0.37, [95% CI, 0.22-0.63]) and lower complete response rate (OR, 0.57, [95% CI, 0.33-0.97]) than NH-white patients. NH-Black patients also had a shorter progression-free survival versus NH-white (HR, 1.41, [95% CI, 1.04-1.90]) and NH-Asian patients (HR, 1.67, [95% CI, 1.08-2.59]). NH-Asian patients had a longer duration of response compared with NH-white (HR, 0.56, [95% CI, 0.33-0.94]) and Hispanic patients (HR, 0.54, [95% CI, 0.30-0.97]). There was no difference in cytokine release syndrome by race/ethnicity; however, higher rates of any-grade ICANS were observed in NH-white patients compared with other patients. These results provide important context when treating patients with R/R LBCL with axi-cel across different racial and ethnic groups. ZUMA-1 (NCT02348216) and ZUMA-7 (NCT03391466), both registered on ClinicalTrials.gov.

5.
Nano Lett ; 24(18): 5662-5668, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38682870

RESUMO

The sensitivity of triboelectric nanogenerators (TENGs) to the surface charge density highlights the significance of triboelectric materials and their modifications. Efforts have been directed toward developing effective strategies for increasing the surface charge density, expanding the potential applications of TENGs. This study proposes the use of irradiation technology for grafting to modify the electron-donating capability of poly(ether sulfone) (PES), thereby affording a dual benefit of enhancing the surface charge density and inducing a shift in the position of PES from negative to positive within the triboelectric series. The TENG based on grafted PES has resulted in a significant 3-fold increase in surface charge density compared to that of pristine PES, reaching 263 µC m-2. The surface charge density can be further increased to 502 µC m-2 through charge pumping. Notably, irradiation technology presents advantages over chemical grafting methods, particularly in terms of sustainability and environmental friendliness. This innovative approach shows great potential in advancing the domain of TENGs.

6.
Blood Adv ; 2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662645

RESUMO

Chimeric antigen receptor (CAR) T-cell therapies have revolutionized the treatment of hematological cancers. Production requires a complex logistical process from leukapheresis to patient infusion, the vein-to-vein time (V2VT), during which a patients clinical condition may deteriorate. This study was designed to estimate the benefits of reduced V2VT for third-line+ (3L+) relapsed/refractory large B-cell lymphoma (r/r LBCL) patients treated with CAR T. A mathematical model was developed to estimate the lifetime outcomes of a hypothetical cohort of patients who had either a 'long' or 'short' V2VT. Life-years (LYs), quality-adjusted life years (QALYs), and costs were estimated. Scenario analyses were performed to assess the robustness of results to key assumptions.  The results of the model show that reducing V2VT from 54 days (tisa-cel median V2VT; JULIET) to 24 days (axi-cel median V2VT; ZUMA-1) led to a 3.2-year gain in life expectancy (4.2 vs 7.7 LYs), and 2.4 additional QALYs (3.2 vs 5.6) per patient. Furthermore, a shorter V2VT was shown to be cost-effective under conventional willingness-to-pay thresholds in the United States. Results are driven by a higher infusion rate and and a better efficacy of CAR T-cell therapy for those infused. Scenario analyses using a smaller difference in V2VT (24 vs 36 days) produced consistent results. Our study is the first to quantify lifetime V2VT-related outcomes for 3L+ r/r LBCL patients treated with CAR T utilizing currently available evidence. Shorter V2VTs led to improved outcomes, demonstrating the importance of timely infusion achievable by faster manufacturing times and optimization of hospital delivery.

7.
Front Immunol ; 15: 1306059, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524123

RESUMO

Background: There is a growing acknowledgment of the potential influence of antioxidative effects resulting from dietary decisions on the occurrence of stroke. The objective of this study was to elucidate the correlation between the composite dietary antioxidant index (CDAI) and the incidence of stroke in the general population of the United States. Methods: We gathered cross-sectional data encompassing 40,320 participants from the National Health and Nutrition Examination Survey (NHANES) spanning the years 1999 to 2018. Employing weighted multivariate logistic regression, we assessed the correlation between CDAI and stroke, while also investigating potential nonlinear relationships through restricted cubic spline (RCS) regression. Further, the intake of CDAI components were then incorporated into a predictive nomogram model, subsequently evaluated for its discriminatory prowess in stroke risk assessment using the receiver operating characteristic (ROC) curve. Results: Post-adjustment for confounding variables, we found that higher CDAI score were associated with a decreased risk of stroke, the odds ratio (OR) [95% CI] of CDAI associating with prevalence was 0.96 [0.94-0.98] (P< 0.001). Moreover, the adjusted OR [95% CI] for stroke across ascending CDAI quartiles stood at 0.90 [0.74-1.09], 0.74 [0.60-0.91], and 0.61 [0.50-0.76] compared to the reference quartile, respectively. The RCS analysis indicated a nonlinear yet negative correlation between CDAI and stroke. The nomogram model, constructed based the intake of antioxidants, exhibited a significant predictive capacity for stroke risk, boasting an area under the curve (AUC) of 77.4% (76.3%-78.5%). Conclusion: Our investigation ascertained a nonlinear negative relationship between CDAI and stroke within the broader American population. However, given the inherent limitations of the cross-sectional design, further comprehensive research is imperative to establish the causative nature of this association.


Assuntos
Antioxidantes , Acidente Vascular Cerebral , Humanos , Prevalência , Estudos Transversais , Inquéritos Nutricionais , Acidente Vascular Cerebral/epidemiologia
8.
Environ Sci Pollut Res Int ; 31(18): 26665-26674, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38451459

RESUMO

Carbon source addition is an important way improving the carbon and nitrogen transformation in aquaculture system; however, its effectiveness of algal-bacterial-based aquaponics (AA) through carbon source addition is still vague. In this study, the influences of organic carbon (OC-AA system) and inorganic carbon (IC-AA system) addition and without carbon source addition (C-AA system) on the operational performance of AA system were investigated. Results showed that 10.1-19.5% increase of algal-bacterial biomass enhanced the purifying effect of ammonia nitrogen in OC-AA system and IC-AA system relative to C-AA system. Moreover, extra electron donor supply in the OC-AA system obtained the lowest NO3--N concentration. However, that was at the cost of aggravated N2O conversion ratio, which increased by more than 2.0-folds than other systems, attributing to 2.9-folds increase of nirS gene abundance. In addition, carbon source addition increased the pH and then decreased the fish biomass production of AA system. The results of this study would provide theoretical supports of carbon source addition on the performance of nutrient transformation and greenhouse gas effect in AA system.


Assuntos
Aquicultura , Carbono , Gases de Efeito Estufa , Qualidade da Água , Nitrogênio , Biomassa , Bactérias/metabolismo
9.
Am J Hematol ; 99(5): 880-889, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38504387

RESUMO

Axicabtagene ciloleucel (axi-cel) in trials has demonstrated favorable efficacy compared with historical controls after ≥2 lines of therapy for the treatment of relapsed or refractory (R/R) large B cell lymphoma (LBCL). Herein, we compared the real-world effectiveness of axi-cel with efficacy and effectiveness of chemoimmunotherapy (CIT) in patients aged ≥65 years and patients with Eastern Cooperative Oncology Group performance status (ECOG PS) of 2. A total of 1146 patients treated with commercial axi-cel for R/R LBCL with ≥2 lines of prior therapy were included from the Center for International Blood and Marrow Transplantation Research prospective observational study, and 469 patients treated with CIT for R/R LBCL after ≥2 lines of prior therapy were included from SCHOLAR-1 (an international, multicohort, retrospective study). After propensity score matching, at a median follow-up of 24 months for patients receiving axi-cel and 60 months for patients receiving CIT, 12-month overall survival rates were 62% and 28%, respectively (hazard ratio, 0.30 [95% CI, 0.24-0.37]). Objective response rate (ORR) was 76% (complete response [CR] rate 58%) in patients receiving axi-cel versus 28% (CR rate 16%) for those receiving CIT. A 57% difference in ORR (55% difference in CR rate) favoring axi-cel over CIT was observed among patients aged ≥65 years. Increased magnitude of benefit in response rates for axi-cel versus CIT was also observed among patients with ECOG PS = 2. These findings further support the broader use of axi-cel in older patients and patients with ECOG PS = 2 with R/R LBCL.


Assuntos
Produtos Biológicos , Linfoma Difuso de Grandes Células B , Humanos , Idoso , Estudos Retrospectivos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Resposta Patológica Completa , Imunoterapia Adotiva , Antígenos CD19
10.
Water Res ; 253: 121348, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38401472

RESUMO

Manganese oxide (MnOx) is receiving increased interest in the nutrient removal of constructed wetlands (CWs); however, its service effectiveness for simultaneous greenhouse gas (GHG) emissions reduction is still vague. In this study, three vertical flow CWs, i.e., volcanics (CCW), manganese sand uniformly mixing with volcanics (Mn-CW) and MnOx doped volcanics (MnV-CW), were constructed to investigate the underlying mechanisms of MnOx on nutrient removal enhancement and greenhouse gas (GHG) emissions reduction. The results showed that the MnOx doped volcanics optimized the oxidation-reduction potential surrounding the substrate (-164.0 ∼ +141.1 mv), and resulted in the lowest GHG emissions (CO2-equivalent) from MnV-CW, 16.8-36.5 % lower than that of Mn-CW and CCW. This was mainly ascribed to mitigation of N2O produced during the NO3--N reduction process, according to results of 15N stable isotope labeling. Analysis of the microbial community structure revealed that due to the optimized redox conditions through chemical doping of MnOx on volcanics, the abundance of microbe involved in denitrification and Mn-oxidizing process in the MnV-CW was significantly increased at genus level, which led to a higher Mn cycling efficiency between biogenic MnOx and Mn2+, and enhanced denitrification efficiency and N2O emission reduction. This study would help to understand and provide a preferable reference for future applications for manganese-based CW.


Assuntos
Gases de Efeito Estufa , Compostos de Manganês , Manganês , Óxidos , Áreas Alagadas , Nitrogênio , Oxirredução , Desnitrificação
11.
Medicine (Baltimore) ; 103(7): e36593, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363942

RESUMO

Doxorubicin (DOX) is one of the most effective chemotherapeutic agents. However, the nonselective effect leads to serious cardiotoxicity risk in clinical use. Curcumin is a well-known dietary polyphenol that showed a protective effect against the cardiotoxic effect of DOX. This study aimed to assess the role of curcumin in protection against DOX-induced cardiotoxicity. Potential compound and disease targets were obtained from relevant databases, and common targets were screened. Protein-protein interaction (PPI) was used to predict the core targets. Gene ontology (GO) bioprocess analysis and Kyoto encyclopedia of genes and genome enrichment analysis enriched the possible biological processes (BP), cellular components, molecular function, and signaling pathways involved. Finally, the binding of curcumin to target proteins was evaluated through molecular docking. The docking score verified the reliability of the prediction results. In total, 205 curcumin and 700 disease targets were identified. A topological analysis of the PPI network revealed 10 core targets including TP53, tumor necrosis factor-alpha (TNF), AKT1, vascular endothelial growth factor A (VEGFA), prostaglandin-endoperoxide synthase 2 (PTGS2), signal transducer and activator of the transcription 3 (STAT3), HIF1A, MYC, epidermal growth factor receptor (EGFR), and CASP3 (Caspase-3). Furthermore, the enrichment analyses indicated that the effects of curcumin were mediated by genes related to oxidation, inflammation, toxification, cell proliferation, migration, apoptosis, wounding, metabolism, proteolysis, and the signaling pathway of calcium (Ca2+). Molecular docking showed that curcumin could bind with the target proteins with strong molecular force, exhibiting good docking activity. Curcumin has a multi-cardioprotective effect by modulating the core targets' expression in DOX-induced cardiotoxicity. This study elucidated the key target proteins and provided a theoretical basis for further exploring curcumin in the prevention and treatment of DOX-induced cardiotoxicity.


Assuntos
Curcumina , Medicamentos de Ervas Chinesas , Humanos , Simulação de Acoplamento Molecular , Curcumina/farmacologia , Curcumina/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Farmacologia em Rede , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Reprodutibilidade dos Testes
12.
bioRxiv ; 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38328117

RESUMO

Neuroblastoma is a leading cause of death in childhood cancer cases. Unlike adult malignancies, which typically develop from aged cells through accumulated damage and mutagenesis, neuroblastoma originates from neural crest cells with disrupted differentiation. This distinct feature provides novel therapeutic opportunities beyond conventional cytotoxic methods. Previously, we reported that the mitochondrial uncoupler NEN (niclosamide ethanolamine) activated mitochondria respiration to reprogram the epigenome, promoting neuronal differentiation. In the current study, we further combine NEN with retinoic acid (RA) to promote neural differentiation both in vitro and in vivo. The treatment increased the expression of RA signaling and neuron differentiation-related genes, resulting in a global shift in the transcriptome towards a more favorable prognosis. Overall, these results suggest that the combination of a mitochondrial uncoupler and the differentiation agent RA is a promising therapeutic strategy for neuroblastoma.

14.
Sci Total Environ ; 917: 170526, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38286296

RESUMO

The use of iron-manganese oxide (FMO) as a promising amendment for remediating arsenic (As) contamination in soils has gained attention, but its application is limited owing to agglomeration issues. This study aims to address agglomeration using surfactant-modified FMO and investigate their stabilization behavior towards As and resulting environmental changes upon amendments. The results confirmed the efficacy of surfactants and demonstrated that cetyltrimethylammonium-bromide-modified FMO significantly reduced the leaching concentration of As by 92.5 % and effectively suppressed the uptake of As by 85.8 % compared with the control groups. The ratio of the residual fraction increased from 30.5-41.6 % in unamended soil to 67.9-69.2 %. The number of active sites was through the introduction of surfactants and immobilized As via complexation, ion exchange, and redox reactions. The study also revealed that amendments and the concentration of As influenced the soil physicochemical properties and enriched bacteria associated with As and Fe reduction and changed the distribution of C, N, Fe, and As metabolism genes, which promoted the stabilization of As. The interactions among cetyltrimethylammonium bromide, FMO, and microorganisms were found to have the greatest effect on As immobilization.

16.
ACS Omega ; 8(50): 48104-48112, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38144079

RESUMO

Iron (Fe)-loaded biochar has garnered attention for its potential applications in recent years. However, the pyrolysis process of Fe-loaded biochar generates polycyclic aromatic hydrocarbons (PAHs), which can have adverse effects on both human health and the environment. This study explored the correlation between Fe loading and PAH production in Fe-loaded biochar. The results indicate that increasing Fe loading in biochar reduces the PAH concentration, with the most significant decrease observed in naphthalene (0.02-0.08 mg/kg). This reduction can be attributed to the decrease in precursor compounds (e.g., C2H2), substitution of the C=O bond by Fe-O, and a decrease in the dissolved organic matter concentration (3.19-10.76 mg/L) with Fe loading. When Fe loading increased from 0 to 10%, the ecological toxicity of biochar increased by 33.48% due to an elevated production of dibenzo[a,h]anthracene, which poses a significant risk to human health. Therefore, it is imperative to take into consideration the ecological risk of PAHs prior to the application of Fe-loaded biochar. This study presents a comprehensive risk assessment of Fe-loaded biochar and provides valuable insights into the optimization of its production and safe application.

17.
Int Immunopharmacol ; 124(Pt B): 111003, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37806104

RESUMO

BACKGROUND: Allergic rhinitis (AR) is a worldwide problem that affects people of all ages, impairing patients' physical and mental health and causing great social expenditure. Animal studies have suggested the potential efficacy of mesenchymal stem cell (MSC) therapy in treating AR. Our meta-analysis was performed to evaluate the effect of MSC therapy in animal models of AR by pooling animal studies. METHODS: The search was executed in PubMed, Embase, Web of Science, OVID, and the Cochrane Library for relevant studies up to February 2023. The applicable data were extracted from the eligible studies, and the risk of bias was assessed for each study. The meta-analysis was conducted using Review Manager (version 5.4.1) and Stata (version 15.1). RESULTS: A total of 12 studies were included in the final analysis. Compared to the model control group, the MSC therapy group presented lower frequency of sneezing [(Standardized mean difference (SMD) -1.87, 95% CI -2.30 to -1.43)], nasal scratching (SMD -1.41, 95% CI -1.83 to -0.99), and overall nasal symptoms (SMD -1.88, 95% CI -3.22 to -0.54). There were also remarkable reductions after transplantation with MSCs in the levels of total immunoglobulin E (IgE) (SMD -1.25, 95% CI -1.72 to -0.79), allergen-specific IgE (SMD -1.79, 95% CI -2.25 to -1.32), and allergen-specific immunoglobulin G1 (SMD -1.29, 95% CI -2.03) in serum, as well as the count of eosinophils (EOS) in nasal mucosa (SMD -3.48, 95% CI -4.48 to -2.49). In terms of cytokines, MSC therapy significantly decreased both protein and mRNA levels of T helper cell 2 (Th2)-related cytokines, including interleukin (IL)-4, IL-5, IL-10, and IL-13. CONCLUSION: MSC therapy has the potential to be an effective clinical treatment for AR patients by attenuating Th2 immune responses, reducing secretion of IgE and nasal infiltration of EOS, and consequently alleviating nasal symptoms.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Rinite Alérgica , Animais , Humanos , Rinite Alérgica/tratamento farmacológico , Mucosa Nasal , Citocinas/metabolismo , Modelos Animais de Doenças , Imunoglobulina E/metabolismo , Alérgenos/farmacologia , Células-Tronco Mesenquimais/metabolismo
18.
Nat Commun ; 14(1): 6779, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880227

RESUMO

Intestinal organoid transplantation is a promising therapy for the treatment of mucosal injury. However, how the transplanted organoids regulate the immune microenvironment of recipient mice and their role in treating intestinal ischemia-reperfusion (I/R) injury remains unclear. Here, we establish a method for transplanting intestinal organoids into intestinal I/R mice. We find that transplantation improve mouse survival, promote self-renewal of intestinal stem cells and regulate the immune microenvironment after intestinal I/R, depending on the enhanced ability of macrophages polarized to an anti-inflammatory M2 phenotype. Specifically, we report that L-Malic acid (MA) is highly expressed and enriched in the organoids-derived conditioned medium and cecal contents of transplanted mice, demonstrating that organoids secrete MA during engraftment. Both in vivo and in vitro experiments demonstrate that MA induces M2 macrophage polarization and restores interleukin-10 levels in a SOCS2-dependent manner. This study provides a therapeutic strategy for intestinal I/R injury.


Assuntos
Macrófagos , Traumatismo por Reperfusão , Camundongos , Animais , Organoides/transplante , Isquemia/terapia
19.
J Environ Manage ; 347: 119076, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37748299

RESUMO

Excessive phosphorus (P) in surface water can lead to serious eutrophication and economic losses. Iron-based constructed wetland (CW) is considered as a promising solution to eliminate P effectively due to the advantage of low-cost. However, there is limited available information on the microbial removal mechanism of P in iron-based CW up to now. Therefore, CW with iron scrap was constructed to investigate the treatment performance and microbial removal mechanism in this study. Results showed that efficient and stable P removal (97.09 ± 1.90%) was achieved in iron scrap-based CW during the experiment period, which was attributed to the precipitation of iron and P and improved microbially mediated P removal. Metagenomic analysis showed that microbial diversity was enhanced and phosphate accumulating organisms (e.g., Dechloromonas and Tetrasphaera) were enriched in CW with iron scrap, which explained higher P removal reasonably. In addition, the abundance of genes involved in the P starvation (e.g., phoB), uptake and transport (e.g., pstB) were enhanced in iron scrap-based CW. Enrichment analysis demonstrated that phosphotransferase pathway was also significantly up-regulated in CW with iron scraps, indicating that the energy supply of microbial P removal was enhanced. These findings provide a better understanding of the microbial removal mechanism of P in iron-based CW.


Assuntos
Fontes de Energia Bioelétrica , Águas Residuárias , Áreas Alagadas , Ferro , Fósforo
20.
J Hazard Mater ; 459: 132235, 2023 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-37562349

RESUMO

Struvite recovered from wastewater contains high concentration of fecal indicator bacteria (FIB), porcine adenoviruses (PAdV) and antibiotic resistance genes (ARGs), becoming potential resources of these microbial hazards. Understanding the precipitation behavior of pathogenic indicators and ARGs with suspended solids (SS) will provide the possible strategy for the control of co-precipitation. In this study, SS was divided into high-density SS (separated by centrifugation) and low-density SS (further separated by filtration), and the role of SS on the co-precipitation of FIB, PAdV and ARGs was investigated. The distribution analysis showed that 35.5-73.0% FIB, 79.6% PAdV and 64.5-94.8% ARGs existed in high-density SS, while the corresponding values were 26.9-64.4%, 11.7% and 3.5-24.3% in low-density SS. During struvite generation, 82.7-96.9% FIB, 75.5% PAdV and 56.3-86.5% ARGs were co-precipitated into struvite. High-density SS contributed 20.7-68.5% FIB, 63.9% PAdV and 38.7-87.2% ARGs co-precipitation, and the corresponding contribution of low-density SS was 31.4-79.2%, 3.9% and 6.2-54.7%. Moreover, the precipitated SS in struvite obviously decreased inactivation efficiency of FIB and ARGs in drying process. These results provide a potential way to control the co-precipitation and inactivation of FIB, PAdV and ARGs in struvite through removing high-density SS prior to struvite recovery.


Assuntos
Fosfatos , Águas Residuárias , Suínos , Animais , Estruvita , Fosfatos/análise , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos , Genes Bacterianos
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