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1.
Chem Eng J ; 4912024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38882000

RESUMO

Immunoassays have been widely used to determine small-molecule compounds in food and the environment, meeting the challenge of obtaining false positive or negative results because of the variance in the batches of antibodies and antigens. To resolve this problem, atrazine (ATR) was used as a target, and anti-idiotypic nanobodies for ATR (AI-Nbs) and a recombinant full-length antibody against ATR (ATR-rAb) were prepared for the development of a sustainable enzyme-linked immunosorbent assay (ELISA). AI-Nb-7, AI-Nb-58, and AI-Nb-66 were selected from an immune phage display library. ATR-rAb was produced in mammalian HEK293 (F) cells. Among the four detection methods explored, the assay using AI-Nb-66 as a coating antigen and ATR-rAb as a detection reagent yielded a half maximal inhibitory concentration (IC50) of 1.66 ng mL-1 for ATR and a linear range of 0.35-8.73 ng mL-1. The cross-reactivity of the assay to ametryn was 64.24%, whereas that to terbutylazine was 38.20%. Surface plasmon resonance (SPR) analysis illustrated that these cross-reactive triazine compounds can bind to ATR-rAb to varying degrees at high concentrations; however, the binding/dissociation kinetic curves and the response values at the same concentration are different, which results in differences in cross-reactivity. Homology modeling and molecular docking revealed that the triazine ring is vital in recognizing triazine compounds. The proposed immunoassay exhibited acceptable recoveries of 84.40-105.36% for detecting fruit, vegetables, and black tea. In conclusion, this study highlights a new strategy for developing sustainable immunoassays for detecting trace pesticide contaminants.

3.
Polymers (Basel) ; 16(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38931998

RESUMO

With the swift progress of the electronics industry, discarded circuit boards have become an important source of non-degradable waste. In this work, discarded epoxy resin was collected as a precursor to prepare activated carbon (AC) through stepwise carbonization/activation methods. The rough carbon materials with a certain graphite and amorphous structure reveal the multiple oxygen-containing groups on their surface. In the process of studying the adsorption of methyl orange by activated carbon, it is found that the adsorption is in accordance with the quasi-secondary kinetic model, and equilibrium adsorption amounts can reach 41.051 mg/g. The adsorption isotherm of AC is more in line with the Langmuir model, and the saturation adsorption amount at three different temperatures is 23.137 mg/g, 30.358 mg/g, and 37.202 mg/g, respectively. The enthalpy (ΔH) is 17.30 KJ/mol in the adsorption process, which indicates that is a physical process with heat-absorbing capabilities. This work is of great significance with regard to the recycling of waste to reduce pollution and in terms of gaining economic benefits.

4.
ACS Appl Mater Interfaces ; 16(22): 29049-29059, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38770760

RESUMO

High-performance photodetectors with the detection capability of linearly polarized light have broad applications in both military and civilian fields. Quasi-one-dimensional ZrS3 as an emerging anisotropic two-dimensional material has come under the spotlight owing to its intriguing properties. However, the performance of the ZrS3 photodetector is seriously restricted by its low responsivity. Herein, a novel high-performance photodetector based on the van der Waals ZrS3/MoS2 heterostructure is proposed. Attributed to the charge trapping-assisted photogating effect, interlayer carrier transitions, and fast spatial separation of the photogenerated electron-hole pairs, the device displays superior photoresponse characteristics ranging from the ultraviolet to the visible spectrum in terms of high responsivity up to 212 A/W, an extraordinary external quantum efficiency of 8.5 × 104%, and a prompt rise/decay time of 0.19/0.38 ms. In addition, owing to the profound birefringence and dichroism effects in ZrS3 together with strong light-matter interactions in the heterostructure, profound linear-polarization sensitivity is demonstrated with a dichroic ratio of about 2.8. Overall, this photodetector not only is integrated with the excellent properties of ZrS3 and monolayer MoS2 but also further enhances the advantages through interlayer couplings, which demonstrate the strong potential of the ZrS3-based devices for high-performance, ultrafast, and polarization-sensitive photodetection.

5.
Immunol Res ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722530

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia, pannus formation, and cartilage and bone destruction. Lysine-specific demethylase 1 (LSD1), an enzyme involved in transcriptional regulation, has an unclear role in synovial inflammation, fibroblast-like synoviocytes migration, and invasion during RA pathogenesis. In this study, we observed increased LSD1 expression in RA synovial tissues and in TNF-α-stimulated MH7A cells. SP2509, an LSD1 antagonist, directly reduced LSD1 expression and reversed the elevated levels of proteins associated with inflammation, apoptosis, proliferation, and autophagy induced by TNF-α. Furthermore, SP2509 inhibited the migratory capacity of MH7A cells, which was enhanced by TNF-α. In CIA models, SP2509 treatment ameliorated RA development, reducing the expression of pro-inflammatory cytokines and alleviating joint pathological symptoms. These findings underscore the significance of LSD1 in RA and propose the therapeutic potential of SP2509.

6.
Biomol Biomed ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38733632

RESUMO

Diabetic nephropathy (DN) is a severe complication of prolonged diabetes, impacting millions worldwide with an increasing incidence. This study investigates the role of tribbles pseudokinase 3 (TRIB3), a protein implicated in the progression of DN, focusing on its mechanisms underlying glomerular damage. Through analysis of the Gene Expression Omnibus (GEO) database, we identified TRIB3 among differentially expressed genes in streptozotocin (STZ)-treated C57BL/6J mice. Both in vitro and in vivo experiments were conducted to examine the effects of TRIB3 inhibition on high glucose (HG)-induced damage in podocytes and DN mouse models. The results demonstrated that TRIB3 inhibition reduced inflammatory responses and extracellular matrix (ECM) production in MPC5 cells, mediated by the downregulation of DNA damage-inducible transcript 3 (DDIT3) - a critical regulator of proinflammatory cytokine secretion and ECM synthesis. Inhibiting TRIB3 decreased inflammatory factors and ECM deposition in diabetic mice in vivo, confirming its pivotal role in DN pathogenesis. These findings indicate that TRIB3 and its interaction with DDIT3 contribute significantly to DN by promoting inflammatory cascades and ECM accumulation, presenting potential therapeutic targets for managing the disease.

7.
ACS Omega ; 9(16): 18032-18045, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38680313

RESUMO

Spherical δ-MnO2 nanoflower materials were synthesized via a facile one-step coprecipitation method through adjusting the molar ratio of KMnO4 to MnSO4. The influence of the molar ratio of the reactants on the crystal structure, morphology, and electrochemical performances was investigated. At a molar ratio of 3.3 for KMnO4 to MnSO4, the spherical δ-MnO2 nanoflowers composed of nanosheets with the highest specific surface area (228.0 m2 g-1) were obtained as electrode materials. In the conventional three-electrode system using 1 M Na2SO4 as an electrolyte, the specific capacitance of the spherical δ-MnO2 nanoflowers reached 172.3 F g-1 at a current density of 1 A g-1. Moreover, even after 5000 cycles at a current density of 5 A g-1, the GCD curves remained essentially unchanged, and the specific capacitance still retained 86.50% of the maximum value. The kinetics of the electrode reaction were preliminarily studied through the linear potential sweep technique to observe diffusion-controlled contribution toward total capacitance. For the spherical δ-MnO2 nanoflower electrode material, diffusion-controlled contribution accounted for 65.1% at low scan rates and still remained significant at high scan rates (100 mV s-1), indicating excellent utilization efficiency of the bulk phase. The as-fabricated asymmetric supercapacitor HFC-7//MnO2-3.3-ASC presented a prominent specific energy of 16.5 Wh kg-1 at the specific power of 450 W kg-1. Even when the specific power reached 9.0 kW kg-1, the energy density still retained 9.5 Wh kg-1.

8.
Food Chem ; 449: 139198, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38574526

RESUMO

The preparation of high specificity and affinity antibodies is challenging due to limited information on characteristic groups of haptens in traditional design strategy. In this study, we first predicted characteristic groups of flurogestone acetate (FGA) using quantitative analysis of molecular surface combined with atomic charge distribution. Subsequently, FGA haptens were rationally designed to expose these identified characteristic groups fully. As a result, seven monoclonal antibodies were obtained with satisfactory performance, exhibiting IC50 values from 0.17 to 0.45 µg/L and negligible cross-reactivities below 1% to other 18 hormones. The antibody recognition mechanism further confirmed hydrogen bonds and hydrophobic interactions involving predicted FGA characteristic groups and specific amino acids in the antibodies contributed to their high specificity and affinity. Finally, one selective and sensitive ic-ELISA was developed for FGA determination with a detection limit as low as 0.12 µg/L, providing an efficient tool for timely monitoring of FGA in goat milk samples.


Assuntos
Anticorpos Monoclonais , Ensaio de Imunoadsorção Enzimática , Contaminação de Alimentos , Cabras , Haptenos , Leite , Animais , Leite/química , Haptenos/química , Haptenos/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Contaminação de Alimentos/análise , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Feminino , Formação de Anticorpos
9.
J Hazard Mater ; 469: 134067, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38513441

RESUMO

High-performance antibodies are core reagents for highly sensitive immunoassays. Herein, based on a novel hapten, a hybridoma secreting the high-affinity anti-ethirimol monoclonal antibody (mAb-14G5F6) was isolated with an IC50 value of 1.35 µg/L and cross-reactivity below 0.20% for 13 analogs. To further address the challenge of hybridoma preservation and antibody immortalization, a recombinant full-length antibody (rAb-14G5F6) was expressed using the HEK293(F) expression system based on the mAb-14G5F6 gene. The affinity, specificity, and tolerance of rAb-14G5F6, as characterized by indirect competitive enzyme-linked immunosorbent assay and noncompetitive surface plasmon resonance, exhibited high concordance with those of mAb-14G5F6. Further immunoassays based on rAb-14G5F6 were developed for irrigation water and strawberry fruit with limits of detection of 0.0066 and 0.036 mg/kg, respectively, recoveries of 80100%, and coefficients of variation below 10%. Furthermore, homology simulation and molecular docking revealed that GLU(L40), GLY(L107), GLY(H108), and ASP(H114) play important roles in forming hydrogen bonds and pi-anion ionic bonds between rAb-14G5F6 and ethirimol, resulting in the high specificity and affinity of rAb-14G5F6 for ethirimol, with a KD of 5.71 × 10-10 mol/L. Overall, a rAb specific for ethirimol was expressed successfully in this study, laying the groundwork for rAb-based immunoassays for monitoring fungicide residues in agricultural products and the environment.


Assuntos
Anticorpos Monoclonais , Frutas , Pirimidinonas , Humanos , Ensaio de Imunoadsorção Enzimática , Frutas/química , Água/análise , Simulação de Acoplamento Molecular , Células HEK293 , Proteínas Recombinantes/genética
10.
Sci Total Environ ; 924: 171703, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38490424

RESUMO

Healthcare-associated infections (HAIs) pose significant risks to pediatric patients in outpatient settings. To prevent HAIs, understanding the sources and transmission routes of pathogenic microorganisms is crucial. This study aimed to identify the sources of opportunistic bacterial pathogens (OBPs) in pediatric outpatient settings and determine their transmission routes. Furthermore, assessing the public health risks associated with the core OBPs is important. We collected 310 samples from various sites in pediatric outpatient areas and quantified the bacteria using qPCR and CFU counting. We also performed 16S rRNA gene and single-bacterial whole-genome sequencing to profile the transmission routes and antibiotic resistance characteristics of OBPs. We observed significant variations in microbial diversity and composition among sampling sites in pediatric outpatient settings, with active communication of the microbiota between linked areas. We found that the primary source of OBPs in multi-person contact areas was the hand surface, particularly in pediatric patients. Five core OBPs, Staphylococcus epidermidis, Acinetobacter baumannii, Pseudomonas aeruginosa, Streptococcus mitis, and Streptococcus oralis, were mainly derived from pediatric patients and spread into the environment. These OBPs accumulated at multi-person contact sites, resulting in high microbial diversity in these areas. Transmission tests confirmed the challenging spread of these pathogens, with S. epidermidis transferring from the patient's hand to the environment, leading to an increased abundance and emergence of related strains. More importantly, S. epidermidis isolated from pediatric patients carried more antibiotic-resistance genes. In addition, two strains of multidrug-resistant A. baumannii were isolated from both a child and a parent, confirming the transmission of the five core OBPs centered around pediatric patients and multi-person contact areas. Our results demonstrate that pediatric patients serve as a significant source of OBPs in pediatric outpatient settings. OBPs carried by pediatric patients pose a high public health risk. To effectively control HAIs, increasing hand hygiene measures in pediatric patients and enhancing the frequency of disinfection in multi-person contact areas remains crucial. By targeting these preventive measures, the spread of OBPs can be reduced, thereby mitigating the risk of HAIs in pediatric outpatient settings.


Assuntos
Antibacterianos , Infecção Hospitalar , Humanos , Criança , RNA Ribossômico 16S , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/prevenção & controle , Staphylococcus epidermidis , Saúde Pública , Testes de Sensibilidade Microbiana
11.
Genes Dis ; 11(4): 101155, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38523676

RESUMO

Genetic mutations in TP53 contribute to human malignancies through various means. To date, there have been a variety of therapeutic strategies targeting p53, including gene therapy to restore normal p53 function, mutant p53 rescue, inhibiting the MDM2-p53 interaction, p53-based vaccines, and a number of other approaches. This review focuses on the functions of TP53 and discusses the aberrant roles of mutant p53 in various types of cancer. Recombinant human p53 adenovirus, trademarked as Gendicine, which is the first anti-tumor gene therapy drug, has made tremendous progress in cancer gene therapy. We herein discuss the biological mechanisms by which Gendicine exerts its effects and describe the clinical responses reported in clinical trials. Notably, the clinical studies suggest that the combination of Gendicine with chemotherapy and/or radiotherapy may produce more pronounced efficacy in slowing tumor growth and progression than gene therapy/chemotherapy alone. Finally, we summarize the methods of administration of recombinant human p53 adenovirus for different cancer types to provide a reference for future clinical trials.

12.
mSystems ; 9(4): e0105523, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38501864

RESUMO

Plant-associated diazotrophs strongly relate to plant nitrogen (N) supply and growth. However, our knowledge of diazotrophic community assembly and microbial N metabolism in plant microbiomes is largely limited. Here we examined the assembly and temporal dynamics of diazotrophic communities across multiple compartments (soils, epiphytic and endophytic niches of root and leaf, and grain) of three cereal crops (maize, wheat, and barley) and identified the potential N-cycling pathways in phylloplane microbiomes. Our results demonstrated that the microbial species pool, influenced by site-specific environmental factors (e.g., edaphic factors), had a stronger effect than host selection (i.e., plant species and developmental stage) in shaping diazotrophic communities across the soil-plant continuum. Crop diazotrophic communities were dominated by a few taxa (~0.7% of diazotrophic phylotypes) which were mainly affiliated with Methylobacterium, Azospirillum, Bradyrhizobium, and Rhizobium. Furthermore, eight dominant taxa belonging to Azospirillum and Methylobacterium were identified as keystone diazotrophic taxa for three crops and were potentially associated with microbial network stability and crop yields. Metagenomic binning recovered 58 metagenome-assembled genomes (MAGs) from the phylloplane, and the majority of them were identified as novel species (37 MAGs) and harbored genes potentially related to multiple N metabolism processes (e.g., nitrate reduction). Notably, for the first time, a high-quality MAG harboring genes involved in the complete denitrification process was recovered in the phylloplane and showed high identity to Pseudomonas mendocina. Overall, these findings significantly expand our understanding of ecological drivers of crop diazotrophs and provide new insights into the potential microbial N metabolism in the phyllosphere.IMPORTANCEPlants harbor diverse nitrogen-fixing microorganisms (i.e., diazotrophic communities) in both belowground and aboveground tissues, which play a vital role in plant nitrogen supply and growth promotion. Understanding the assembly and temporal dynamics of crop diazotrophic communities is a prerequisite for harnessing them to promote plant growth. In this study, we show that the site-specific microbial species pool largely shapes the structure of diazotrophic communities in the leaves and roots of three cereal crops. We further identify keystone diazotrophic taxa in crop microbiomes and characterize potential microbial N metabolism pathways in the phyllosphere, which provides essential information for developing microbiome-based tools in future sustainable agricultural production.


Assuntos
Microbiota , Microbiota/genética , Agricultura , Solo/química , Nitrogênio/análise , Produtos Agrícolas/metabolismo , Desenvolvimento Vegetal
13.
Food Funct ; 15(5): 2706-2718, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38376466

RESUMO

Dietary intake can modify the impact of metals on human health, and is also closely related to glucose metabolism in human bodies. However, research on their interaction is limited. We used data based on 1738 adults aged ≥20 years from the National Health and Nutrition Examination Survey 2011-2016. We combined linear regression and restricted cubic splines with Bayesian kernel machine regression (BKMR) to identify metals associated with each glucose metabolism index (P < 0.05 and the posterior inclusion probabilities of BKMR >0.5) in eight non-essential heavy metals (barium, cadmium, antimony, tungsten, uranium, arsenic, lead, and thallium) and glucose metabolism indexes [fasting plasma glucose (FPG), blood hemoglobin A1c (HbA1c) and homeostatic model assessment of insulin resistance (HOMA-IR)]. We identified two pairs of metals associated with glucose metabolism indexes: cadmium and tungsten to HbA1c and barium and thallium to HOMA-IR. Then, the cross-validated kernel ensemble (CVEK) approach was applied to identify the specific nutrient group (nutrients) that interacted with the association. By using the CVEK model, we identified significant interactions between the energy-adjusted diet inflammatory index (E-DII) and cadmium, tungsten and barium (all P < 0.05); macro-nutrients and cadmium, tungsten and barium (all P < 0.05); minerals and cadmium, tungsten, barium and thallium (all P < 0.05); and A vitamins and thallium (P = 0.043). Furthermore, a lower E-DII, a lower intake of carbohydrates and phosphorus, and a higher consumption of magnesium seem to attenuate the positive association between metals and glucose metabolism indexes. Our finding identifying the nutrients that interact with non-essential heavy metals could provide a feasible nutritional guideline for the general population to protect against the adverse effects of non-essential heavy metals on glucose metabolism.


Assuntos
Cádmio , Metais Pesados , Adulto , Humanos , Inquéritos Nutricionais , Bário , Tálio , Tungstênio , Hemoglobinas Glicadas , Teorema de Bayes , Glucose
14.
Crit Rev Food Sci Nutr ; : 1-12, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38189352

RESUMO

As the world population rises, the demand for protein increases, leading to a widening gap in protein supply. There is an unprecedented interest in the development of alternative proteins, but their allergenicity has raised consumer concerns. This review aims to highlight and correlate the current research status of allergenicity studies on alternative proteins based on previously published studies. Current research keywords, hotspots and trends in alternative protein sensitization were analyzed using a mixed-method approach that combined bibliometric analysis and literature review. According to the bibliometric analysis, current research is primarily focused on food science, agriculture, and immunology. There are significant variations in the type and amount of allergens found in alternative proteins. A significant amount of research has been focused on studying plant-based proteins and the cross-reactivity of insect proteins. The allergenicity of alternative proteins has not been studied extensively or in depth. The allergenicity of other alternative proteins and the underlying mechanisms warrant further study. In addition, the lack of a standardized allergy assessment strategy calls for additional efforts by international organizations and collaborations among different countries. This review provides new research and regulatory perspectives for the safe utilization of alternative proteins in human food systems.

15.
IEEE Trans Image Process ; 33: 709-721, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38190677

RESUMO

Previous methods based on 3DCNN, convLSTM, or optical flow have achieved great success in video salient object detection (VSOD). However, these methods still suffer from high computational costs or poor quality of the generated saliency maps. To address this, we design a space-time memory (STM)-based network that employs a standard encoder-decoder architecture. During the encoding stage, we extract high-level temporal features from the current frame and its adjacent frames, which is more efficient and practical than methods reliant on optical flow. During the decoding stage, we introduce an effective fusion strategy for both spatial and temporal branches. The semantic information of the high-level features is used to improve the object details in the low-level features. Subsequently, spatiotemporal features are methodically derived step by step to reconstruct the saliency maps. Moreover, inspired by the boundary supervision prevalent in image salient object detection (ISOD), we design a motion-aware loss that predicts object boundary motion, and simultaneously perform multitask learning for VSOD and object motion prediction. This can further enhance the model's capability to accurately extract spatiotemporal features while maintaining object integrity. Extensive experiments on several datasets demonstrate the effectiveness of our method and can achieve state-of-the-art metrics on some datasets. Our proposed model does not require optical flow or additional preprocessing, and can reach an impressive inference speed of nearly 100 FPS.

16.
J Agric Food Chem ; 72(4): 2059-2076, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38252458

RESUMO

Fipronil, classified as a phenylpyrazole insecticide, is utilized to control agricultural, public health, and veterinary pests. Notably, its unique ecological fate involves degradation to toxic metabolites, which poses the risk of contamination in water and foodstuffs and potential human exposure through the food chain. In response to these concerns, there is a pressing need to develop analytical methodologies for detecting fipronil and its metabolites. This review provides a concise overview of the mode of action, metabolism, and toxicology of fipronil. Additionally, various detection strategies, encompassing antibody-based immunoassays and emerging analytical techniques, such as fluorescence assays based on aptamer/molecularly imprinted polymer/fluorescent probes, electrochemical sensors, and Raman spectroscopy, are thoroughly reviewed and discussed. The focus extends to detecting fipronil and its metabolites in crops, fruits, vegetables, animal-derived foods, water, and bodily fluids. This comprehensive exploration contributes valuable insights into the field, aiming to foster the development and innovation of more sensitive, rapid, and applicable analytical methods.


Assuntos
Inseticidas , Animais , Humanos , Inseticidas/metabolismo , Pirazóis/química , Imunoensaio , Água
17.
Sci Rep ; 14(1): 2213, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38278873

RESUMO

Field observations in sedimentation and erosion-prone areas indicate that most natural sand deposits may contain a certain amount of non-plastic fines and are often under anisotropic stress conditions. A series of triaxial compression tests were performed on clean and silty sand with fines content fc ranging from 0 to 20% at an initial mean effective stress of p0' = 100 kPa and varying consolidation conditions to understand the impact of initial stress anisotropy on undrained shear behavior. The results indicate that the state parameter ψ is a superior predictor for characterizing the responses of sand-fines mixtures compared to the global void ratio and relative density. A comparison of the behavior of clean and silty sand with a constant ψ (= - 0.03) confirms that the sample with 10% fc exhibits the strongest dilation and greatest shear resistance, irrespective of the consolidation conditions. It is also demonstrated that the initial stress anisotropy with a comparably higher static stress ratio ηs typically diminishes the shear strength of mixtures. However, the influence of initial stress anisotropy on soil stiffness is not unilateral. The sample consolidated to a negative ηs is stiffer than that under isotropic consolidation, while the presence of a positive ηs leads to a decrease in the secant Young's modulus.

18.
Cell Death Dis ; 15(1): 75, 2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38242872

RESUMO

The anti-foreign tissue (transplant rejection) response, mediated by the immune system, has been the biggest obstacle to successful organ transplantation. There are still many enigmas regarding this process and some aspects of the underlying mechanisms driving the immune response against foreign tissues remain poorly understood. Here, we found that a large number of neutrophils and macrophages were attached to the graft during skin transplantation. Furthermore, both types of cells could autonomously adhere to and damage neonatal rat cardiomyocyte mass (NRCM) in vitro. We have demonstrated that Complement C3 and the receptor CR3 participated in neutrophils/macrophages-mediated adhesion and damage this foreign tissue (NRCM or skin grafts). We have provided direct evidence that the damage to these tissues occurs by a process referred to as trogocytosis, a damage mode that has never previously been reported to directly destroy grafts. We further demonstrated that this process can be regulated by NFAT, in particular, NFATc3. This study not only enriches an understanding of host-donor interaction in transplant rejection, but also provides new avenues for exploring the development of novel immunosuppressive drugs which prevent rejection during transplant therapy.


Assuntos
Rejeição de Enxerto , Fatores de Transcrição NFATC , Neutrófilos , Ratos , Animais , Trogocitose , Macrófagos
19.
Aging (Albany NY) ; 16(2): 1712-1732, 2024 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-38244584

RESUMO

OBJECTIVE: Liver cancer is a prevalent disease with a dismal prognosis. The aim of the research is to identify subgroups based on malignant cell receptor ligand gene from single-cell RNA, which might lead to customized immunotherapy for patients with liver cancer. METHODS: Based on scRNA-seq data, we identified the receptor-ligand genes associated with prognosis and classify patients into molecular subtypes by univariate Cox regression and consensus clustering. LASSO regression was performed to construct a prognostic model, which was validated in TCGA and ICGC datasets. Immune infiltration and prediction of immunotherapy response were analyzed using ssGSEA, ESTIMATE, TIDE, and TRS score calculation. Finally, qPCR and Western blot validation of key genes and protein levels in cell lines. RESULTS: A risk model using 16-gene expression levels predicted liver cancer patients' prognosis. The RiskScore associated significantly with tumor clinical characteristics and immunity, integrated with clinicopathological features for survival prediction. Differential expression of SRXN1 was verified in hepatocellular carcinoma and normal liver cells. CONCLUSION: Our study utilizes single-cell analysis to investigate the communication between malignant cells and other cell types, identifying molecular subtypes based on malignant cell receptor ligand genes, offering new insights for the development of personalized immunotherapy and prognostic prediction models.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Ligantes , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Prognóstico , Imunoterapia , Microambiente Tumoral
20.
Neurosci Bull ; 40(2): 255-267, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37391607

RESUMO

Macrophages are essential components of the innate immune system and constitute a non-specific first line of host defense against pathogens and inflammation. Mitochondria regulate macrophage activation and innate immune responses in various inflammatory diseases, including cochlear inflammation. The distribution, number, and morphological characteristics of cochlear macrophages change significantly across different inner ear regions under various pathological conditions, including noise exposure, ototoxicity, and age-related degeneration. However, the exact mechanism underlying the role of mitochondria in macrophages in auditory function remains unclear. Here, we summarize the major factors and mitochondrial signaling pathways (e.g., metabolism, mitochondrial reactive oxygen species, mitochondrial DNA, and the inflammasome) that influence macrophage activation in the innate immune response. In particular, we focus on the properties of cochlear macrophages, activated signaling pathways, and the secretion of inflammatory cytokines after acoustic injury. We hope this review will provide new perspectives and a basis for future research on cochlear inflammation.


Assuntos
Imunidade Inata , Macrófagos , Humanos , Cóclea/metabolismo , Cóclea/patologia , Inflamação/metabolismo , Mitocôndrias
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