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1.
Nucleic Acids Res ; 51(D1): D199-D207, 2023 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-36321659

RESUMEN

An updated LncTarD 2.0 database provides a comprehensive resource on key lncRNA-target regulations, their influenced functions and lncRNA-mediated regulatory mechanisms in human diseases. LncTarD 2.0 is freely available at (http://bio-bigdata.hrbmu.edu.cn/LncTarD or https://lnctard.bio-database.com/). LncTarD 2.0 was updated with several new features, including (i) an increased number of disease-associated lncRNA entries, where the current release provides 8360 key lncRNA-target regulations, with 419 disease subtypes and 1355 lncRNAs; (ii) predicted 3312 out of 8360 lncRNA-target regulations as potential diagnostic or therapeutic biomarkers in circulating tumor cells (CTCs); (iii) addition of 536 new, experimentally supported lncRNA-target regulations that modulate properties of cancer stem cells; (iv) addition of an experimentally supported clinical application section of 2894 lncRNA-target regulations for potential clinical application. Importantly, LncTarD 2.0 provides RNA-seq/microarray and single-cell web tools for customizable analysis and visualization of lncRNA-target regulations in diseases. RNA-seq/microarray web tool was used to mining lncRNA-target regulations in both disease tissue samples and CTCs blood samples. The single-cell web tools provide single-cell lncRNA-target annotation from the perspectives of pan-cancer analysis and cancer-specific analysis at the single-cell level. LncTarD 2.0 will be a useful resource and mining tool for the investigation of the functions and mechanisms of lncRNA deregulation in human disease.


Asunto(s)
Bases de Datos de Ácidos Nucleicos , ARN Largo no Codificante , Humanos , Manejo de Datos , Bases de Datos Genéticas , Neoplasias/genética , ARN Largo no Codificante/genética , Enfermedad/genética
2.
J Transl Med ; 22(1): 590, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38915053

RESUMEN

Lung cancer is the primary cause of cancer-related death worldwide, and its global incidence and mortality rates remain high. The differential expression of circular RNAs (circRNAs) can affect the development of cancer, but the mechanisms by which circRNAs regulate lung cancer progression remain unclear. In this study, we identified circSORBS1, a circRNA that has not been previously described in lung cancer and is significantly underexpressed in lung cancer tissues, blood and cell lines, and the low expression of circSORBS1 correlated with tumour grade and prognosis. In vitro and in vivo functional experiments revealed that circSORBS1 overexpression inhibited cell proliferation and migration while enhancing apoptosis. Mechanistically, circSORBS1 acts as a sponge for miR-6779-5p, indirectly inhibiting RUFY3 mRNA degradation. Simultaneously, it binds to RUFY3 mRNA to enhance its stability. This dual regulatory mechanism leads to an increase in RUFY3 protein levels, which ultimately activates the YWHAE/BAD/BCL2 apoptotic signalling pathway and suppresses lung cancer progression. Our findings not only increase the knowledge about the regulatory pattern of circRNA expression but also provide new insights into the mechanisms by which circRNAs regulate lung cancer development.


Asunto(s)
Apoptosis , Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , MicroARNs , ARN Circular , ARN Mensajero , Animales , Femenino , Humanos , Masculino , Apoptosis/genética , Secuencia de Bases , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , Estabilidad del ARN/genética , ARN Circular/genética , ARN Circular/metabolismo , ARN Mensajero/metabolismo , ARN Mensajero/genética
3.
Environ Toxicol ; 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39004893

RESUMEN

Trimethyltin chloride (TMT) is a highly toxic organotin pollutant frequently found in aquatic environments, posing a significant threat to the ecological system. The kidney plays a vital role in the body's detoxification processes, and TMT present in the environment tends to accumulate in the kidneys. However, it remained unclear whether exposure to different doses of TMT could induce pyroptosis and immune dysfunction in grass carp kidney cells (CIK cells). For this purpose, after assessing the half-maximal inhibitory concentration (IC50) of TMT on CIK cells, we established a model for exposure of CIK cells at varying concentrations of TMT. CIK cells were treated with various doses of TMT (2.5, 5, 10 µM) for 24 h. Oxidative stress levels were measured using kits and fluorescence methods, whereas the expression of related genes was verified through western blot and quantitative real-time PCR (qRT-PCR). The results indicated that TMT exposure led to oxidative stress, with increased levels of ROS, H2O2, MDA, and GSH, and inhibited activities of T-AOC, SOD, and CAT. It activated the NF-κB pathway, leading to the upregulation of NF-κB p65, NF-κB p50, GSDMD, NLRP3, ASC, and Caspase-1. Furthermore, TMT exposure also resulted in increased expression of cytokines (IL-18, IL-6, IL-2, IL-1ß, and TNF-α) and decreased expression of antimicrobial peptides (LEAP2, HEPC, and ß-defensin). In summary, exposure to TMT induces dose-dependent oxidative stress that activates the NF-κB pathway, leading to pyroptosis and immune dysfunction in grass carp CIK cells.

4.
Fish Shellfish Immunol ; 137: 108772, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37100311

RESUMEN

Glyphosate is an herbicide commonly used worldwide, and its substantial use causes widespread pollution with runoff. However, research on glyphosate toxicity has mostly remained at the embryonic level and existing studies are limited. In the present study, we investigated whether glyphosate can induce autophagy in hepatic L8824 cells by regulating energy metabolism and rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated extracellular signal-regulated kinase (MEK)/extracellular regulated protein kinases (ERK) signaling by activating nitric oxide (NO). First, we selected 0, 50, 200, and 500 µg/mL as the challenge doses, according to the inhibitory concentration of 50% (IC50) of glyphosate. The results showed that glyphosate exposure increased the enzyme activity of inducible nitric oxide synthase (iNOS), which in turn increased the NO content. The activity and expression of enzymes related to energy metabolism, such as hexokinase (HK)1, HK2, phosphofructokinase (PFK), phosphokinase (PK), succinate dehydrogenase (SDH), and nicotinamide adenine dinucleotide with hydrogen (NADH), were inhibited, and the RAS/RAF/MEK/ERK signaling pathway was activated. This led to the negative expression of mammalian target of rapamycin (mTOR) and P62 in hepatic L8824 cells and the activation of the autophagy marker genes microtubule-associated proteins light chain 3 (LC3) and Beclin1 to induce autophagy. The above results were dependent on glyphosate concentration. To verify whether autophagy can be excited by the RAS/RAF/MEK/ERK signaling pathway, we treated L8824 cells with the ERK inhibitor U0126 and found that the autophagy gene LC3 was reduced due to the inhibition of ERK, thus demonstrating the reliability of the results. In conclusion, our results demonstrate that glyphosate can induce autophagy in hepatic L8824 cells by activating NO, thus regulating energy metabolism and the RAS/RAF/MEK/ERK signaling pathway.


Asunto(s)
Fibrosarcoma , Quinasas Quinasa Quinasa PAM , Animales , Óxido Nítrico , Reproducibilidad de los Resultados , Quinasas raf/genética , Transducción de Señal , Quinasas MAP Reguladas por Señal Extracelular , Línea Celular , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Metabolismo Energético , Autofagia , Sistema de Señalización de MAP Quinasas , Mamíferos/metabolismo , Glifosato
5.
Thromb J ; 21(1): 95, 2023 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-37710256

RESUMEN

INTRODUCTION: Venous thromboembolism(VTE) is a leading cause of death in patients with lung cancer. Furthermore, hospitalization of patients with advanced lung cancer for VTE treatment represents a major economic burden on the national public health resources. Therefore, we performed this prospective study to identify clinical biomarkers for the early identification of VTE in lung cancer patients. METHODS: This prospective study enrolled 158 patients with confirmed lung cancer, including 27 who were diagnosed with VTE within six months of the follow-up after lung cancer diagnosis. Multivariate logistic regression analysis was used to evaluate the diagnostic performancese of all the relevant clinical features and laboratory indicators in identifying lung cancer patients with a higher risk of VTE. A novel risk prediction model was constructed consisting of five clinical variables with the best diagnostic performances and was validated using the receiver operation characteristic(ROC) curves. The diagnostic performances of the new risk prediction model was also compared with the Khorana risk score (KRS) and the Padua risk score (PRS). RESULTS: The VTE group of lung cancer patients (n = 27) showed significantly higher serum levels of fibrin degradation products (FDP), D-dimer, thrombomodulin (TM), thrombin-antithrombin-complex (TAT), α2-plasmin inhibitor-plasmin Complex (PIC), and tissue plasminogen activator-plasminogen activator inhibitor complex (t-PAIC) compared to those in the non-VTE group (n = 131). ROC curve analyses showed that the diagnostic efficacy of the new VTE risk prediction model with TM ≥ 9.75 TU/ml, TAT ≥ 2.25ng/ml, t-PAIC ≥ 7.35ng/ml, history of VTE, and ECOG PS score ≥ 2 was superior than the KRS and the PRS in the early identification of lung cancer patients with a higher risk of VTE. CONCLUSIONS: The new risk prediction model showed significantly high diagnostic efficacy in the early identification of lung cancer patients with a high risk of VTE. The diagnostic efficacy of the new risk prediction model was higher than the KRS and the PRS in this cohort of lung cancer patients.

6.
Cell Biol Toxicol ; 38(1): 129-146, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-33656636

RESUMEN

Extensive research confirmed that circRNA can play a regulatory role in various stages of tumors by interacting with various molecules. Identifying the differentially expressed circRNA in bladder cancer and exploring its regulatory mechanism on bladder cancer progression are urgent. In this study, we screened out a circRNA-circGLIS3 with a significant upregulation trend in both bladder cancer tissues and cells. Bioinformatics prediction results showed that circGLIS3 may be involved in multiple tumor-related pathways. Function gain and loss experiments verified circGLIS3 can affect the proliferation, migration, and invasion of bladder cancer cells in vitro. Moreover, silencing circGLIS3 inhibited bladder cancer cell growth in vivo. Subsequent research results indicated circGLIS3 regulated the expression of cyclin D1, a cell cycle-related protein, and cell cycle progression. Mechanically, circGLIS3 upregulates the expression of SKP1 by adsorbing miR-1273f and then promotes cyclin D1 expression, ultimately promoting the proliferation of bladder cancer cells. In summary, our study indicates that circGLIS3 plays an oncogene role in the development of bladder cancer and has potential to be a candidate for bladder cancer.


Asunto(s)
MicroARNs , Neoplasias de la Vejiga Urinaria , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Ciclina D1/genética , Ciclina D1/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , Proteínas Quinasas Asociadas a Fase-S/genética , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo
7.
Nucleic Acids Res ; 48(D1): D118-D126, 2020 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-31713618

RESUMEN

Long non-coding RNAs (lncRNAs) are associated with human diseases. Although lncRNA-disease associations have received significant attention, no online repository is available to collect lncRNA-mediated regulatory mechanisms, key downstream targets, and important biological functions driven by disease-related lncRNAs in human diseases. We thus developed LncTarD (http://biocc.hrbmu.edu.cn/LncTarD/ or http://bio-bigdata.hrbmu.edu.cn/LncTarD), a manually-curated database that provides a comprehensive resource of key lncRNA-target regulations, lncRNA-influenced functions, and lncRNA-mediated regulatory mechanisms in human diseases. LncTarD offers (i) 2822 key lncRNA-target regulations involving 475 lncRNAs and 1039 targets associated with 177 human diseases; (ii) 1613 experimentally-supported functional regulations and 1209 expression associations in human diseases; (iii) important biological functions driven by disease-related lncRNAs in human diseases; (iv) lncRNA-target regulations responsible for drug resistance or sensitivity in human diseases and (v) lncRNA microarray, lncRNA sequence data and transcriptome data of an 11 373 pan-cancer patient cohort from TCGA to help characterize the functional dynamics of these lncRNA-target regulations. LncTarD also provides a user-friendly interface to conveniently browse, search, and download data. LncTarD will be a useful resource platform for the further understanding of functions and molecular mechanisms of lncRNA deregulation in human disease, which will help to identify novel and sensitive biomarkers and therapeutic targets.


Asunto(s)
Biología Computacional/métodos , Bases de Datos Genéticas , Regulación de la Expresión Génica , Genómica/métodos , Interferencia de ARN , ARN Largo no Codificante/genética , Programas Informáticos , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Interfaz Usuario-Computador , Navegador Web
8.
Sensors (Basel) ; 22(16)2022 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-36015751

RESUMEN

The exploitation and utilization of clean energy such as wind and photovoltaic power plays an important role in the reduction in carbon emissions to achieve the goal of "emission peak and carbon neutral", but such a quantity of clean energy accessing the electric system will foster the transition of the electric power system structure. The intelligentization of power equipment will be an inevitable trend of development. High breaking performance, remote control and a digital detection platform of miniature circuit breaker, a protective equipment of a power distribution system, have also been inevitable requirements of the power Iot system. Based on the above, this paper studies three aspects: high-performance AC and DC general switching technology, remote control technology and operation status' digital monitoring. A new DC non-polar breaking technology is proposed, which improves the short circuit breaking ability. An experimental prototype using the above techniques was fabricated and passed the DC 1000 V/10 kA short-circuit breaking test. On the basis of the above, an intelligent circuit breaker is developed, which contains multiple functions: remote switching, real-time temperature detection, energy metering and fault warning. Moreover, a software for digital condition monitoring and remote control is developed. This work has certain theoretical and practical significance for the development of the power Internet of things.

9.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 39(1): 198-206, 2022 Feb 25.
Artículo en Zh | MEDLINE | ID: mdl-35231982

RESUMEN

Brain-computer interaction (BCI) is a transformative human-computer interaction, which aims to bypass the peripheral nerve and muscle system and directly convert the perception, imagery or thinking activities of cranial nerves into actions for further improving the quality of human life. Magnetoencephalogram (MEG) measures the magnetic field generated by the electrical activity of neurons. It has the unique advantages of non-contact measurement, high temporal and spatial resolution, and convenient preparation. It is a new BCI driving signal. MEG-BCI research has important brain science significance and potential application value. So far, few documents have elaborated the key technical issues involved in MEG-BCI. Therefore, this paper focuses on the key technologies of MEG-BCI, and details the signal acquisition technology involved in the practical MEG-BCI system, the design of the MEG-BCI experimental paradigm, the MEG signal analysis and decoding key technology, MEG-BCI neurofeedback technology and its intelligent method. Finally, this paper also discusses the existing problems and future development trends of MEG-BCI. It is hoped that this paper will provide more useful ideas for MEG-BCI innovation research.


Asunto(s)
Interfaces Cerebro-Computador , Magnetoencefalografía , Encéfalo/fisiología , Electroencefalografía , Humanos , Imágenes en Psicoterapia , Tecnología
10.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 39(2): 405-415, 2022 Apr 25.
Artículo en Zh | MEDLINE | ID: mdl-35523563

RESUMEN

Brain-computer interface (BCI) is a revolutionary human-computer interaction technology, which includes both BCI that can output instructions directly from the brain to external devices or machines without relying on the peripheral nerve and muscle system, and BCI that bypasses the peripheral nerve and muscle system and inputs electrical, magnetic, acoustic and optical stimuli or neural feedback directly to the brain from external devices or machines. With the development of BCI technology, it has potential application not only in medical field, but also in non-medical fields, such as education, military, finance, entertainment, smart home and so on. At present, there is little literature on the relevant application of BCI technology, the current situation of BCI industrialization at home and abroad and its commercial value. Therefore, this paper expounds and discusses the above contents, which are expected to provide valuable information for the public and organizations, BCI researchers, BCI industry translators and salespeople, and improve the cognitive level of BCI technology, further promote the application and industrial transformation of BCI technology and enhance the commercial value of BCI, so as to serve mankind better.


Asunto(s)
Interfaces Cerebro-Computador , Encéfalo/fisiología , Electroencefalografía , Humanos , Tecnología , Interfaz Usuario-Computador
11.
ISA Trans ; 148: 182-190, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38548503

RESUMEN

In this paper we focus on the distributed cyber attack detection and physical fault diagnosis problem for a class of interconnected large-scale systems (ILSSs). In the proposed scheme, apart from node measurement, edge measurement is also used to construct distributed Kalman filter to estimate the state of each subsystem. The gain matrices of Kalman filter are determined by minimizing the covariance of estimation error in the attack-free and fault-free case, which reduces the false alarm rate of cyber attack detection and physical fault diagnosis. Based on this filter, a bank of adjacent residual generators is constructed to characterize the influence of cyber attack on the edge measurement, and the Chi-square test is used to detect whether the received edge measurements are attacked. At the same time, a local residual generator is constructed for each subsystem to characterize the influence of physical faults on it, and the residual signal is evaluated by variance and directional residual, so as to make distributed fault detection and isolation of each subsystem. It is worth noting that at each step, each subsystem first performs attack detection on the received edge measurements, and then estimates its own state using the attack-free edge measurements and node measurement, which further improves the accuracy of fault detection and isolation. In addition, a sufficient condition that ensuring the mean square exponential boundedness of the estimation error is given. Finally, the proposed scheme is verified by an illustrative example.

12.
Mater Today Bio ; 26: 101028, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38590985

RESUMEN

The expansion applications of semiconducting polymer dots (Pdots) among optical nanomaterial field have long posed a challenge for researchers, promoting their intelligent application in multifunctional nano-imaging systems and integrated nanomedicine carriers for diagnosis and treatment. Despite notable progress, several inadequacies still persist in the field of Pdots, including the development of simplified near-infrared (NIR) optical nanoprobes, elucidation of their inherent biological behavior, and integration of information processing and nanotechnology into biomedical applications. This review aims to comprehensively elucidate the current status of Pdots as a classical nanophotonic material by discussing its advantages and limitations in terms of biocompatibility, adaptability to microenvironments in vivo, etc. Multifunctional integration and surface chemistry play crucial roles in realizing the intelligent application of Pdots. Information visualization based on their optical and physicochemical properties is pivotal for achieving detection, sensing, and labeling probes. Therefore, we have refined the underlying mechanisms and constructed multiple comprehensive original mechanism summaries to establish a benchmark. Additionally, we have explored the cross-linking interactions between Pdots and nanomedicine, potential yet complete biological metabolic pathways, future research directions, and innovative solutions for integrating diagnosis and treatment strategies. This review presents the possible expectations and valuable insights for advancing Pdots, specifically from chemical, medical, and photophysical practitioners' standpoints.

13.
Transl Res ; 270: 52-65, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38552953

RESUMEN

The transcribed ultraconserved region (T-UCR) belongs to a new type of lncRNAs that are conserved in homologous regions of the rat, mouse and human genomes. A lot of research has reported that differential expression of T-UCRs can influence the development of various cancers, revealing the ability of T-UCRs as new therapeutic targets or potential cancer biomarkers. Most studies on the molecular mechanisms of T-UCRs in cancer have focused on ceRNA regulatory networks and interactions with target proteins, but the present study reveals an innovative dual-targeted regulatory approach in which T-UCRs bind directly to mRNAs and directly to proteins. We screened T-UCRs that may be related to colorectal cancer (CRC) by performing a whole-genome T-UCR gene microarray and further studied the functional mechanism of T-UCR uc.285+ in the development of CRC. Modulation of uc.285+ affected the proliferation of CRC cell lines and influenced the expression of the CDC42 gene. We also found that uc.285+ promoted the proliferation of CRC cells by directly binding to CDC42 mRNA and enhancing its stability while directly binding to CDC42 protein and affecting its stability. In short, our research on the characteristics of cell proliferation found that uc.285+ has a biological function in promoting CRC proliferation. uc.285+ may have considerable potential as a new diagnostic biomarker for CRC.


Asunto(s)
Proliferación Celular , Neoplasias Colorrectales , ARN Mensajero , Proteína de Unión al GTP cdc42 , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteína de Unión al GTP cdc42/metabolismo , Proteína de Unión al GTP cdc42/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Unión Proteica , ARN no Traducido/genética , ARN no Traducido/metabolismo
14.
Carbohydr Polym ; 334: 122034, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38553233

RESUMEN

Cryogels that are constructed with cellulose nanofibrils (CNF) are important as green materials for a wide range of applications. However, their utilization is limited by inherent hydrophilicity and insufficient mechanical properties. Herein, a processable CNF/nanochitin (NCh)-stabilized Pickering emulsion that contains polylactide (PLA) in the oil phase is developed to directly produce ternary composite cryogels via freeze-drying. The complexation of CNF with NCh promotes CNF adsorption at the surface of PLA droplets, resulting in formation of uniform Pickering PLA droplets. The CNF/NCh complex-stabilized PLA droplets are easy to be translated to the internal structure of the cryogels, exhibiting lightweight nature and possessing highly porous structure. The interconnected network and lamellar structure formed by the CNF/NCh complexes, associating with inclusion of PLA particles, improve the cryogel structure integrity upon post-processing and endow hydrophilic cryogel with water resistance. This study offers a straightforward and eco-friendly Pickering emulsion template on fabrication of the CNF-based composite cryogel with controllable microstructure and mechanical performance, broadening construction of nanocellulose-based composites.

15.
Food Chem X ; 21: 101223, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38384682

RESUMEN

To improve the delightful flavor of mulberry wine through semi-artificial inoculation fermentation with Saccharomyces cerevisiae, we studied the dynamics change of microbiota, along with the physicochemical properties and metabolite profiles and their interaction relationship during the fermentation process. The abundance of lactic acid bacteria (Weissella, Lactobacillus, Fructobacillus, and Pediococcus) increased significantly during fermentation, while yeasts gradually established dominance. The inter-kingdom network of the dominant genera analysis further identified the following as core microbiota: Alternaria, Botrytis, Kazachstania, Acremonium, Mycosphaerella, Pediococcus, Gardnerella, and Schizothecium. Additionally, pH, alcohol, and total acid were significantly affected by microbiota variation. Fourteen of all identified volatile compounds with key different aromas were screened using PCA, OPLS-DA, and rOAV. The network of interconnected core microbiota with key different aromas revealed that Kazachstania and Pediococcus had stronger correlations with 1-butanol, 3-methyl-, propanoic acid, and 2-methyl-ethyl ester.

16.
Phytomedicine ; 128: 155412, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38579666

RESUMEN

BACKGROUND: Psoriasis is a long-lasting, inflammatory, continuous illness caused through T cells and characterized mainly by abnormal growth and division of keratinocytes. Currently, corticosteroids are the preferred option. However, prolonged use of traditional topical medication can lead to adverse reactions and relapse, presenting a significant therapeutic obstacle. Improved alternative treatment options are urgently required. Formononetin (FMN) is a representative component of isoflavones in Huangqi (HQ) [Astragalus membranaceus (Fisch.) Bge.]. It possesses properties that reduce inflammation, combat oxidation, inhibit tumor growth, and mimic estrogen. Although FMN has been shown to ameliorate skin barrier devastation via regulating keratinocyte apoptosis and proliferation, there are no reports of its effectiveness in treating psoriasis. OBJECTIVE: Through transcriptomics clues and experimental investigation, we aimed to elucidate the fundamental mechanisms underlying FMN's action on psoriasis. MATERIALS AND METHODS: Cell viability was examined using CCK8 assay in this study. The results of analysis of differentially expressed genes (DEGs) between FMN-treated HaCaT cells and normal HaCaT cells using RNA-sequencing (RNA-seq) were presented on volcano plots and heatmap. Enrichment analysis was conducted on DEGs using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), and results were validated through RT-qPCR verification. After 12 days of FMN treatment in psoriasis mouse model, we gauged the PASI score and epidermis thickness. A variety of techniques were used to assess FMN's effectiveness on inhibiting inflammation and proliferation related to psoriasis, including RT-qPCR, HE staining, western blot, and immunohistochemistry (IHC). RESULTS: The findings indicated that FMN could suppress the growth of HaCaT cells using CCK8 assay (with IC50 = 40.64 uM) and 20 uM FMN could reduce the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to the greatest extent. FMN-treated HaCaT cells exhibited 985 up-regulated and 855 down-regulated DEGs compared to normal HaCaT cells. GO analysis revealed that DEGs were linked to interferon (IFN) signaling pathway. Furthermore, FMN improved pathological features, which encompassed decreased erythema, scale, and thickness scores of skin lesions in psoriasis mouse model. In vivo experiments confirmed that FMN down-regulated expression of IFN-α, IFN-ß, IFN-γ, decreased secretion of TNF-α and IL-17 inflammatory factors, inhibited expression of IFN-related chemokines included Cxcl9, Cxcl10, Cxcl11 and Cxcr3 and reduced expression of transcription factors p-STAT1, p-STAT3 and IFN regulatory factor 1 (IRF1) in the imiquimod (IMQ) group. CONCLUSIONS: In summary, these results suggested that FMN played an anti-inflammatory and anti-proliferative role in alleviating psoriasis by inhibiting IFN signaling pathway, and FMN could be used as a potential therapeutic agent.


Asunto(s)
Células HaCaT , Isoflavonas , Psoriasis , Transducción de Señal , Isoflavonas/farmacología , Psoriasis/tratamiento farmacológico , Animales , Transducción de Señal/efectos de los fármacos , Humanos , Ratones , Interferones , Supervivencia Celular/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Inflamación/tratamiento farmacológico , Astragalus propinquus/química , Ratones Endogámicos BALB C , Masculino , Modelos Animales de Enfermedad
17.
ISA Trans ; 138: 329-340, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36941136

RESUMEN

This paper concerns the problem of designing distributed control law for a class nonlinear system in which the measurement outputs of the system are distributed in different subsystems. It leads to a challenge that the states of the original systems cannot be completely reconstructed by any single subsystem. In order to solve this problem, distributed state observers and the distributed observer-based distributed control problem emerges as the times require. However, the distributed observers problem of the nonlinear systems is rarely studied, and the distributed control law formed by distributed nonlinear observers has hardly ever been studied up to now. To this end, this paper develops the distributed high-gain observers for a class of nonlinear systems. Unlike the previous several results, our study has the ability to deal with model uncertainty, and devotes itself to overcoming the problem that the separation principle is not tenable. In addition, based on the state estimate generated by the designed distributed observer, an output feedback control law formed by applying the state estimate is developed. Furthermore, a class of sufficient conditions is proved for guaranteeing the error dynamics of the distributed observer and the state trajectory of the closed-loop system to enter an arbitrary small invariant set around the origin. Finally, the simulation results verify the effectiveness of the proposed method.

18.
IEEE Trans Cybern ; 53(2): 913-926, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35969557

RESUMEN

This article proposes an observer-based reinforcement learning (RL) control approach to address the optimal attitude-tracking problem and application for hypersonic vehicles in the reentry phase. Due to the unknown uncertainty and nonlinearity caused by parameter perturbation and external disturbance, accurate model information of hypersonic vehicles in the reentry phase is generally unavailable. For this reason, a novel synchronous estimation is proposed to construct a composite observer for hypersonic vehicles, which consists of a neural-network (NN)-based Luenberger-type observer and a synchronous disturbance observer. This solves the identification problem of nonlinear dynamics in the reference control and realizes the estimation of the system state when unknown nonlinear dynamics and unknown disturbance exist at the same time. By synthesizing the information from the composite observer, an RL tracking controller is developed to solve the optimal attitude-tracking control problem. To improve the convergence performance of critic network weights, concurrent learning is employed to replace the traditional persistent excitation condition with a historical experience replay manner. In addition, this article proves that the weight estimation error is bounded when the learning rate satisfies the given sufficient condition. Finally, the numerical simulation demonstrates the effectiveness and superiority of the proposed approaches to attitude-tracking control systems for hypersonic vehicles.

19.
ACS Omega ; 8(6): 5995-6008, 2023 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-36816673

RESUMEN

As an effective enhanced oil recovery (EOR) method in the late stage of the steam injection process, in situ combustion (ISC) has been verified by more and more researchers owing to its high recovery efficiency and low operation cost. However, the ISC process is prone to bringing about an unfavorable result with a low sweep efficiency and even an extinction process due to the complexity and uncertainty in oil and water distribution as well as the heterogeneity of the actual reservoir. In this work, combustion tube experiments combined with numerical simulations by CMG-STARS were conducted to study the influence of a reservoir's physical parameters on the stability of ISC. It was found that the sustainability of the combustion process is sensitive to permeability and oil saturation, the lower limits of which are determined as 0.2 µm2 and 0.2, respectively. Then, a formula was preliminarily proposed as 0.25 ≤ So/K ≤ 0.8, which could be used as a reference of screening criteria in designing the ISC process.

20.
Biomater Sci ; 11(24): 7867-7883, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37902572

RESUMEN

In vitro culture of organoids holds considerable promise for the treatment of diseases or the provision of artificial organs. Traditional 2D differentiation from mesenchymal stem cells (MSCs) faces challenges in replicating the development of embryonic organs at the cellular level; conversely, the cultivation of 3D organoids exhibits potential for application. It is crucial for clinicians and technology researchers to acquire insights into organoid tissue differentiation, autonomous morphogenesis, as well as 3D assembly processes in vitro. In this investigation, novel 3D organoids capable of engendering complex liver-like tissues in vitro were cultured, and a class of high-luminance semiconductor polymer dots (Pdots) was employed to monitor the self-assembly process of 3D liver organoid tissues and cellular interaction and migration dynamics. Three-dimensional liver-bud (3D-LB) organoid tissues were derived through the interplay of induced MSCs, Wharton's Jelly, and human umbilical vein endothelial cells (HUVECs), and their structural characteristics were determined during the liver-bud organoid development; ultimately, the co-cultured organoid spatial cellular clusters resembling a truffle were successfully replicated. Utilizing R8-Pdots with remarkable resolution and biocompatibility, the structural elements of functional and vascularized organs derived from liver organoid tissues were adeptly reconstituted, and this investigation shall contribute to a further understanding of human hepato-developmental physiology and liver-disease modeling.


Asunto(s)
Hígado , Organoides , Humanos , Células Endoteliales de la Vena Umbilical Humana , Técnicas de Cocultivo , Diferenciación Celular
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