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1.
Food Sci Nutr ; 12(5): 3177-3187, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38726456

RESUMO

The demand for identification of maize varieties has increased dramatically due to the phenomenon of mixed seeds and inferior varieties pretending to be high-quality varieties continuing to occur. It is urgent to solve the problem of efficient and accurate identification of maize varieties. A hyperspectral image acquisition system was used to acquire images of maize seeds. Regions of interest (ROI) with an embryo size of 10 × 10 pixel were extracted, and the average spectral information in the range of 949.43-1709.49 nm was intercepted for the subsequent study in order to eliminate random noise at both ends. Savitzky-Golay (SG) smoothing algorithm and multiple scattering correction (MSC) were used to pretreat the full-band spectrum. The feature wavelengths were screened by successive projection algorithms (SPA), competitive adaptive reweighted sampling (CARS) single screening, and two combinations of CARS-SPA and CARS + SPA, respectively. Support vector machines (SVMs) and models optimized based on genetic algorithm (GA), particle swarm optimization (PSO) were established by using full bands (FB) and feature bands as the model input. The results showed that the MSC-(CARS-SPA)-GA-SVM model had the best performance with 93.00% of the test set accuracy, 8 feature variables, and a running time of 24.45 s. MSC pretreatment can effectively eliminate the scattering effect of spectral data, and the feature wavelengths extracted by CARS-SPA can represent all wavelength information. The study proved that hyperspectral imaging combined with GA-SVM can realize the identification of maize varieties, which provided a theoretical basis for maize variety classification and authenticity identification.

2.
Biomark Res ; 12(1): 48, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38730450

RESUMO

BACKGROUND: Tumors exhibit metabolic heterogeneity, influencing cancer progression. However, understanding metabolic diversity in retinoblastoma (RB), the primary intraocular malignancy in children, remains limited. METHODS: The metabolic landscape of RB was constructed based on single-cell transcriptomic sequencing from 11 RB and 5 retina samples. Various analyses were conducted, including assessing overall metabolic activity, metabolic heterogeneity, and the correlation between hypoxia and metabolic pathways. Additionally, the expression pattern of the monocarboxylate transporter (MCT) family in different cell clusters was examined. Validation assays of MCT1 expression and function in RB cell lines were performed. The therapeutic potential of targeting MCT1 was evaluated using an orthotopic xenograft model. A cohort of 47 RB patients was analyzed to evaluate the relationship between MCT1 expression and tumor invasion. RESULTS: Distinct metabolic patterns in RB cells, notably increased glycolysis, were identified. This metabolic heterogeneity correlated closely with hypoxia. MCT1 emerged as the primary monocarboxylate transporter in RB cells. Disrupting MCT1 altered cell viability and energy metabolism. In vivo studies using the MCT1 inhibitor AZD3965 effectively suppressed RB tumor growth. Additionally, a correlation between MCT1 expression and optic nerve invasion in RB samples suggested prognostic implications. CONCLUSIONS: This study enhances our understanding of RB metabolic characteristics at the single-cell level, highlighting the significance of MCT1 in RB pathogenesis. Targeting MCT1 holds promise as a therapeutic strategy for combating RB, with potential prognostic implications.

3.
Food Chem ; 452: 139542, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38728898

RESUMO

This study investigated the effects of ethanol, 1,2-propanediol, and glycerol on the structure and aggregation behavior of silver carp (Hypophthalmichthys molitrix) myosin. All alcohols induced extensive alteration in the tertiary structure of myosin. Both ethanol and 1,2-propanediol further promoted an increase in the content of ß-sheets in myosin and induced myosin aggregation. While glycerol had almost no impact on the secondary structure of myosin. Molecular dynamics simulations revealed that increasing the concentration of ethanol and 1,2-propanediol affected the overall structural changes in the myosin heavy chain (MHC), while glycerol exerted a more pronounced effect on the MHC tail when compared to the MHC head. Disruption of the hydration layers induced by ethanol and 1,2-propanediol contributed to local structural changes in myosin. Glycerol at a concentration of 20% induced the formation of a larger hydration layer around the MHC tail, which facilitated the stabilization of the protein structure.

4.
Phytomedicine ; 129: 155700, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38704914

RESUMO

BACKGROUND: Myoglobin (Mb) induced death of renal tubular epithelial cells (RTECs) is a major pathological factor in crush syndrome-related acute kidney injury (CS-AKI). It is unclear whether ferroptosis is involved and could be a target for treatment. PURPOSE: This study aimed to evaluate the potential therapeutic effects of combining the natural small molecule rosemarinic acid (RA) and the iron chelator deferasirox (Dfe) on CS-AKI through inhibition of ferroptosis. METHODS: Sequencing data were downloaded from the GEO database, and differential expression analysis was performed using the R software limma package. The CS-AKI mouse model was constructed by squeezing the bilateral thighs of mice for 16 h with 1.5 kg weight. TCMK1 and NRK-52E cells were induced with 200 µM Mb and then treated with RA combined with Dfe (Dfe + RA, both were 10 µM). Functional and pathological changes in mouse kidney were evaluated by glomerular filtration rate (GFR) and HE pathology. Immunofluorescence assay was used to detect Mb levels in kidney tissues. The expression levels of ACSL4, GPX4, Keap1, and Nrf2 were analyzed by WB. RESULTS: We found that AKI mice in the GSE44925 cohort highly expressed the ferroptosis markers ACSL4 and PTGS2. CS-AKI mice showed a rapid decrease in GFR, up-regulation of ACSL4 expression in kidney tissue, and down-regulation of GPX4 expression, indicating activation of the ferroptosis pathway. Mb was found to deposit in renal tubules, and it has been proven to cause ferroptosis in TCMK1 and NRK-52E cells in vitro. We found that Dfe had a strong iron ion scavenging effect and inhibited ACSL4 expression. RA could disrupt the interaction between Keap1 andNrf2, stabilize Nrf2, and promote its nuclear translocation, thereby exerting antioxidant effects. The combination of Dfe and RA effectively reversed Mb induced ferroptosis in RTECs. CONCLUSION: In conclusion, we found that RA combined with Dfe attenuated CS-AKI by inhibiting Mb-induced ferroptosis in RTECs via activating the Nrf2/Keap1 pathway.

5.
Plants (Basel) ; 13(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38732433

RESUMO

Grain size has an important effect on rice yield. Although several key genes that regulate seed size have been reported in rice, their molecular mechanisms remain unclear. In this study, a rice small grain size 2 (sms2) mutant was identified, and MutMap resequencing analysis results showed that a 2 bp insertion in the second exon of the LOC_Os02g01590 gene resulted in a grain length and width lower than those of the wild-type Teqing (TQ). We found that SMS2 encoded vacuolar acid invertase, a novel allele of OsINV3, which regulates grain size. GO and KEGG enrichment analyses showed that SMS2 was involved in endoplasmic reticulum protein synthesis, cysteine and methionine metabolism, and propionic acid metabolism, thereby regulating grain size. An analysis of sugar content in young panicles showed that SMS2 reduced sucrose, fructose, and starch contents, thus regulating grain size. A haplotype analysis showed that Hap2 of SMS2 had a longer grain and was widely present in indica rice varieties. Our results provide a new theoretical basis for the molecular and physiological mechanisms by which SMS2 regulates grain size.

6.
Small ; : e2402310, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38726774

RESUMO

Solar energy, as a renewable energy source, dominates the vast majority of human energy, which can be harvested and converted by photovoltaic solar cells. However, the intermittent availability of solar energy restricts the actual utilization circumstances of solar cells. Integrating photo-responsive electrodes into an energy storage device emerges as a dependable and executable strategy, fostering the creation of photo-stimulated batteries that seamlessly amalgamate the process of solar energy collection, conversion, and storage in one system. Endowed by virtues such as cost-effectiveness, facile manufacturing, safety, and environmental friendliness, photo-stimulated Zn-based batteries have attracted considerable attention. The progress report furnishes a brief overview, summarizing various photo-stimulated Zn-based batteries. Their configurations, operational principles, advancements, and the intricate engineering of photoelectrode designs are introduced, respectively. Through rigorous architectural design, photo-stimulated Zn-based batteries exhibit the ability to initiate charging by saving electricity usage, and in certain instances, even without the need for external electrical grids under illumination. Furthermore, the compensation of solar energy can be explored to improve the output electric energy. At last, opportunities and challenges toward photo-stimulated Zn-based batteries in the process of development are proposed and discussed in the hope of expanding their application scenarios and accelerating the commercialization progress.

7.
Mol Biol Rep ; 51(1): 639, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727924

RESUMO

BACKGROUND: Peucedani Radix, also known as "Qian-hu" is a traditional Chinese medicine derived from Peucedanum praeruptorum Dunn. It is widely utilized for treating wind-heat colds and coughs accompanied by excessive phlegm. However, due to morphological similarities, limited resources, and heightened market demand, numerous substitutes and adulterants of Peucedani Radix have emerged within the herbal medicine market. Moreover, Peucedani Radix is typically dried and sliced for sale, rendering traditional identification methods challenging. MATERIALS AND METHODS: We initially examined and compared 104 commercial "Qian-hu" samples from various Chinese medicinal markets and 44 species representing genuine, adulterants or substitutes, utilizing the mini barcode ITS2 region to elucidate the botanical origins of the commercial "Qian-hu". The nucleotide signature specific to Peucedani Radix was subsequently developed by analyzing the polymorphic sites within the aligned ITS2 sequences. RESULTS: The results demonstrated a success rate of 100% and 93.3% for DNA extraction and PCR amplification, respectively. Forty-five samples were authentic "Qian-hu", while the remaining samples were all adulterants, originating from nine distinct species. Peucedani Radix, its substitutes, and adulterants were successfully identified based on the neighbor-joining tree. The 24-bp nucleotide signature (5'-ATTGTCGTACGAATCCTCGTCGTC-3') revealed distinct differences between Peucedani Radix and its common substitutes and adulterants. The newly designed specific primers (PR-F/PR-R) can amplify the nucleotide signature region from commercial samples and processed materials with severe DNA degradation. CONCLUSIONS: We advocate for the utilization of ITS2 and nucleotide signature for the rapid and precise identification of herbal medicines and their adulterants to regulate the Chinese herbal medicine industry.


Assuntos
Código de Barras de DNA Taxonômico , DNA de Plantas , DNA de Plantas/genética , Código de Barras de DNA Taxonômico/métodos , Medicamentos de Ervas Chinesas/normas , Apiaceae/genética , Apiaceae/classificação , Medicina Tradicional Chinesa/normas , DNA Espaçador Ribossômico/genética , Contaminação de Medicamentos , Plantas Medicinais/genética , Filogenia , Análise de Sequência de DNA/métodos , Reação em Cadeia da Polimerase/métodos , Nucleotídeos/genética , Nucleotídeos/análise
8.
Abdom Radiol (NY) ; 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38703189

RESUMO

OBJECTIVES: Differentiating intestinal tuberculosis (ITB) from Crohn's disease (CD) remains a diagnostic dilemma. Misdiagnosis carries potential grave implications. We aim to establish a multidisciplinary-based model using machine learning approach for distinguishing ITB from CD. METHODS: Eighty-two patients including 25 patients with ITB and 57 patients with CD were retrospectively recruited (54 in training cohort and 28 in testing cohort). The region of interest (ROI) for the lesion was delineated on magnetic resonance enterography (MRE) and colonoscopy images. Radiomic features were extracted by least absolute shrinkage and selection operator regression. Pathological feature was extracted automatically by deep-learning method. Clinical features were filtered by logistic regression analysis. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Delong's test was applied to compare the efficiency between the multidisciplinary-based model and the other four single-disciplinary-based models. RESULTS: The radiomics model based on MRE features yielded an AUC of 0.87 (95% confidence interval [CI] 0.68-0.96) on the test data set, which was similar to the clinical model (AUC, 0.90 [95% CI 0.71-0.98]) and higher than the colonoscopy radiomics model (AUC, 0.68 [95% CI 0.48-0.84]) and pathology deep-learning model (AUC, 0.70 [95% CI 0.49-0.85]). Multidisciplinary model, integrating 3 clinical, 21 MRE radiomic, 5 colonoscopy radiomic, and 4 pathology deep-learning features, could significantly improve the diagnostic performance (AUC of 0.94, 95% CI 0.78-1.00) on the bases of single-disciplinary-based models. DCA confirmed the clinical utility. CONCLUSIONS: Multidisciplinary-based model integrating clinical, MRE, colonoscopy, and pathology features was useful in distinguishing ITB from CD.

9.
Science ; 384(6695): 557-563, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38696573

RESUMO

Hydrogels are an attractive category of biointerfacing materials with adjustable mechanical properties, diverse biochemical functions, and good ionic conductivity. Despite these advantages, their application in electronics has been restricted because of their lack of semiconducting properties, and they have traditionally only served as insulators or conductors. We developed single- and multiple-network hydrogels based on a water-soluble n-type semiconducting polymer, endowing conventional hydrogels with semiconducting capabilities. These hydrogels show good electron mobilities and high on/off ratios, enabling the fabrication of complementary logic circuits and signal amplifiers with low power consumption and high gains. We demonstrate that hydrogel electronics with good bioadhesive and biocompatible interface can sense and amplify electrophysiological signals with enhanced signal-to-noise ratios.

10.
J Invertebr Pathol ; 204: 108122, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710321

RESUMO

The Asian citrus psyllid (ACP) Diaphorina citri transmits the causative agent of huanglongbing, or citrus greening disease, that has decimated global citrus production. Pesticidal proteins derived from bacteria such as Bacillus thuringiensis (Bt) can provide effective and environmentally friendly alternatives for management of D. citri, but few with sufficient toxicity to D. citri have been identified. Here, we report on the toxicity of 14 Bt-derived pesticidal proteins from five different structural groups against D. citri. These proteins were selected based on previously reported toxicity to other hemipteran species and on pesticidal protein availability. Most of the proteins were expressed in Escherichia coli and purified from inclusion bodies or His-tag affinity purification, while App6Aa2 was expressed in Bt and purified from spore/crystal mixtures. Pesticidal proteins were initially screened by feeding psyllids on a single dose, and lethal concentration (LC50) then determined for proteins with significantly greater mortality than the buffer control. The impact of CLas infection of D. citri on toxicity was assessed for selected proteins via topical feeding. The Bt protein Tpp78Aa1 was toxic to D. citri adults with an LC50 of approximately 204 µg/mL. Nymphs were more susceptible to Tpp78Aa1 than adults but no significant difference in susceptibility was observed between healthy and CLas-infected nymphs or adults. Tpp78Aa1 and other reported D. citri-active proteins may provide valuable tools for suppression of D. citri populations.

11.
Sci Total Environ ; 927: 172169, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38582126

RESUMO

A large amount of metal tailings causes many environmental issues. Thus, the techniques for their ecological restoration have garnered extensive attention. However, they are still in the exploratory stage. Biological soil crusts (BSCs) are a coherent layer comprising photoautotrophic organisms, heterotrophic organisms and soil particles. They are crucial in global terrestrial ecosystems and play an equal importance in metal tailings. We summarized the existing knowledge on BSCs growing on metal tailings. The main photosynthetic organisms (cyanobacteria, eukaryotic algae, lichens, and mosses) of BSCs exhibit a high heavy metal(loid) (HM) tolerance. BSCs also have a strong adaptability to other adverse conditions in tailings, such as poor structure, acidification, and infertility. The literature about tailing BSCs has been rapidly increasing, particularly after 2022. The extensive literature confirms that the BSCs distributed on metal tailings, including all major types of metal tailings in different climatic regisions, are common. BSCs perform various ecological functions in tailings, including HM stress reduction, soil structure improvement, soil nutrient increase, biogeochemical cycle enhancement, and microbial community restoration. They interact and accelerate revegetation of tailings (at least in the temperate zone) and soil formation. Restoring tailings by accelerating/inducing BSC formation (e.g., resource augmentation and inoculation) has also attracted attention and achieved small-scale on-site application. However, some knowledge gaps still exist. The potential areas for further research include the relation between BSCs and HMs, large-scale quantification of tailing BSCs, application of emerging biological techniques, controlled laboratory experiments, and other restoration applications.


Assuntos
Recuperação e Remediação Ambiental , Microbiologia do Solo , Poluentes do Solo , Solo , Solo/química , Poluentes do Solo/análise , Recuperação e Remediação Ambiental/métodos , Metais Pesados/análise , Ecossistema , Metais/análise , Mineração
12.
Foods ; 13(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38611436

RESUMO

The emergence of multi-drug-resistant (MDR) pathogens has considerably challenged the development of new drugs. Probiotics that inhibit MDR pathogens offer advantages over chemical antibiotics and drugs due to their increased safety and fewer side effects. This study reported that Weissella cibaria P-8 isolated from pickles showed excellent antibacterial activity against intestinal pathogens, particularly the antibacterial activity against MDR Escherichia coli B2 was the highest. This study showed that the survival rates of W. cibaria P-8 at pH 2.0 and 0.3% bile salt concentration were 72% and 71.56%, respectively, and it still had antibacterial activity under pepsin, trypsin, protease K, and catalase hydrolysis. Moreover, W. cibaria P-8 inhibits the expression of inflammatory factors interleukin-1ß, tumor necrosis factor-α, and interleukin-6, upregulates the interleukin-10 level, and increases total antioxidant capacity and superoxide dismutase enzyme activity in serum. W. cibaria P-8 also efficiently repairs intestinal damage caused by E. coli infection. The gut microbiota analysis demonstrated that W. cibaria P-8 colonizes the intestine and increases the abundance of some beneficial intestinal microorganisms, particularly Prevotella. In conclusion, W. cibaria P-8 alleviated MDR E. coli-induced intestinal inflammation by regulating inflammatory cytokine and enzyme activity and rebalancing the gut microbiota, which could provide the foundation for subsequent clinical analyses and probiotic product development.

13.
Biomed Opt Express ; 15(4): 2498-2516, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38633068

RESUMO

Comprehensive visualization and accurate extraction of tumor vasculature are essential to study the nature of glioma. Nowadays, tissue clearing technology enables 3D visualization of human glioma vasculature at micron resolution, but current vessel extraction schemes cannot well cope with the extraction of complex tumor vessels with high disruption and irregularity under realistic conditions. Here, we developed a framework, FineVess, based on deep learning to automatically extract glioma vessels in confocal microscope images of cleared human tumor tissues. In the framework, a customized deep learning network, named 3D ResCBAM nnU-Net, was designed to segment the vessels, and a novel pipeline based on preprocessing and post-processing was developed to refine the segmentation results automatically. On the basis of its application to a practical dataset, we showed that the FineVess enabled extraction of variable and incomplete vessels with high accuracy in challenging 3D images, better than other traditional and state-of-the-art schemes. For the extracted vessels, we calculated vascular morphological features including fractal dimension and vascular wall integrity of different tumor grades, and verified the vascular heterogeneity through quantitative analysis.

14.
RSC Adv ; 14(18): 12796-12806, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38645515

RESUMO

Paclitaxel (PTX) remains an essential drug in the treatment of breast cancer. To improve metabolic stability and real-time monitoring of drug location, we develop a visualized nano-prodrug. Novel hyaluronic acid (HA)-coated glutathione (GSH)-sensitive chitosan (CS)-based nano-prodrug (HA/TPE-CS-SS-PTX NPs) with aggregation-induced emission effects (AIE) were accomplished. The prodrug NPs (drug loading 29.32%, particle size 105 nm, regular sphericity) exhibit excellent fluorescence stability. The prodrug NPs could target tumor cells with high expression of CD44 and decompose in the presence of high concentrations of glutathione. In vitro evaluations revealed that the prodrug NPs have significant cytotoxicity on 4T1 cells, and due to their excellent AIE characteristics, their position in cells can be tracked. Moreover, the prodrug NPs also shown superior anti-tumor effects in vivo experimental. Overall, the HA/TPE-CS-SS-PTX NPs we constructed have excellent bio-imaging capabilities and can be served as a potential nanomedicine for PTX delivery against breast cancer.

15.
IEEE Comput Graph Appl ; PP2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38648158

RESUMO

In this paper, we propose TraVis, an interactive system that allows users to explore and analyze complex traffic trajectory data at urban intersections. Trajectory data contains a large amount of spatio-temporal information, and while previous studies have mainly focused on the macroscopic aspects of traffic flow, TraVis employs visualization methods to investigate and analyze microscopic traffic events, i.e., high-value scenes in trajectory data. TraVis contains a novel view design and provides multiple interaction modalities to offer users the most intuitive insights into high-value scenes. With this system, users can gain a better understanding of urban intersection traffic information, identify different types of high-value scenes, explore the reasons behind their occurrence, and gain deeper insights into urban intersection traffic. Through two case studies, we illustrate how to use the system and validate its effectiveness.

16.
J Sci Food Agric ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38572795

RESUMO

BACKGROUND: The present study aimed to investigate the effects of tremella polysaccharides on the gel properties and antioxidant activity of yak skin gelatin with a view to improving the quality of collagen jellies. The preparation of composite gels were performed by yak skin gelatin (66.7 mg mL-1) and tremella polysaccharides with different concentrations (0, 2, 4, 6, 8 mg mL-1), and finally the collagen jelly was prepared by composite gel (yak skin gelatin: 66.7 mg mL-1; tremella polysaccharides:6 mg mL-1) with the best performance. RESULTS: Tremella polysaccharides not only improved the hardness, springiness, gel strength, water holding capacity and melting temperature of yak skin gelatin, but also enhanced the composite gel's scavenging activity against ABTS radicals, DPPH radicals, O2 and OH radicals. The filling of tremella polysaccharides into the gelatin network increased the number of crosslinking sites inside the gel, which resulted in the gel network structure becoming dense and orderly. The gel particles became finer and more uniform, and the thermal stability was improved. Furthermore, the sensory score of commercially available gelatin jelly decreased more rapidly during storage compared to the composite gel jelly. CONCLUSION: The gel properties and antioxidant activity of yak skin gelatin were improved by adding tremella polysaccharides, and then the quality and storage properties of the jelly were improved, which also provided technical reference for the development of functional gel food. © 2024 Society of Chemical Industry.

17.
Brain Sci ; 14(4)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38672017

RESUMO

EEG signals combined with deep learning play an important role in the study of human-computer interaction. However, the limited dataset makes it challenging to study EEG signals using deep learning methods. Inspired by the GAN network in image generation, this paper presents an improved generative adversarial network model L-C-WGAN-GP to generate artificial EEG data to augment training sets and improve the application of BCI in various fields. The generator consists of a long short-term memory (LSTM) network and the discriminator consists of a convolutional neural network (CNN) which uses the gradient penalty-based Wasserstein distance as the loss function in model training. The model can learn the statistical features of EEG signals and generate EEG data that approximate real samples. In addition, the performance of the compressed sensing reconstruction model can be improved by using augmented datasets. Experiments show that, compared with the existing advanced data amplification techniques, the proposed model produces EEG signals closer to the real EEG signals as measured by RMSE, FD and WTD indicators. In addition, in the compressed reconstruction of EEG signals, adding the new data reduces the loss by about 15% compared with the original data, which greatly improves the reconstruction accuracy of the EEG signals' compressed sensing.

18.
Exp Neurol ; : 114802, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38679280

RESUMO

Pyroptosis signifies a significant form of programmed neuronal demise subsequent to ischemic stroke. In our prior investigations, we demonstrated that the Elabela (ELA)-Apelin receptor (APJ) axis alleviated neuronal death by improving collateral circulation and mitigating ferroptosis in a murine model of middle cerebral artery occlusion (MCAO). However, the connection between ELA and neuronal pyroptosis remains further elucidation. Here, we observed an upregulation of ELA and APJ expression in both murine brain specimens and cultured HT-22 hippocampal neurons exposed to experimental ischemic stroke. ELA administration markedly diminished the infarct size in comparison to controls. ELA treatment ameliorated neurological deficits and anxiety-like symptoms in mice with stroke, concurrently inhibiting pyroptosis and mitochondria fission in neurons. Conversely, ELA knockdown yielded the opposite effects. Utilizing RNA-sequencing analysis, we identified a candidate for pyroptosis priming, Z-DNA-binding protein 1 (ZBP1), which was suppressed in ELA-treated HT-22 neurons during oxygen-glucose deprivation/reperfusion (OGD/R). Subsequent co-immunoprecipitation analyses demonstrated the binding between APJ and ZBP1. Specifically, APJ suppressed ZBP1 to inhibit NLRP3 inflammasome activation and dynamin-related protein 1-mediated mitochondrial fission in neurons. In summary, our findings suggest that ELA functions as a stroke-induced signal limiting neuronal pyroptosis and mitochondrial fission via APJ/ZBP1 signaling, thereby underscoring ELA as a potential therapeutic target for ischemic stroke treatment.

19.
Discov Oncol ; 15(1): 107, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38583115

RESUMO

Ferroptosis is a novel form of programmed death, dependent on iron ions and oxidative stress, with a predominant intracellular form of lipid peroxidation. In recent years, ferroptosis has gained more and more interest of people in the treatment mechanism of targeted tumors. mTOR, always overexpressed in the tumor, and controlling cell growth and metabolic activities, has an important role in both autophagy and ferroptosis. Interestingly, the selective types of autophay plays an important role in promoting ferroptosis, which is related to mTOR and some metabolic pathways (especially in iron and amino acids). In this paper, we list the main mechanisms linking ferroptosis with mTOR signaling pathway and further summarize the current compounds targeting ferroptosis in these ways. There are growing experimental evidences that targeting mTOR and ferroptosis may have effective impact in many tumors, and understanding the mechanisms linking mTOR to ferroptosis could provide a potential therapeutic approach for tumor treatment.

20.
Redox Biol ; 72: 103156, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38640584

RESUMO

Regulation of the oxidative stress response is crucial for the management and prognosis of traumatic brain injury (TBI). The copper chaperone Antioxidant 1 (Atox1) plays a crucial role in regulating intracellular copper ion balance and impacting the antioxidant capacity of mitochondria, as well as the oxidative stress state of cells. However, it remains unknown whether Atox1 is involved in modulating oxidative stress following TBI. Here, we investigated the regulatory role of Atox1 in oxidative stress on neurons both in vivo and in vitro, and elucidated the underlying mechanism through culturing hippocampal HT-22 cells with Atox1 mutation. The expression of Atox1 was significantly diminished following TBI, while mice with overexpressed Atox1 exhibited a more preserved hippocampal structure and reduced levels of oxidative stress post-TBI. Furthermore, the mice displayed notable impairments in learning and memory functions after TBI, which were ameliorated by the overexpression of Atox1. In the stretch injury model of HT-22 cells, overexpression of Atox1 mitigated oxidative stress by preserving the normal morphology and network connectivity of mitochondria, as well as facilitating the elimination of damaged mitochondria. Mechanistically, co-immunoprecipitation and mass spectrometry revealed the binding of Atox1 to DJ-1. Knockdown of DJ-1 in HT-22 cells significantly impaired the antioxidant capacity of Atox1. Mutations in the copper-binding motif or sequestration of free copper led to a substantial decrease in the interaction between Atox1 and DJ-1, with overexpression of DJ-1 failing to restore the antioxidant capacity of Atox1 mutants. The findings suggest that DJ-1 mediates the ability of Atox1 to withstand oxidative stress. And targeting Atox1 could be a potential therapeutic approach for addressing post-traumatic neurological dysfunction.


Assuntos
Lesões Encefálicas Traumáticas , Proteínas de Transporte de Cobre , Hipocampo , Mitofagia , Neurônios , Estresse Oxidativo , Proteína Desglicase DJ-1 , Animais , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/genética , Camundongos , Hipocampo/metabolismo , Hipocampo/patologia , Neurônios/metabolismo , Proteína Desglicase DJ-1/metabolismo , Proteína Desglicase DJ-1/genética , Proteínas de Transporte de Cobre/metabolismo , Proteínas de Transporte de Cobre/genética , Mitocôndrias/metabolismo , Modelos Animais de Doenças , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/genética , Masculino , Antioxidantes/metabolismo , Linhagem Celular , Humanos
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