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1.
J Exp Bot ; 75(1): 103-122, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37725963

RESUMO

Plants are commonly exposed to abiotic stressors, which can affect their growth, productivity, and quality. Previously, the maize transcription factor ZmCCT was shown to be involved in the photoperiod response, delayed flowering, and quantitative resistance to Gibberella stalk rot. In this study, we demonstrate that ZmCCT can regulate plant responses to drought. ZmCCT physically interacted with ZmFra a 1, ZmWIPF2, and ZmAux/IAA8, which localized to the cell membrane, cytoplasm, and nucleus, respectively, both in vitro and in vivo in a yeast two-hybrid screen in response to abiotic stress. Notably, ZmCCT recruits ZmWIPF2 to the nucleus, which has strong E3 self-ubiquitination activity dependent on its RING-H2 finger domain in vitro. When treated with higher indole-3-acetic acid/abscisic acid ratios, the height and root length of Y331-ΔTE maize plants increased. Y331-ΔTE plants exhibited increased responses to exogenously applied auxin or ABA compared to Y331 plants, indicating that ZmCCT may be a negative regulator of ABA signalling in maize. In vivo, ZmCCT promoted indole-3-acetic acid biosynthesis in ZmCCT-overexpressing Arabidopsis. RNA-sequencing and DNA affinity purification-sequencing analyses showed that ZmCCT can regulate the expression of ZmRD17, ZmAFP3, ZmPP2C, and ZmARR16 under drought. Our findings provide a detailed overview of the molecular mechanism controlling ZmCCT functions and highlight that ZmCCT has multiple roles in promoting abiotic stress tolerance.


Assuntos
Arabidopsis , Ubiquitina-Proteína Ligases , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Zea mays/genética , Zea mays/metabolismo , Resistência à Seca , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/genética , Ácido Abscísico/metabolismo , Ácidos Indolacéticos/metabolismo , Arabidopsis/genética , Secas , Estresse Fisiológico/genética
2.
Environ Sci Technol ; 58(5): 2247-2259, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38179619

RESUMO

Both the gut microbiome and their host participate in arsenic (As) biotransformation, while their exact roles and mechanisms in vivo remain unclear and unquantified. In this study, as3mt-/- zebrafish were treated with tetracycline (TET, 100 mg/L) and arsenite (iAsIII) exposure for 30 days and treated with probiotic Lactobacillus rhamnosus GG (LGG, 1 × 108 cfu/g) and iAsIII exposure for 15 days, respectively. Structural equation modeling analysis revealed that the contribution rates of the intestinal microbiome to the total arsenic (tAs) and inorganic As (iAs) metabolism approached 44.0 and 18.4%, respectively. Compared with wild-type, in as3mt-/- zebrafish, microbial richness and structure were more significantly correlated with tAs and iAs, and more differential microbes and microbial metabolic pathways significantly correlated with arsenic metabolites (P < 0.05). LGG supplement influenced the microbial communities, significantly up-regulated the expressions of genes related to As biotransformation (gss and gst) in the liver, down-regulated the expressions of oxidative stress genes (sod1, sod2, and cat) in the intestine, and increased arsenobetaine concentration (P < 0.05). Therefore, gut microbiome promotes As transformation and relieves As accumulation, playing more active roles under iAs stress when the host lacks key arsenic detoxification enzymes. LGG can promote As biotransformation and relieve oxidative stress under As exposure.


Assuntos
Arsênio , Microbioma Gastrointestinal , Animais , Peixe-Zebra , Fígado/metabolismo , Biotransformação , Metiltransferases/genética , Metiltransferases/metabolismo
3.
Ecotoxicol Environ Saf ; 274: 116147, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38460405

RESUMO

Arsenic, a ubiquitous environmental toxicant with various forms and complex food matrix interactions, can reportedly exert differential effects on the liver compared to drinking water exposure. To examine its specific liver-related harms, we targeted the liver in C57BL/6 J mice (n=48, 8-week-old) fed with arsenic-contaminated food (30 mg/kg) for 60 days, mimicking the rice arsenic composition observed in real-world scenarios (iAsV: 7.3%, iAsIII: 72.7%, MMA: 1.0%, DMA: 19.0%). We then comprehensively evaluated liver histopathology, metabolic changes, and the potential role of the gut-liver axis using human hepatocellular carcinoma cells (HepG2) and microbiota/metabolite analyses. Rice arsenic exposure significantly altered hepatic lipid (fatty acids, glycerol lipids, phospholipids, sphingolipids) and metabolite (glutathione, thioneine, spermidine, inosine, indole-derivatives, etc.) profiles, disrupting 33 metabolic pathways (bile secretion, unsaturated fatty acid biosynthesis, glutathione metabolism, ferroptosis, etc.). Pathological examination revealed liver cell necrosis/apoptosis, further confirmed by ferroptosis induction in HepG2 cells. Gut microbiome analysis showed enrichment of pathogenic bacteria linked to liver diseases and depletion of beneficial strains. Fecal primary and secondary bile acids, short-chain fatty acids, and branched-chain amino acids were also elevated. Importantly, mediation analysis revealed significant correlations between gut microbiota, fecal metabolites, and liver metabolic alterations, suggesting fecal metabolites may mediate the impact of gut microbiota and liver metabolic disorders. Gut microbiota and its metabolites may play significant roles in arsenic-induced gut-liver injuries. Overall, our findings demonstrate that rice arsenic exposure triggers oxidative stress, disrupts liver metabolism, and induces ferroptosis.


Assuntos
Arsênio , Microbiota , Camundongos , Humanos , Animais , Arsênio/toxicidade , Camundongos Endogâmicos C57BL , Fígado , Glutationa , Metabolismo dos Lipídeos
4.
J Liposome Res ; : 1-13, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563474

RESUMO

ABSTACTThe medicinal properties of genetic drugs are highly dependent on the design of delivery systems. Ionizable cationic lipids are considered core materials in delivery systems. However, there has not yet been a widespread consensus on the relationship between the wide diversity of lipid structure design and gene delivery efficiency. The aims of the research work were to synthesize ionizable cholesterol derivatives (iChol-lipids) and to evaluate their potential applications as gene delivery vector. A series of iChol-lipids with different head groups were synthesized with carbamate bond spacer. The chemical structures were characterized by 1H NMR, MS, melting range, and pKa. The interactions between iChol-lipids and MALAT1-siRNA were studied by molecular dynamics simulations and compared with market available DC-Chol, which revealed that hydrogen bonds, salt-bridge, and electrostatic interaction were probably involved. The self-assemble behaviors of these lipids were intensively investigated and evaluated by dynamic laser scattering in the presence of different helper lipids and PEGylated lipids. Their plasmid binding ability, transfection efficiency, hemolytic toxicity, and cytotoxicity were fully studied. IZ-Chol-LNPs was proved to be highly potential to effectively complex with DNA, and endosome escape mechanisms mediated by proton sponge effect was verified by pH-sensitive fluorescence probe BCFL.

5.
Reprod Biol Endocrinol ; 21(1): 121, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110998

RESUMO

BACKGROUND: To explore the role of anti-Mullerian hormone (AMH) in predicting the need to step up recombinant FSH (rFSH) dose following long GnRH agonist protocol in IVF/ICSI cycles of polycystic ovarian syndrome (PCOS) women. METHODS: This is a retrospective cohort study of 825 PCOS women undergoing long GnRH agonist protocol enrolled from Jan 2019 to Dec 2021. The daily rFSH dose at which the first response to rFSH were recorded. The dose at which the first response to rFSH was based on folliculometry during follow up in which two or more follicles reached ≥ 11 mm. A receiver operating characteristic (ROC) curve analysis was done to investigate the ability of AMH to predict the need to step up initial rFSH dose. RESULTS: PCOS women who needed to step up initial rFSH dose had a significantly higher AMH compared with those didn't step up initial rFSH dose (11.37 ± 3.25ng/ml vs. 8.69 ± 3.16ng/ml, p < 0.001). In multivariate logistic regression analysis, increased AMH level was an independent factor for the need to step up initial rFSH dose in PCOS patients after adjusted for confounding factors. ROC curve analysis showed AMH could predict the need to step up initial rFSH dose (AUC = 0.738, 95%CI: 0.704-0.773), having 75.4% specificity and 63% sensitivity when the threshold AMH concentration was 9.30ng/ml. 58.8% PCOS women with AMH > 9.30 ng/ml required increased rFSH dose compared to 18.8% of women with AMH ≤ 9.30ng/ml (p < 0.001). Although the clinical pregnancy rate and live birth rate were not significantly different, there was a higher incidence of OHSS among women with AMH > 9.30 ng/ml vs. AMH ≤ 9.30ng/ml (20.8% vs. 15.3%, p = 0.043). CONCLUSION: PCOS women with AMH > 9.30 ng/ml were resistant to rFSH stimulation and require increased dose for the cycle recruitment of ovarian follicles.


Assuntos
Hormônio Antimülleriano , Hormônio Foliculoestimulante Humano , Hormônio Liberador de Gonadotropina , Síndrome do Ovário Policístico , Feminino , Humanos , Gravidez , Hormônio Antimülleriano/sangue , Fertilização in vitro/métodos , Hormônio Foliculoestimulante Humano/uso terapêutico , Hormônio Liberador de Gonadotropina/agonistas , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/tratamento farmacológico , Estudos Retrospectivos
6.
Crit Rev Food Sci Nutr ; : 1-14, 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36876514

RESUMO

Lipopeptides, a class of compounds consisting of a peptide ring and a fatty acid chain, are secondary metabolites produced by Bacillus spp. As their hydrophilic and oleophilic properties, lipopeptides are widely used in food, medicine, environment and other industrial or agricultural fields. Compared with artificial synthetic surfactants, microbial lipopeptides have the advantages of low toxicity, high efficiency and versatility, resulting in urgent market demand and broad development prospect of lipopeptides. However, due to the complex metabolic network and precursor requirements of synthesis, the specific and strict synthesis pathway, and the coexistence of multiple homologous substances, the production of lipopeptides by microorganisms has the problems of high cost and low production efficiency, limiting the mass production of lipopeptides and large-scale application in industry. This review summarizes the types of Bacillus-produced lipopeptides and their biosynthetic pathways, introduces the versatility of lipopeptides, and describes the methods to improve the production of lipopeptides, including genetic engineering and optimization of fermentation conditions.

7.
Inflamm Res ; 72(3): 603-621, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36690783

RESUMO

OBJECTIVE: To explore the molecular mechanism of γ-glutamylcysteine (γ-GC) in response to inflammation in vivo and in vitro on regulating the polarization of macrophages. METHODS: The expressions of gene or protein were assessed by qPCR and Western blot assays, respectively. Cell viability was investigated by CCK-8 assay. Eight-week-old male BALB/c mice were established to examine the therapeutic effects of γ-GC in vivo. The release of TNF-α and IL-4 was determined by ELISA assay. Macrophages polarization was identified by flow cytometry assay. RESULTS: Our data showed that γ-GC treatment significantly improved the survival, weight loss, and colon tissue damage of IBD mice. Furthermore, we established M1- and M2-polarized macrophages, respectively, and our findings provided evidence that γ-GC switched M1/M2-polarized macrophages through activating AMPK/SIRT1 axis and inhibiting inflammation-related signaling pathway. CONCLUSION: Collectively, both in vivo and in vitro experiments suggested that γ-GC has the potential to become a promising novel therapeutic dipeptide for the treatment of IBD, which provide new ideas for the treatment of inflammatory diseases in the future.


Assuntos
Doenças Inflamatórias Intestinais , Masculino , Animais , Camundongos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Macrófagos/metabolismo , Inflamação/metabolismo , Dipeptídeos/farmacologia , Dipeptídeos/uso terapêutico , Dipeptídeos/metabolismo
8.
Intervirology ; 66(1): 111-121, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37793363

RESUMO

INTRODUCTION: Human enterovirus D68 (EV-D68), which belongs to enteroviruses of the small RNA family, is a type of enterovirus that can cause acute respiratory tract infection and central nervous system diseases. This study systematically analysed and summarized EV-D68 antibody studies in databases and identified the seropositivity rates of different regions, ages, and sexes. METHODS: Meta-analysis was performed using STATA 16.0 software. I2 and Q tests were used to analyse the heterogeneity of the included studies. Meta-regression analysis was performed for different groups, and Egger's linear regression analysis was used to evaluate publication bias. RESULTS: The results of multiple studies indicated that the serological prevalence range of EV-D68 antibody was 17.78-96.69%. The results of the meta-analysis showed that the seropositivity rate of EV-D68 antibody was 76% (95% confidence interval [CI]: 67-84%), among which that of the Chinese population was 74% (95% CI: 61-86%) and that of other countries was 79% (95% CI: 65-91%). At the same time, a subgroup analysis was conducted. The seroprevalence of EV-D68 antibody was related to age but not sex or region. CONCLUSION: The seropositivity rate was lower in the below 5-year age group; however, it gradually increased with age. The results of this study showed that EV-D68 infection was widespread in the population, and the current clinical infection situation could not reflect the actual epidemic situation of the virus, among which children under 5 years old were vulnerable to infection, which should be given greater attention for epidemic prevention and control.


Assuntos
Enterovirus Humano D , Infecções por Enterovirus , Enterovirus , Infecções Respiratórias , Criança , Humanos , Pré-Escolar , Enterovirus Humano D/genética , Estudos Soroepidemiológicos , Infecções por Enterovirus/epidemiologia , Anticorpos Antivirais , Infecções Respiratórias/epidemiologia
9.
Arch Virol ; 168(2): 37, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609748

RESUMO

Hand, foot, and mouth disease (HFMD) is a common infectious disease in children. Enterovirus A71 (EV-A71) is one of the main pathogens, and coxsackievirus A6 (CVA6) has gradually become the dominant pathogen of HFMD in recent years. This study was conducted mainly to assess the serological prevalence of EV-A71 and CVA6 antibodies in people of different ages, sexes, and regions through a systematic review and meta-analysis. A comprehensive study was performed based on the EV-A71 and CVA6 serological literature published before May 2022. Heterogeneity analysis (Cochrane's Q test and the I2 statistic) and random effect models were adopted. Subgroup and meta-regression analyses were used to identify potential sources of heterogeneity in the data, and all analysis was performed using STATA version 16.0. This study included 71 studies involving 55,176 people from 13 countries that met the inclusion criteria. The serological prevalence of EV-A71 antibody in different studies was 4.31-88.8%, and that of CVA6 antibody was 40.8-80.9%. Meta-analysis results showed that the serum positive rate for EV-A71 antibody was 45.9% (95% CI: 37.6-54.1%). The rate in the Chinese population was 47.8% (95% CI: 42.4-53.2%), and in the other countries, it was 38% (95% CI: 23-55%). The serum positive rate for CVA6 antibody was 58.3% (95% CI: 46.5-70.2%). The rate in the Chinese population was 49.1% (95% CI: 38.3-59.9%), and in the other countries, it was 68% (95% CI: 51-83%). Subgroup analysis was also conducted. The seroprevalence of EV-A71 and CVA6 antibodies is related to age rather than gender or region. The rates of EV-A71 and CVA6 seropositivity are considerably lower in children younger than five years of age. However, the rates gradually increase with age. The findings of this study suggest that children under five years of age may be susceptible to EV-A71 and CVA6. Thus, safety education and vaccination should be strengthened accordingly. This study provides a basis for understanding the risk factors for EV-A71 and CVA6 infection in China and for deciding how to formulate standard preventive measures to prevent the spread of the virus.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Doença de Mão, Pé e Boca , Criança , Humanos , Pré-Escolar , Doença de Mão, Pé e Boca/epidemiologia , Estudos Soroepidemiológicos , Infecções por Enterovirus/epidemiologia , Anticorpos Antivirais , China/epidemiologia
10.
Environ Res ; 231(Pt 3): 116255, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37245578

RESUMO

The formation of black and odorous water is a complex process influenced by various factors such as organic matter and environmental conditions. However, there are limited studies on the role of microorganisms in water and sediment during the blackening and odorization process. In this study, we investigated the characteristics of black and odorous water formation by simulating organic carbon-driven black and odorous water through indoor experiments. The study revealed that the water turned black and odorous when DOC reached 50 mg/L and the microbial community structure in the water changed significantly during this process, with the relative abundance of Desulfobacterota increasing significantly and Desulfovibrio being the main dominant genus in Desulfobacterota. Additionally, we observed a notable decrease in the α-diversity of the microbial community in water and a considerable increase in microbial function of sulfur compounds respiration in water. In contrast, the sediment microbial community changed slightly, and the main functions of the sediment microbial community remained unchanged. The partial least squares path model (PLS-PM) suggested that organic carbon will drive the blackening and odorization process by affecting DO levels and microbial community structure and that the contribution of Desulfobacterota in water to the formation of black and odorous water was higher than that in sediment. Overall, our study provides insights into the characteristics of black and odorous water formation and suggests potential ways to prevent its formation by controlling DOC and inhibiting the growth of Desulfobacterota in water bodies.


Assuntos
Carbono , Água , Compostos de Enxofre , Odorantes
11.
Phytother Res ; 37(2): 367-382, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36331009

RESUMO

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by flora disequilibrium and mucosal immunity disorder. Here, we report that salidroside effectively restricts experimental colitis from two aspects of intestinal macrophage pyroptosis and dysbacteriosis-derived colonic Th17/Treg imbalance. In innate immunity, the upregulated TREM1 and pyroptosis-related proteins in inflamed colons were inhibited by salidroside administration and further experiments in vitro showed that salidroside suppressed LPS/ATP-induced bone marrow-derived macrophages (BMDMs) pyroptosis evident by the decline of LDH and IL-1ß release as well as the protein level of NLRP3, caspase-1, and GSDMD p30. Moreover, the TREM1 inhibitor weakened the effect of salidroside on BMDMs pyroptosis, whereas salidroside still could downregulate TREM1 when NLRP3 was inhibited. In adaptive immunity, salidroside improved the gut microflora diversity and Th17/Treg ratio in DSS-induced mice, especially promoting the abundance of Firmicutes. Clearance of the gut flora blocked the benefit of salidroside on colonic inflammation and Th17/Treg adaptive immunity, but transplanting salidroside-treated foecal bacterium into flora-depleted wild mice reproduced the resistance of salidroside to gut inflammation. Taken together, our data demonstrated that salidroside protected experimental colitis via skewing macrophage pyroptosis and Th17/Treg balance, indicating its potential effect on UC and other immune disorders.


Assuntos
Colite Ulcerativa , Colite , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Piroptose , Linfócitos T Reguladores/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Disbiose , Colite/induzido quimicamente , Macrófagos/metabolismo , Inflamação/metabolismo , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL
12.
Sensors (Basel) ; 23(11)2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37300063

RESUMO

Compared to fixed orthodontic appliances with brackets, thermoplastic invisible orthodontic aligners offer several advantages, such as high aesthetic performance, good comfort, and convenient oral health maintenance, and are widely used in orthodontic fields. However, prolonged use of thermoplastic invisible aligners may lead to demineralization and even caries in most patients' teeth, as they enclose the tooth surface for an extended period. To address this issue, we have created PETG composites that contain piezoelectric barium titanate nanoparticles (BaTiO3NPs) to obtain antibacterial properties. First, we prepared piezoelectric composites by incorporating varying amounts of BaTiO3NPs into PETG matrix material. The composites were then characterized using techniques such as SEM, XRD, and Raman spectroscopy, which confirmed the successful synthesis of the composites. We cultivated biofilms of Streptococcus mutans (S. mutans) on the surface of the nanocomposites under both polarized and unpolarized conditions. We then activated piezoelectric charges by subjecting the nanocomposites to 10 Hz cyclic mechanical vibration. The interactions between the biofilms and materials were evaluated by measuring the biofilm biomass. The addition of piezoelectric nanoparticles had a noticeable antibacterial effect on both the unpolarized and polarized conditions. Under polarized conditions, nanocomposites demonstrated a greater antibacterial effect than under unpolarized conditions. Additionally, as the concentration of BaTiO3NPs increased, the antibacterial rate also increased, with the surface antibacterial rate reaching 67.39% (30 wt% BaTiO3NPs). These findings have the potential for application in wearable, invisible appliances to improve clinical services and reduce the need for cleaning methods.


Assuntos
Nanocompostos , Streptococcus mutans , Humanos , Biofilmes , Antibacterianos/farmacologia , Antibacterianos/química , Nanocompostos/química
13.
Water Sci Technol ; 87(11): 2776-2792, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37318923

RESUMO

Black-odorous water is a severe environmental issue that has received continuous attention. The major purpose of the present study was to propose an economical, practical, and pollution-free treatment technology. In this study, the in situ remediation of black-odorous water was conducted by applying different voltages (2.5, 5, and 10 V) to improve oxidation conditions of the surface sediments. The study investigated the effects of voltage intervention on water quality, gas emissions, and microbial community dynamics in surface sediments during the remediation process. The results indicated that the voltage intervention can effectively increase the oxidation-reduction potential (ORP) of the surface sediments and inhibit the emissions of H2S, NH3, and CH4. Moreover, the relative abundances of typical methanogens (Methanosarcina and Methanolobus) and sulfate-reducing bacteria (Desulfovirga) decreased because of the increase in ORP after the voltage treatment. The microbial functions predicted by FAPROTAX also demonstrated the inhibition of methanogenesis and sulfate reduction functions. On the contrary, the total relative abundances of chemoheterotrophic microorganisms (e.g., Dechloromonas, Azospira, Azospirillum, and Pannonibacter) in the surface sediments increased significantly, which led to enhanced biochemical degradability of the black-odorous sediments as well as CO2 emissions.


Assuntos
Sedimentos Geológicos , Microbiota , Sedimentos Geológicos/química , Oxirredução , Sulfatos
14.
Geriatr Nurs ; 54: 192-198, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37801874

RESUMO

This study aims to investigate the status and influencing factors of two-way social support among old adults. A cross-sectional study of 408 convenient samples of old adults was conducted using socio-demographic questionnaire, Brief 2-Way Social Support Scale, Modified Barthel index, General Well-being Schedule, Family APGAR Index, and Lubben Social Network Scale 6. The two-way social support score for old adults in China was (43.74±7.86), with the receiving and giving social support scoring (22.80±4.06) and (20.94±4.52), respectively. The multiple linear regression analysis revealed that family care, residence place, socioeconomic status, and social network were associated with both receiving and giving social support. Chronic diseases and religious beliefs were related to receiving social support, while gender, general well-being, and residence form were related to giving social support. Tailored interventions based on the distinct influencing factors are needed to enhance old adults' social support both as recipients and providers.


Assuntos
Apoio Social , Humanos , Estudos Transversais , Fatores Socioeconômicos , China , Inquéritos e Questionários
15.
J Nanobiotechnology ; 20(1): 261, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35672752

RESUMO

Adoptive cell therapy (ACT) was one of the most promising anti-tumor modalities that has been confirmed to be especially effective in treating hematological malignancies. However, the clinical efficacy of ACT on solid tumor was greatly hindered by the insufficient tumor-infiltration of cytotoxic CD8 + T cells. Herein, we constructed a nanoplatform termed dual-binding magnetic nanoparticles (DBMN) that comprised PEG-maleimide (Mal), hyaluronic acid (HA) and Fe3O4 for adoptive T cell-modification and ACT-sensitization. After a simple co-incubation, DBMN was anchored onto the cell membrane (Primary linking) via Michael addition reaction between the Mal and the sulfhydryl groups on the surface of T cells, generating magnetized T cells (DBMN-T). Directed by external magnetic field and in-structure Fe3O4, DBMN-T was recruited to solid tumor where HA bond with the highly expressed CD44 on tumor cells (Secondary Linking), facilitating the recognition and effector-killing of tumor cells. Bridging adoptive T cells with host tumor cells, our DBMN effectively boosted the anti-solid tumor efficacy of ACT in a mouse model and simultaneously reduced toxic side effects.


Assuntos
Nanopartículas , Neoplasias , Animais , Linhagem Celular Tumoral , Ácido Hialurônico/química , Campos Magnéticos , Camundongos , Nanopartículas/química , Neoplasias/patologia , Neoplasias/terapia , Linfócitos T Citotóxicos
16.
Cell Mol Life Sci ; 79(1): 54, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34936032

RESUMO

Glutathione S-transferase pi (GSTpi) is an important phase II detoxifying enzyme that participates in various physiological processes, such as antioxidant, detoxification, and signal transduction. The high expression level of GSTpi has been reported to be related to drug-resistant and anti-inflammatory and it functioned via its non-catalytic ligandin. However, the previous protection mechanism of GSTpi in DNA damage has not been addressed so far. Nijmegen breakage syndrome 1 (NBS1) is one of the most important sensor proteins to detect damaged DNA. Here, we investigated the interaction between GSTpi and NBS1 in HEK-293 T cells and human breast adenocarcinoma cells during DNA damage. Our results showed that overexpression of GSTpi in cells by transfecting DNA vector decreased the DNA damage level after methyl methanesulfonate (MMS) or adriamycin (ADR) treatment. We found that cytosolic GSTpi could increase NBS1 ubiquitin-mediated degradation in unstimulated cells, which suggested that GSTpi could maintain the basal level of NBS1 during normal conditions. In response to DNA damage, GSTpi can be phosphorylated in Ser184 and inhibit the ubiquitination degradation of NBS1 mediated by Skp2 to recover NBS1 protein level. Phosphorylated GSTpi can further enhance NBS1 nuclear translocation to activate the ATM-Chk2-p53 signaling pathway. Finally, GSTpi blocked the cell cycle in the G2/M phase to allow more time for DNA damage repair. Thus, our finding revealed the novel mechanism of GSTpi via its Ser184 phosphorylation to protect cells from cell death during DNA damage and it enriches the function of GSTpi in drug resistance.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Dano ao DNA , Glutationa S-Transferase pi/fisiologia , Síndrome de Quebra de Nijmegen/metabolismo , Proteínas Nucleares/metabolismo , Células HEK293 , Humanos , Células MCF-7 , Fosforilação , Ubiquitinação
17.
Retina ; 42(3): 417-425, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34861657

RESUMO

PURPOSE: Widefield swept-source optical coherence tomography (OCT) imaging was used to characterize choroidal thickness and vascularity at baseline in proliferative diabetic retinopathy (PDR) and longitudinally after panretinal photocoagulation (PRP). METHODS: Patients with treatment-naive PDR were imaged at baseline and at 1 week, 1 month, and 3 months after PRP. Previously validated algorithms were used to calculate the mean choroidal thickness (MCT) and choroidal vascularity index (CVI) in 5 regions of 12 mm × 12 mm scans. RESULTS: Fourteen PDR eyes were included. Baseline MCT in PDR eyes did not differ significantly from normal eyes, but CVI measurements in PDR eyes were lower in all regions (P < 0.001-0.008). After PRP, MCT measurements in PDR eyes were significantly lower at 1 month and 3 months in all regions (P < 0.001-0.005) except the fovea (P = 0.074). However, CVI measurements did not change over time in any region after PRP. CONCLUSION: The choroid in PDR eyes has a smaller CVI than that in normal eyes. After PRP, the choroidal thickness decreases outside the fovea, but the CVI remains constant, which suggests that a relative decrease in choroidal vascularity persists. These widefield swept-source OCT results are consistent with choroidal alterations found in histopathological reports of diabetic choroidopathy.


Assuntos
Doenças da Coroide/diagnóstico por imagem , Corioide/diagnóstico por imagem , Retinopatia Diabética/diagnóstico por imagem , Fotocoagulação a Laser/métodos , Tomografia de Coerência Óptica , Adulto , Idoso , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Corioide/irrigação sanguínea , Doenças da Coroide/fisiopatologia , Doenças da Coroide/cirurgia , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/cirurgia , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia
18.
Retina ; 42(11): 2031-2038, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36067421

RESUMO

PURPOSE: Choriocapillaris (CC) flow deficits (FDs) were measured in the areas exposed by tears of the retinal pigment epithelium (RPE) before and after their onset to determine their change over time. METHODS: Patients enrolled in a prospective, swept-source optical coherence tomography angiography (SS-OCTA) study were retrospectively reviewed for RPE tears, and scans were evaluated before and after RPE tear formation. Choriocapillaris flow deficits were measured within the bed of the tear and within a symmetric control region. RESULTS: Three patients with RPE tears were imaged before tear formation and for at least 16 months afterward. When the baseline and first posttear visit were compared, CC FDs decreased by 1.0% in the tear region and 1.7% in the control region ( P = 0.84). When the 16-month follow-up visits were compared with the first post-RPE tear visits, CC FDs decreased by 1.9% in tear regions and increased by 1.3% in control regions ( P = 0.37). CONCLUSION: No significant changes in CC FDs were observed before and after RPE tear formation and for 16 months afterward, suggesting that CC FDs can be reliably detected in the presence of an intact RPE and the absence of the RPE did not affect CC perfusion for at least 16 months.


Assuntos
Epitélio Pigmentado da Retina , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Angiofluoresceinografia/métodos , Estudos Prospectivos , Estudos Retrospectivos , Corioide
19.
Retina ; 42(9): 1645-1654, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35483032

RESUMO

PURPOSE: Swept-source optical coherence tomography angiography (SS-OCTA) was used to analyze Bruch membrane (BM) and choriocapillaris (CC) abnormalities in undiagnosed family members with Sorsby macular dystrophy (SMD). METHODS: In a family with SMD ( TIMP3 Tyr191Cys), SS-OCTA imaging was performed using the 6 × 6 mm scan patter and previously validated algorithms to detect abnormalities in BM and the CC, as well as the presence of reticular pseudodrusen and macular neovascularization. Genetic analyses were performed for TIMP3 mutations. RESULTS: Of eight family members, two were previously diagnosed with SMD and six were asymptomatic. SS-OCTA imaging of the 33-year-old proband revealed type 1 macular neovascularization in the left eye and bilateral reticular pseudodrusen, thickening of BM, CC thinning, and increases in CC flow deficits. A TIMP3 mutation was confirmed. His niece, despite having no clinical evidence of SMD, showed BM thickening and CC thinning on SS-OCTA. A TIMP3 mutation was confirmed. The proband's younger nephew and niece also carried the TIMP3 mutation without clinical evidence of SMD. Two additional members had normal examinations, unremarkable SS-OCTA findings, and no TIMP3 mutation. CONCLUSION: Swept-source optical coherence tomography angiography imaging can detect BM and CC abnormalities in vivo in subjects unaware of their TIMP3 status in a family with SMD.


Assuntos
Anormalidades do Olho , Degeneração Macular , Drusas Retinianas , Distrofias Retinianas , Adulto , Lâmina Basilar da Corioide , Corioide , Angiofluoresceinografia/métodos , Humanos , Degeneração Macular/diagnóstico , Degeneração Macular/genética , Drusas Retinianas/diagnóstico , Tomografia de Coerência Óptica/métodos
20.
Sensors (Basel) ; 22(20)2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36298303

RESUMO

In recent years, hazardous wastewater treatment has been a complex and global problem. In this work, by considering the antimicrobial activity of Ag nanoparticles (AgNPs) and reduced graphene oxide (rGO), we constructed an antibacterial device (G-AgNP) with AgNPs conformably deposited onto a 3D scaffold of reduced graphene oxide in situ. The major limitation, which is difficult to recycle, of two-dimensional graphene-silver composite materials in previous studies is improved. Characterization techniques, SEM, TEM, XRD, and XPS, confirmed the synthesis of nanocomposites. Attributed to its larger specific area, more active sites, and synergistic enhancement, the G-AgNP device demonstrated the best bacterial removal capacity, with an antibacterial rate for both E. coli and S. aureus as high as 100% at quite low AgNP contents. The reported G-AgNP has potential application as a wearable sewage treatment device and for the protection of wearable sensors as a promising sterilizing candidate based on its high and stable antibacterial efficiency.


Assuntos
Grafite , Nanopartículas Metálicas , Grafite/farmacologia , Grafite/química , Staphylococcus aureus , Escherichia coli , Nanopartículas Metálicas/química , Esgotos , Prata , Antibacterianos/farmacologia , Antibacterianos/química
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